{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:53:34Z","timestamp":1791896014889,"version":"4.3.4"},"update-to":[{"DOI":"10.12688\/f1000research.155021.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000}}],"reference-count":132,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Abstract* Background Understanding the demographics, tumor characteristics, mutations, and immune scores in colorectal cancer (CRC) patients may aid in tailoring treatment and predicting survival. Methods This retrospective cohort study assessed clinical parameters, immune scores, and their relationship with survival in patients with CRC. Results The study included 74 patients, mean age 53.7 years, mostly male (53.3%) and aged 41-70 (77.3%). Common comorbidities included cardiovascular diseases (29.3%) and hypertension (21.3%). Adenocarcinoma accounts for 74% of CRC cases, with 73% of CRCs affecting the colon. KRAS mutations and Microsatellite instability-High (MSI-H)\/deficient mismatch repair (dMMR) were found in 1.3% and 16% of patients, respectively. Stage IV (77.3%) and liver metastases (52.7%) were prevalent. Immune score was influenced by cancer stage (p = 0.04) and metastasis (p=0.05). The immune score was not associated with survival (p = 0.181). Patients with comorbidities had lower one- (p = 0.027) and two-year survival rates (p = 0.037) survival rates. Cardiovascular comorbidities negatively impacted one-year survival (p = 0.047) and two-year survival (p = 0.037). The mean survival time was shorter for males (2.047\u00b10.288 vs. 2.781\u00b10.195 years, p = 0.041), patients with comorbidities (1.772\u00b10.371 vs. 2.702\u00b10.188 years, p = 0.017), and cardiovascular comorbidities (1.558\u00b10.316 vs. 2.685\u00b10.207 years, p = 0.038). Comorbidities (unadjusted hazard ratio [HR] 2.948, p = 0.023) and cardiovascular comorbidities (unadjusted HR 2.695, p = 0.046) were initially associated with survival but lost significance after adjusting for confounding variables. Conclusions This study provides insights into CRC patient demographics and their interplay with the immune score and survival.<\/ns3:p>","DOI":"10.12688\/f1000research.155021.2","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:39:06Z","timestamp":1776339546000},"page":"1362","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The Demographic Profile of Colorectal Cancer Patients in Indonesia: Insights from a Single Center Experience and Exploration of Immune Response and Survival Outcomes"],"prefix":"10.12688","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-3219","authenticated-orcid":false,"given":"Cosphiadi","family":"Irawan","sequence":"first","affiliation":[{"name":"Jakarta 10430 Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Findy","family":"Prasetyawaty","sequence":"additional","affiliation":[{"name":"Jakarta 10430 Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"209-249","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e0227294","DOI":"10.1371\/journal.pone.0227294","article-title":"Evaluation of KRAS, NRAS, and BRAF mutation detection in plasma using an automated system in patients with metastatic colorectal cancer.","volume":"15","author":"C Franczak","year":"2020","journal-title":"PLoS One."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12935-019-1091-8","article-title":"Microsatellite instability: a review of what the oncologist should know.","volume":"20","author":"K Li","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1789032","DOI":"10.1080\/2162402X.2020.1789032","article-title":"The consensus immunoscore is toward a new classification of colorectal cancer.","volume":"9","author":"A Lanzi","year":"2020","journal-title":"Onco Targets Ther."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2128-2139","DOI":"10.1016\/S0140-6736(18)30789-X","article-title":"International validation of the consensus immunoscore for the classification of colon cancer: a prognostic and accuracy study.","volume":"391","author":"F Pag\u00e8s","year":"2018","journal-title":"Lancet."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"152-161","DOI":"10.23736\/S1824-4785.20.03249-5","article-title":"Immunoscore and its introduction in clinical practice.","volume":"64","author":"J Galon","year":"2020","journal-title":"Q. J. Nucl. Med. Mol. Imaging."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.3390\/cancers13061281","article-title":"Therapeutic implications of immunoscore in patients with colorectal cancer.","volume":"13","author":"C El Sissy","year":"2021","journal-title":"Cancers (Basel)."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s40425-016-0161-x","article-title":"Biomarkers immune monitoring technology primer: Immunoscore\u00ae colon.","volume":"4","author":"F Hermitte","year":"2016","journal-title":"J. Immunother. Cancer."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"233-254","DOI":"10.3322\/caac.21772","article-title":"Colorectal cancer statistics, 2023.","volume":"73","author":"R Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"89-103","DOI":"10.5114\/pg.2018.81072","article-title":"Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors.","volume":"14","author":"P Rawla","year":"2019","journal-title":"Prz Gastroenterol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"338-344","DOI":"10.1136\/gutjnl-2022-327736","article-title":"Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN.","volume":"72","author":"E Morgan","year":"2023","journal-title":"Gut."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"101174","DOI":"10.1016\/j.tranon.2021.101174","article-title":"Global colorectal cancer burden in 2020 and projections to 2040.","volume":"14","author":"Y Xi","year":"2021","journal-title":"Transl Oncol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1110-1115","DOI":"10.1200\/GO.21.00111","article-title":"Colorectal cancers in low- and middle-income countries-demographic pattern and clinical profile of 970 patients treated at a tertiary care cancer center in India.","volume":"7","author":"S Deo","year":"2021","journal-title":"JCO Glob. Oncol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"100705","DOI":"10.1016\/j.ctarc.2023.100705","article-title":"Challenges in the management of colorectal cancer in low- and middle-income countries.","volume":"35","author":"S Khan","year":"2023","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"663-671","DOI":"10.1093\/jn\/nxz268","article-title":"World Cancer Research Fund\/American Institute for Cancer Research third expert report on diet, nutrition, physical activity, and cancer: impact and future directions.","volume":"150","author":"S Clinton","year":"2020","journal-title":"J. Nutr."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1-8","DOI":"10.26633\/RPSP.2019.3","article-title":"Early-life obesity and adult colorectal cancer risk: a meta-analysis.","volume":"43","author":"H Garcia","year":"2019","journal-title":"Rev. Panam. Salud Publica."},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20170945","article-title":"Abdominal obesity and colorectal cancer risk: a systematic review and meta-analysis of prospective studies.","volume":"37","author":"Y Dong","year":"2017","journal-title":"Biosci. Rep."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e0120706","DOI":"10.1371\/journal.pone.0120706","article-title":"Association between body mass index and prognosis of colorectal cancer: a meta-analysis of prospective cohort studies.","volume":"10","author":"J Lee","year":"2015","journal-title":"PLoS One."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1217-1229","DOI":"10.1093\/annonc\/mdx080","article-title":"Adult weight gain and colorectal adenocarcinoma: A systematic review and meta-analysis.","volume":"28","author":"S Schlesinger","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2880-2889","DOI":"10.1002\/ijc.29331","article-title":"Association between adult weight gain and colorectal cancer: a dose-response meta-analysis of observational studies.","volume":"136","author":"Q Chen","year":"2015","journal-title":"Int. J. Cancer."},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061408","article-title":"Linking obesity with colorectal cancer: epidemiology and mechanistic insights.","volume":"12","author":"P Ye","year":"2020","journal-title":"Cancers (Basel)."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"143-152","DOI":"10.5223\/pghn.2013.16.3.143","article-title":"Obesity, inflammation and diet.","volume":"16","author":"H Lee","year":"2013","journal-title":"Pediatr Gastroenterol. Hepatol. Nutr."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"138-148","DOI":"10.1016\/j.bbcan.2017.12.002","article-title":"Colorectal cancer prevention: immune modulation taking the stage.","volume":"1869","author":"R Fletcher","year":"2018","journal-title":"Biochim. Biophys. Acta Rev. Cancer."},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12040923","article-title":"Ex vivo organoid cultures reveal the importance of the tumor microenvironment in the maintenance of colorectal cancer stem cells.","volume":"12","author":"X Li","year":"2020","journal-title":"Cancers (Basel)."},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.23889\/ijpds.v5i5.1429","article-title":"Identifying patterns of comorbidities with cancers of the colon and rectum as related to age at diagnosis.","volume":"5","author":"K Gheybi","year":"2020","journal-title":"Int. J. Popul. Data Sci."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12885-019-6472-9","article-title":"Comorbidity prevalence among cancer patients: a population-based cohort study of four cancers.","volume":"20","author":"H Fowler","year":"2020","journal-title":"BMC Cancer."},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11101435","article-title":"Personalizing the prediction of colorectal cancer prognosis by incorporating comorbidities and functional status into prognostic nomograms.","volume":"11","author":"D Boakye","year":"2019","journal-title":"Cancers (Basel)."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"23-34","DOI":"10.6004\/jnccn.2017.7026","article-title":"Understanding comorbidity profiles and their effect on treatment and survival in patients with colorectal cancer.","volume":"16","author":"E Hahn","year":"2018","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"468-478.e7","DOI":"10.6004\/jnccn.2021.7030","article-title":"Comorbidities, rather than older age, are strongly associated with higher utilization of healthcare in colorectal cancer survivors.","volume":"20","author":"M Thong","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1596\/978-1-4648-0349-9","volume":"3","year":"2015","journal-title":"Cancer: disease control priorities."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"8232","DOI":"10.3390\/ijerph18158232","article-title":"Colorectal cancer in young and older adults in Uruguay: changes in recent incidence and mortality trends.","volume":"18","author":"C Musetti","year":"2021","journal-title":"Int. J. Environ. Res. Public Health."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1186\/s12885-020-06784-7","article-title":"Right- and left-sided colon cancers - specificity of molecular mechanisms in tumorigenesis and progression.","volume":"20","author":"K Mukund","year":"2020","journal-title":"BMC Cancer."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e671-e678","DOI":"10.1016\/j.clcc.2018.07.001","article-title":"Association of clinicopathologic and molecular markers on stage-specific survival of right versus left colon cancer.","volume":"17","author":"S Narayanan","year":"2018","journal-title":"Clin. Colorectal Cancer."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"648-655","DOI":"10.1007\/s11605-015-3026-6","article-title":"The worse prognosis of right-sided colon cancers compared with left-sided colon cancers: a systematic review and meta-analysis.","volume":"20","author":"M Yahagi","year":"2016","journal-title":"J. Gastrointest. Surg."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"264-273","DOI":"10.14740\/gr1062w","article-title":"Difference between left- and right-sided colorectal cancer: a focused review of the literature.","volume":"11","author":"B Baran","year":"2018","journal-title":"Gastroenterol. Res."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"157-163","DOI":"10.1159\/000443644","article-title":"Right-sided colon cancer as a distinct histopathological subtype with reduced prognosis.","volume":"33","author":"U Nitsche","year":"2016","journal-title":"Dig. Surg."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"89-95","DOI":"10.1093\/jnci\/djp436","article-title":"Protection from right- and left-sided colorectal neoplasms after colonoscopy: population-based study.","volume":"102","author":"H Brenner","year":"2010","journal-title":"J. Natl. Cancer Inst."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"361-373","DOI":"10.1002\/cam4.2673","article-title":"Metastatic patterns and survival outcomes in patients with stage IV colon cancer: A population-based analysis.","volume":"9","author":"J Wang","year":"2020","journal-title":"Cancer Med."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1221-1230","DOI":"10.5114\/aoms\/109170","article-title":"Correlation between KRAS, NRAS, and BRAF mutations and tumor localization in patients with primary and metastatic colorectal cancer.","volume":"18","author":"A Bo\u017cyk","year":"2022","journal-title":"Arch. Med. Sci."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"4697-4705","DOI":"10.1200\/JCO.2009.27.4860","article-title":"Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study.","volume":"28","author":"J Douillard","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"2011-2019","DOI":"10.1200\/JCO.2010.33.5091","article-title":"Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status.","volume":"29","author":"E Van Cutsem","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"6227","DOI":"10.3390\/cancers13246227","article-title":"T cell aging in patients with colorectal cancer: what do we know so far?","volume":"13","author":"O Thoma","year":"2021","journal-title":"Cancers (Basel)."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"7330-7349","DOI":"10.18632\/aging.202589","article-title":"Aging-related risk signature in colorectal cancer.","volume":"13","author":"T Yue","year":"2021","journal-title":"Aging (Albany NY)."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1186\/s40425-019-0656-3","article-title":"Immune cell concentrations among the primary tumor microenvironment in colorectal cancer patients predicted by clinicopathologic characteristics and blood indices.","volume":"7","author":"G Guo","year":"2019","journal-title":"J. Immunother. Cancer."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1949-1955","DOI":"10.1200\/JCO.2010.30.5037","article-title":"Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer.","volume":"29","author":"S Mahmoud","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.3390\/cancers15051457","article-title":"Immune microenvironment in sporadic early-onset versus average-onset colorectal cancer.","volume":"15","author":"F Andric","year":"2023","journal-title":"Cancers (Basel)."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"933-942","DOI":"10.1007\/s00262-021-03056-6","article-title":"Immune cell profiles in the tumor microenvironment of early-, intermediate-, and late-onset colorectal cancer.","volume":"71","author":"T Ugai","year":"2022","journal-title":"Cancer Immunol. Immunother."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"3817","DOI":"10.3390\/cancers14153817","article-title":"Retrospective cohort analysis of the effect of age on lymph node harvest, positivity, and ratio in colorectal cancer.","volume":"14","author":"S Lewis","year":"2022","journal-title":"Cancers (Basel)."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"2979","DOI":"10.3390\/cancers15112979","article-title":"Colorectal cancer in the young: research in early age colorectal cancer trends (REACCT) collaborative.","volume":"15","author":"A Zaborowski","year":"2023","journal-title":"Cancers (Basel)."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"808","DOI":"10.3390\/biology10080808","article-title":"Increased CD3+, CD8+, or FoxP3+ T lymphocyte infiltrations are associated with the pathogenesis of colorectal cancer but not with the overall survival of patients.","volume":"10","author":"A Barbosa","year":"2021","journal-title":"Biology (Basel)."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"9647-9659","DOI":"10.3390\/curroncol30110699","article-title":"Predictive value of CD3+\/CD8+ lymphocyte infiltration and PD-L1 expression in colorectal cancer.","volume":"30","author":"J Liu","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"514-523","DOI":"10.1038\/s41416-022-01822-6","article-title":"Prognostic significance of spatial and density analyses of T lymphocytes in colorectal cancer.","volume":"127","author":"H Elomaa","year":"2022","journal-title":"Br. J. Cancer."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"624-632","DOI":"10.1038\/s41416-020-0913-8","article-title":"Role of sex in the innate and adaptive immune environments of metastatic colorectal cancer.","volume":"123","author":"A Ray","year":"2020","journal-title":"Br. J. Cancer."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"2317-2326","DOI":"10.1158\/1055-9965.EPI-21-0508","article-title":"Density of CD3+ and CD8+ cells in the microenvironment of colorectal cancer according to prediagnostic physical activity.","volume":"30","author":"D Renman","year":"2021","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"986103","DOI":"10.3389\/fonc.2022.986103","article-title":"Analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer.","volume":"12","author":"A Geddes","year":"2022","journal-title":"Front. Oncol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"564648","DOI":"10.3389\/fcell.2020.564648","article-title":"Extracellular vesicles derived from colorectal cancer affect CD8 T cells: an analysis based on body mass index.","volume":"8","author":"N Abu","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"854-868","DOI":"10.1002\/ijc.30122","article-title":"Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltration.","volume":"139","author":"A Hanyuda","year":"2016","journal-title":"Int. J. Cancer."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"999-1006","DOI":"10.1007\/s11605-015-2759-6","article-title":"Immunoprofiling for prognostic assessment of colon cancer: a novel complement to ultra-aging.","volume":"19","author":"S Lavotshkin","year":"2015","journal-title":"J. Gastrointest. Surg."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"684-684","DOI":"10.1158\/1538-7445.AM2022-684","article-title":"Body mass index throughout adulthood and incidence of colorectal cancer subclassified by T cells, macrophages, and myeloid cell infiltrates in cancer tissues.","volume":"82","author":"T Ugai","year":"2022","journal-title":"Cancer Res."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.3390\/jcm12072451","article-title":"Why does obesity as an inflammatory condition predispose patients to colorectal cancer?","volume":"12","author":"A Rychter","year":"2023","journal-title":"J. Clin. Med."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"e20210042","DOI":"10.1084\/jem.20210042","article-title":"Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function.","volume":"219","author":"L Dyck","year":"2022","journal-title":"J. Exp. Med."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"141-151","DOI":"10.1038\/s41591-018-0221-5","article-title":"Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade.","volume":"25","author":"Z Wang","year":"2019","journal-title":"Nat. Med."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"206","DOI":"10.3390\/cancers15010206","article-title":"CD3+ and CD8+ T cell-based immune cell score and PD-(L)1 expression in pulmonary metastases of microsatellite stable colorectal cancer.","volume":"15","author":"T Karjula","year":"2022","journal-title":"Cancers (Basel)."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"100794","DOI":"10.1016\/j.eclinm.2021.100794","article-title":"Association between cardiovascular risk factors and colorectal cancer: a systematic review and meta-analysis of prospective cohort studies.","volume":"34","author":"C Zhang","year":"2021","journal-title":"eClinicalMedicine."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"887-894","DOI":"10.1007\/s00384-022-04129-3","article-title":"Increased standardized incidence ratio of cardiovascular diseases among patients with colorectal cancer patients.","volume":"37","author":"H Hsu","year":"2022","journal-title":"Int. J. Colorectal Dis."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.3389\/fimmu.2018.01578","article-title":"Immune landscape of colorectal cancer tumor microenvironment from different primary tumor locations.","volume":"9","author":"L Zhang","year":"2018","journal-title":"Front. Immunol."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/1479-5876-12-81","article-title":"CD8\/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival.","volume":"12","author":"V Koelzer","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"1781-1785","DOI":"10.15562\/bmj.v12i2.4520","article-title":"Identification of tumor-infiltrating lymphocyte CD8 in Indonesian colorectal cancer population: a cross-sectional study.","volume":"12","author":"E Irawan","year":"2023","journal-title":"Bali Med. J."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1654-1666","DOI":"10.1002\/ijc.30869","article-title":"The clinical impact of tumor-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite: a cohort study.","volume":"141","author":"J Berntsson","year":"2017","journal-title":"Int. J. Cancer."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"e37563","DOI":"10.7759\/cureus.37563","article-title":"Left-sided colon cancer and right-sided colon cancer: are they the same cancer or two different entities?","volume":"15","author":"M Bourakkadi Idrissi","year":"2023","journal-title":"Cureus."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"3063-3072","DOI":"10.1007\/s00432-021-03559-w","article-title":"Microsatellite instability (MSI-H) is associated with a high immunoscore, but not PD-L1 expression or increased survival in patients (pts.) with metastatic colorectal cancer (mCRC) treated with oxaliplatin (ox) and fluoropyrimidine (FP) with and without bevacizumab (bev): a pooled analysis of the AIO KRK 0207 and RO91 trials.","volume":"147","author":"S Noepel-Duennebacke","year":"2021","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1186\/s12967-018-1570-z","article-title":"Comparison of immunological characteristics between paired mismatch repair proficient and deficient colorectal cancer patients.","volume":"16","author":"S Liu","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"469-475","DOI":"10.1002\/bjs.4472","article-title":"Tumor-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic.","volume":"91","author":"S Phillips","year":"2004","journal-title":"Br. J. Surg."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"500-509","DOI":"10.1038\/bjc.2015.213","article-title":"Microsatellite unstable vs. stable colon carcinomas: analysis of tumor heterogeneity, inflammation, and angiogenesis.","volume":"113","author":"L De Smedt","year":"2015","journal-title":"Br. J. Cancer."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"698-711","DOI":"10.1016\/j.immuni.2016.02.025","article-title":"Integrative analyses of colorectal cancer show that immunoscore is a stronger predictor of patient survival than microsatellite instability.","volume":"44","author":"M Mlecnik","year":"2016","journal-title":"Immunity."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"116058","DOI":"10.1016\/j.biopha.2023.116058","article-title":"Unveiling the role of KRAS in the tumor immune microenvironment.","volume":"171","author":"M Xu","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"81778-81790","DOI":"10.18632\/oncotarget.13207","article-title":"Immunoscore encompassing CD3+ and CD8+ T cell densities in distant metastasis is a robust prognostic marker for advanced colorectal cancer.","volume":"7","author":"Y Kwak","year":"2016","journal-title":"Oncotarget."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"143-150","DOI":"10.1038\/s41416-023-02483-9","article-title":"Opposing roles by KRAS and BRAF mutation on immune cell infiltration in colorectal cancer - possible implications for immunotherapy.","volume":"130","author":"S Edin","year":"2024","journal-title":"Br. J. Cancer."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s12967-020-02638-9","article-title":"Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients.","volume":"19","author":"J Liu","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s11864-021-00870-z","article-title":"Beyond microsatellite instability: evolving strategies integrating immunotherapy for microsatellite stable colorectal cancer.","volume":"22","author":"F Pecci","year":"2021","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"e2203757","DOI":"10.1002\/advs.202203757","article-title":"Mutant KRAS drives immune evasion by sensitizing cytotoxic T-cells to activation-induced cell death in colorectal cancer.","volume":"10","author":"H Liu","year":"2023","journal-title":"Adv. Sci."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"e976052","DOI":"10.4161\/2162402X.2014.976052","article-title":"Immunogenomic stratification of colorectal cancer: implications for the development of targeted immunotherapy.","volume":"4","author":"N Lal","year":"2015","journal-title":"Onco Targets Ther."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.3390\/cancers14102383","article-title":"Immune profile of BRAF-mutated metastatic colorectal tumors with good prognosis after palliative chemotherapy.","volume":"14","author":"J Kim","year":"2022","journal-title":"Cancers (Basel)."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"1089-1093","DOI":"10.15562\/bmj.v12i1.4036","article-title":"Association between immunoscore with lymphovascular invasion and clinical staging in colorectal cancer.","volume":"12","author":"R Fachruddin","year":"2023","journal-title":"Clin. Bali Med. J."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"1104-1112","DOI":"10.1038\/modpathol.2016.95","article-title":"PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology, and cytotoxic tumor-infiltrating lymphocytes.","volume":"29","author":"M Rosenbaum","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"37588-37599","DOI":"10.18632\/oncotarget.5940","article-title":"OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer.","volume":"6","author":"B Weixler","year":"2015","journal-title":"Oncotarget."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"e1155","DOI":"10.1002\/cti2.1155","article-title":"CD8+ tumor-infiltrating lymphocytes within the primary tumor of patients with synchronous de novo metastatic colorectal carcinoma do not survive.","volume":"9","author":"R Millen","year":"2020","journal-title":"Clin. Transl. Immunol."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"e001294","DOI":"10.1136\/jitc-2020-001294","article-title":"Differential gene expression of tumor-infiltrating CD8+ T cells in advanced versus early stage cancer and identification of a gene signature with poor prognosis.","volume":"8","author":"R Saleh","year":"2020","journal-title":"J. Immunother. Cancer."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/s41598-020-80382-2","article-title":"The prognostic significance of CD8+ T-cells density in stage III colorectal cancer depends on SDF-1 expression.","volume":"11","author":"A Lalos","year":"2021","journal-title":"Sci. Rep."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"1012-1026.e3","DOI":"10.1016\/j.ccell.2018.11.003","article-title":"The link between multiple immune microenvironments in metastases and the survival of colorectal cancer patients.","volume":"34","author":"M Van den Eynde","year":"2018","journal-title":"Cancer Cell."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"327ra26","DOI":"10.1126\/scitranslmed.aad6352","article-title":"The tumor microenvironment and immune core are critical determinants of the dissemination to distant metastases.","volume":"8","author":"B Mlecnik","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"2654-2666","DOI":"10.1056\/NEJMoa051424","article-title":"Effector memory T cells, early metastasis, and survival in colorectal cancer.","volume":"353","author":"F Pag\u00e8s","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"21732","DOI":"10.1038\/s41598-022-26225-8","article-title":"Simultaneous analysis of tumor-infiltrating immune cell density, tumor budding status, and presence of lymphoid follicles in CRC tissue.","volume":"12","author":"A Markowski","year":"2022","journal-title":"Sci. Rep."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"2077","DOI":"10.1038\/s41598-023-29260-1","article-title":"Tumor-infiltrating T cells are a risk factor for lymph node metastasis in patients with submucosal colorectal cancer.","volume":"13","author":"M Kitakaze","year":"2023","journal-title":"Sci. Rep."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"1365-1378","DOI":"10.1016\/j.apsb.2021.03.027","article-title":"Role of CD8+ T lymphocyte cells: interplay with stromal cells in the tumor microenvironment.","volume":"11","author":"Q Xie","year":"2021","journal-title":"Acta Pharm. Sin. B."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"101962","DOI":"10.1016\/j.canep.2021.101962","article-title":"Impact of comorbidities at diagnosis on the 10-year colorectal cancer net survival: a population-based study.","volume":"73","author":"E Michalopoulou","year":"2021","journal-title":"Cancer Epidemiol."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"8580","DOI":"10.1038\/s41598-019-44969-8","article-title":"Effects of comorbidity on colorectal cancer mortality in an Australian cancer population.","volume":"9","author":"M Pule","year":"2019","journal-title":"Sci. Rep."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"5735","DOI":"10.3390\/cancers13225735","article-title":"Diabetes and cancer: risk, challenges, management and outcomes.","volume":"13","author":"R Shahid","year":"2021","journal-title":"Cancers (Basel)."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"868715","DOI":"10.3389\/fcell.2022.868715","article-title":"Chronic kidney disease and cancer: inter-relationships and mechanisms.","volume":"10","author":"M Hu","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"485","DOI":"10.3390\/cancers15020485","article-title":"Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management.","volume":"15","author":"S Pati","year":"2023 Jan 12","journal-title":"Cancers (Basel)."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"8742","DOI":"10.3390\/ijerph18168742","article-title":"Chronic Obstructive Pulmonary Disease Increases the Risk of Mortality among Patients with Colorectal Cancer: A Nationwide Population-Based Retrospective Cohort Study.","volume":"18","author":"W Cheng","year":"2021 Aug 19","journal-title":"Int. J. Environ. Res. Public Health."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"2005-2013","DOI":"10.1038\/bjc.2013.541","article-title":"Does comorbidity interact with colorectal cancer to increase mortality? A nationwide population-based cohort study.","volume":"109","author":"R Erichsen","year":"2013 Oct 1","journal-title":"Br. J. Cancer."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"355-362","DOI":"10.1097\/COC.0000000000000529","article-title":"Mental Health Disorders are More Common in Colorectal Cancer Survivors and Associated With Decreased Overall Survival.","volume":"42","author":"S Lloyd","year":"2019 Apr","journal-title":"Am. J. Clin. Oncol."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"196-207","DOI":"10.1016\/j.critrevonc.2009.11.004","article-title":"Cancer patients with cardiovascular disease have survival rates comparable to cancer patients within the age cohort of 10 years without cardiovascular morbidity.","volume":"76","author":"M Janssen-Heijnen","year":"2010","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"717-726","DOI":"10.1007\/s11523-023-00986-2","article-title":"Impact of cardiovascular comorbidities on the effectiveness and safety of bevacizumab in older patients with metastatic colorectal cancer.","volume":"18","author":"A Gouverneur","year":"2023","journal-title":"Target. Oncol."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"1758835918780140","DOI":"10.1177\/1758835918780140","article-title":"5-fluorouracil and cardiotoxicity: a review.","volume":"10","author":"J Sara","year":"2018 Jun 18","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"e006278","DOI":"10.1161\/JAHA.117.006278","article-title":"Cardiovascular Adverse Events in Patients With Cancer Treated With Bevacizumab: A Meta-Analysis of More Than 20 000 Patients.","volume":"6","author":"M Totzeck","year":"2017 Aug 10","journal-title":"J. Am. Heart Assoc."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"5218","DOI":"10.3390\/cancers13205218","article-title":"Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review.","volume":"13","author":"W Shalata","year":"2021 Oct 18","journal-title":"Cancers (Basel)."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"1080998","DOI":"10.3389\/fonc.2023.1080998","article-title":"Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis.","volume":"13","author":"F djana Lessomo","year":"2023 Mar 29","journal-title":"Front. Oncol."},{"key":"ref112","doi-asserted-by":"publisher","first-page":"847012","DOI":"10.3389\/fcvm.2022.847012","article-title":"Cardiotoxicity of Anticancer Drugs: Molecular Mechanisms and Strategies for Cardioprotection.","volume":"9","author":"M Morelli","year":"2022 Apr 15","journal-title":"Front. Cardiovasc. Med."},{"key":"ref113","doi-asserted-by":"publisher","first-page":"143-158","DOI":"10.1016\/j.jaccao.2024.02.001","article-title":"Cardiovascular Concerns, Cancer Treatment, and Biological and Chronological Aging in Cancer: JACC Family Series.","volume":"6","author":"D Ioffe","year":"2024 Apr 8","journal-title":"JACC CardioOncol."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"107796","DOI":"10.1016\/j.ypmed.2023.107796","article-title":"Cardiovascular-specific mortality and risk factors in colorectal Cancer patients: A cohort study based on registry data of over 500,000 individuals in the US.","volume":"179","author":"T Zhang","year":"2024 Feb","journal-title":"Prev. Med."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1186\/s12885-024-12568-0","article-title":"The association between systemic immune-inflammation index and cardiotoxicity related to 5-Fluorouracil in colorectal cancer.","volume":"24","author":"X Liu","year":"2024 Jun 29","journal-title":"BMC Cancer."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"139-145","DOI":"10.1016\/j.ijcard.2021.09.004","article-title":"Cancer and cardiovascular disease: The impact of cardiac rehabilitation and cardiorespiratory fitness on survival.","volume":"343","author":"T Williamson","year":"2021 Nov 15","journal-title":"Int. J. Cardiol."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"2108-2119","DOI":"10.21037\/tcr-20-3421","article-title":"Predictive and prognostic value of sex in localized colorectal cancer: SEER-based analysis.","volume":"10","author":"B Ma","year":"2021","journal-title":"Transl. Cancer Res."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"1942-1949","DOI":"10.1002\/ijc.30827","article-title":"Gender differences in colorectal cancer survival: a meta-analysis.","volume":"141","author":"Y Yang","year":"2017","journal-title":"Int. J. Cancer."},{"key":"ref120","doi-asserted-by":"publisher","first-page":"101204","DOI":"10.1016\/j.esmoop.2023.101204","article-title":"Sex and gender perspectives in colorectal cancer.","volume":"8","author":"I Baraibar","year":"2023","journal-title":"ESMO Open."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"105-118","DOI":"10.1016\/j.ejca.2020.08.024","article-title":"Immune scores in colorectal cancer: where are we?","volume":"140","author":"D Malka","year":"2020","journal-title":"Eur. J. Cancer."},{"key":"ref122","doi-asserted-by":"publisher","first-page":"13-17","DOI":"10.7454\/nrjs.v5i2.1081","article-title":"Survival Rate of Colorectal Cancer in Dr. Cipto Mangunkusumo Hospital.","volume":"5","author":"W Jeo","year":"2020","journal-title":"New Ropanasuri J. Surg."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"57-61","DOI":"10.1055\/s-0043-1761447","article-title":"Epidemiology of stage IV colorectal cancer: trends in the incidence, prevalence, age distribution, and impact on life span.","volume":"37","author":"M Ilyas","year":"2023","journal-title":"Clin. Colon Rectal Surg."},{"key":"ref124","doi-asserted-by":"publisher","first-page":"310","DOI":"10.21037\/atm-20-4932","article-title":"Primary tumor immune score fails to predict the prognosis of colorectal cancer liver metastases after hepatectomy in Chinese populations.","volume":"9","author":"H Lin","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"787208","DOI":"10.3389\/fgene.2021.787208","article-title":"Identification of potential biomarkers of prognostic value in colorectal cancer via tumor microenvironment data mining.","volume":"12","author":"L Li","year":"2022","journal-title":"Front. Genet."},{"key":"ref126","doi-asserted-by":"publisher","first-page":"1-5","DOI":"10.1155\/2024\/5578953","article-title":"Correlation between PD-L1 expression, clinicopathological factors, and metastasis risk in colorectal cancer patients.","volume":"2024","author":"A Zarbakhsh","year":"2024","journal-title":"Eur. J. Cancer Care."},{"key":"ref127","doi-asserted-by":"publisher","first-page":"135-151","DOI":"10.1111\/imm.13568","article-title":"Single-cell landscape and clinical outcomes of infiltrating B cells in colorectal cancer.","volume":"168","author":"J Xia","year":"2023 Jan","journal-title":"Immunology."},{"key":"ref128","doi-asserted-by":"publisher","first-page":"85","DOI":"10.3892\/ijo.2024.5673","article-title":"Myeloid-derived suppressor cells: Key immunosuppressive regulators and therapeutic targets in colorectal cancer (Review).","volume":"65","author":"W Zeng","year":"2024 Sep","journal-title":"Int. J. Oncol."},{"key":"ref129","doi-asserted-by":"publisher","first-page":"228","DOI":"10.3390\/cells12020228","article-title":"Using Single-Cell RNA Sequencing and MicroRNA Targeting Data to Improve Colorectal Cancer Survival Prediction.","volume":"12","author":"A Willems","year":"2023 Jan 5","journal-title":"Cells."},{"key":"ref130","doi-asserted-by":"publisher","first-page":"e33736","DOI":"10.7759\/cureus.33736","article-title":"Impact of KRAS mutations on survival outcomes of patients with metastatic colorectal cancer in Jordan.","volume":"15","author":"M Alkader","year":"2023","journal-title":"Cureus."},{"key":"ref131","doi-asserted-by":"publisher","first-page":"886-895","DOI":"10.21037\/jgo.2019.05.04","article-title":"Effect of KRAS mutational status on disease behavior and treatment outcome in patients with metastatic colorectal cancer: Intratumor heterogeneity and mutational status.","volume":"10","author":"A Rasmy","year":"2019","journal-title":"J. Gastrointest. Oncol."},{"key":"ref132","doi-asserted-by":"publisher","first-page":"3001-3008","DOI":"10.31557\/APJCP.2018.19.11.3001","article-title":"Prognostic value of the NRAS gene for survival of colorectal cancer patients: A systematic review and meta-analysis.","volume":"19","author":"Y Hu","year":"2018","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref133","doi-asserted-by":"publisher","first-page":"3513","DOI":"10.1200\/JCO.2018.36.15_suppl.3513","article-title":"Distinct impacts of KRAS, NRAS, and BRAF mutations on the survival of patients with metastatic colorectal cancer.","volume":"36","author":"Y Wang","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref134","doi-asserted-by":"publisher","first-page":"191-197","DOI":"10.1093\/oncolo\/oyab055","article-title":"BRAF mutations are associated with poor survival outcomes in advanced-stage mismatch repair-deficient\/microsatellite high colorectal cancer.","volume":"27","author":"E Tan","year":"2022","journal-title":"Oncologist."},{"key":"ref135","doi-asserted-by":"publisher","DOI":"10.17605\/OSF.IO\/M9E85","article-title":"The demographic profile of colorectal cancer patients in Indonesia: insights from a single center experience and exploration of immune response and survival outcomes.","author":"C Irawan","year":"2024, October 17"}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/13-1362\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/13-1362\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/13-1362\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:34:12Z","timestamp":1791894852000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/13-1362\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":132,"URL":"https:\/\/doi.org\/10.12688\/f1000research.155021.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.155021.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.198163.r476580","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.198163.r499220","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.198163.r476580","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.198163.r499220","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/13-1362\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.170136.r356601, Xishan Wang, Department of Colorectal Surgery, National Cancer Center\/National Clinical Research Center of Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 20 Jan 2025, version 1, 1 approved","URL":"https:\/\/f1000research.com\/articles\/13-1362\/v1#referee-response-356601","order":0,"name":"referee-response-356601","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Cosphiadi Irawan<\/b>; \n<i>Posted: 23 Jan 2025<\/i>; We appreciate the reviewer\u2019s insightful comment regarding the sample size. We acknowledge that the retrospective design and the limited sample size of 74 patients may affect the statistical power of subgroup analyses, particularly for rarer mutation profiles, specific treatment modalities, or comorbidities. These analyses may require larger sample sizes to draw more robust conclusions.  Our study focused on a single tertiary care center over a specific timeframe (2020-2022), which inherently limited the pool of eligible patients. The study included all eligible CRC patients treated during the study period, achieving near-complete case capture. The minimum sample size of 72 patients was determined based on an expected 3-year overall survival (OS) rate of 75%, with a 10% margin of error and a 95% confidence level, as described in the methods.  We agree that larger, multi-center studies are essential to enhance the statistical power for subgroup analyses and to validate our findings across diverse populations. This limitation has been acknowledged in the discussion section of our manuscript.  We also thank the reviewer for emphasizing the need to discuss the interaction between cardiovascular comorbidities, cancer treatments, and patient QoL. In response, we have expanded our discussion to address how cardiovascular conditions may limit treatment options, increase toxicity risks, and exacerbate side effects, collectively reducing QoL. We also highlight evidence linking cardiovascular comorbidities to functional limitations and higher symptom burdens.  We appreciate the reviewer\u2019s suggestion and have expanded the discussion to explore the mechanisms by which cardiovascular diseases influence CRC survival. Specifically, we now address how CVD limits treatment options, exacerbates systemic inflammation, and shares risk factors with CRC, which collectively contribute to poorer survival outcomes.   Thank you for your valuable feedback. We have addressed the concerns as follows:  Confounders and Comorbidities: The influence of comorbidities and other confounders on survival has been discussed in the manuscript. Multivariate Analysis: A multivariate analysis with adjusted hazard ratios for survival factors has been included in the study. Immune Score and Survival: We have explained the lack of significance in immune score and suggested future research exploring additional immunological markers and advanced profiling techniques to better understand the immune landscape\u2019s impact on survival. Immunotherapy Limitation: The absence of immunotherapy in the study population has been noted as a limitation in interpreting immune score-related survival data. Summary of Results: The relationship between patient demographics, tumor characteristics, and immune scores has been more clearly summarized. Geographical Comparison: We have added studies to highlight geographical differences in CRC, particularly in low-resource settings. Future Research Recommendations: A more explicit recommendation for future research exploring the interplay between immune response, tumor mutations, and survival has been added. Proofreading: A thorough proofreading has been conducted to correct typographical and grammatical errors. Figure Legend: The figure legend for the Kaplan-Meier curve in Figure 1 has been revised for clarity. The response to your suggestions regarding the justification for the study's sample size limitation, how cardiovascular comorbidities interact with cancer treatment regimens and impact patient quality of life, and the exploration of the mechanisms by which cardiovascular diseases influence CRC survival has been provided in the previous response.  We hope these revisions address your concerns. Thank you again for your thoughtful suggestions.","URL":"https:\/\/f1000research.com\/articles\/13-1362\/v2#referee-comment-13208","order":1,"name":"referee-comment-13208","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.198163.r476580, Smreti Vasudevan, Rajiv Gandhi Cancer Institute & Research Centre, Rohini, Delhi, 01 Jun 2026, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/13-1362\/v2#referee-response-476580","order":2,"name":"referee-response-476580","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.198163.r499220, Leonardo C\u00e1rcamo, Servicio de Cirug\u00eda, Hospital Base Valdivia, Valdivia, 10 Jul 2026, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/13-1362\/v2#referee-response-499220","order":3,"name":"referee-response-499220","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}