{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:05:01Z","timestamp":1790006701246,"version":"4.0.1"},"reference-count":57,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n The phenotypic and morphologic heterogeneity of tumor vasculature in colorectal cancer (CRC) has been increasingly recognized; however, its clinical importance remains unclear.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To examine whether specific tumor vascular features are associated with CRC-specific mortality.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n The prospective cohort incident-tumor biobank method (PCIBM) was used to analyze data from the Nurses\u2019 Health Study and the Health Professionals Follow-up Study, in which 4476 incident CRC cases were documented and resected tumor tissue specimens were collected. Immunofluorescence staining was conducted from July 30 to August 14, 2024, and data analyses were performed between December 2024 and June 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Tumor vascular features were assessed by in situ multispectral immunofluorescence. The study used an in situ multispectral immunofluorescence assay targeting ACKR1 (atypical chemokine receptor 1), CD34 (cluster of differentiation 34), CD36 (cluster of differentiation 36), KDR (kinase insert domain receptor), LAMB1 (laminin subunit \u03b21), MADCAM1 (mucosal addressin cell adhesion molecule 1), and KRT (keratin) combined with machine learning to characterize tumor vasculature. The vessels were morphologically classified as micro, collapsed, patent, and irregular. Multivariable-adjusted Cox proportional hazards regression models were used to assess CRC mortality.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n CRC-specific mortality assessed using multivariable adjusted Cox proportional hazards regression models.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Tumor vessels were successfully analyzed in 837 patients with CRC (median [IQR] age at diagnosis, 69 [63-75] years; 466 [56%] female). During a median (IQR) follow-up of 11.8 (8.7-14.7) years for censored cases, there were 628 all-cause deaths, including 263 CRC-specific deaths. Multivariable-adjusted CRC-specific mortality hazard ratios were 0.39 (95% CI, 0.25-0.60;\n P<\/jats:italic>\n for trend &amp;lt;.001) for overall CD34\n +<\/jats:sup>\n vessel density in quartile 4 (vs quartile 1), 0.48 (95% CI, 0.31-0.74;\n P<\/jats:italic>\n for trend =\u2009.004) for micro CD34\n +<\/jats:sup>\n vessel proportion in quartile 4, 1.58 (95% CI, 1.07-2.32;\n P<\/jats:italic>\n for trend =\u2009.004) for CD34\n +<\/jats:sup>\n CD36\n +<\/jats:sup>\n vessel proportion highest category (vs lowest category), and 1.78 (95% CI, 1.22-2.61;\n P<\/jats:italic>\n for trend &amp;lt;.001) for CD34\n +<\/jats:sup>\n LAMB1\n +<\/jats:sup>\n vessel proportion highest category.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this PCIBM-based study of patients with CRC, higher overall CD34\n +<\/jats:sup>\n vessel density was associated with better prognosis, whereas higher CD34\n +<\/jats:sup>\n CD36\n +<\/jats:sup>\n and CD34\n +<\/jats:sup>\n LAMB1\n +<\/jats:sup>\n vessel proportions were associated with worse prognosis. These findings suggest that tumor vasculature may have a role as a prognostic biomarker and potential therapeutic target.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.34883","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:30:44Z","timestamp":1790004644000},"page":"e2634883","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Vascular Features and Colorectal Cancer\u2013Specific Mortality"],"prefix":"10.1001","volume":"9","author":[{"given":"Kosuke","family":"Matsuda","sequence":"first","affiliation":[{"name":"Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Miyahara","sequence":"additional","affiliation":[{"name":"Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Ugai","sequence":"additional","affiliation":[{"name":"Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Nakazawa","sequence":"additional","affiliation":[{"name":"Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jules","family":"Cazaubiel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts"},{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayu","family":"Higashioka","sequence":"additional","affiliation":[{"name":"Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kondo","sequence":"additional","affiliation":[{"name":"Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxue","family":"Zhong","sequence":"additional","affiliation":[{"name":"Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"},{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts"},{"name":"Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston"},{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Meyerhardt","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marios","family":"Giannakis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts"},{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Nowak","sequence":"additional","affiliation":[{"name":"Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha P.","family":"V\u00e4yrynen","sequence":"additional","affiliation":[{"name":"Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomotaka","family":"Ugai","sequence":"additional","affiliation":[{"name":"Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Ogino","sequence":"additional","affiliation":[{"name":"Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"},{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts"},{"name":"Division of Nutrition, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"issue":"2","key":"zoi260944r1","article-title":"Colorectal cancer statistics, 2026.","volume":"76","author":"Siegel","year":"2026","journal-title":"CA Cancer J Clin"},{"issue":"12","key":"zoi260944r2","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1038\/s41568-025-00872-1","article-title":"The immune microenvironment of colorectal cancer.","volume":"25","author":"Kennel","year":"2025","journal-title":"Nat Rev Cancer"},{"issue":"4","key":"zoi260944r3","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70313","article-title":"Angiogenesis and targeted therapy in the tumour microenvironment: from basic to clinical practice.","volume":"15","author":"Yang","year":"2025","journal-title":"Clin Transl Med"},{"issue":"8024","key":"zoi260944r4","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/s41586-024-07698-1","article-title":"Tumour vasculature at single-cell resolution.","volume":"632","author":"Pan","year":"2024","journal-title":"Nature"},{"issue":"2","key":"zoi260944r5","doi-asserted-by":"publisher","first-page":"753","DOI":"10.21873\/invivo.12762","article-title":"A prognostic model of colon cancer based on the microenvironment component score via single cell sequencing.","volume":"36","author":"Liu","year":"2022","journal-title":"In Vivo"},{"issue":"3","key":"zoi260944r6","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.ccell.2023.02.002","article-title":"High endothelial venules in cancer: regulation, function, and therapeutic implication.","volume":"41","author":"Vella","year":"2023","journal-title":"Cancer Cell"},{"issue":"10","key":"zoi260944r7","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1038\/s41568-024-00736-0","article-title":"Targeting the tumour vasculature: from vessel destruction to promotion.","volume":"24","author":"Guelfi","year":"2024","journal-title":"Nat Rev Cancer"},{"issue":"9","key":"zoi260944r8","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/s41422-020-0355-0","article-title":"A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling.","volume":"30","author":"Qian","year":"2020","journal-title":"Cell Res"},{"issue":"8","key":"zoi260944r9","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/s41568-023-00591-5","article-title":"Understanding tumour endothelial cell heterogeneity and function from single-cell omics.","volume":"23","author":"Zeng","year":"2023","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"zoi260944r10","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.ccell.2019.12.001","article-title":"An integrated gene expression landscape profiling approach to identify lung tumor endothelial cell heterogeneity and angiogenic candidates.","volume":"37","author":"Goveia","year":"2020","journal-title":"Cancer Cell"},{"issue":"1","key":"zoi260944r11","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s00018-024-05411-z","article-title":"Endothelial cell heterogeneity in colorectal cancer: tip cells drive angiogenesis.","volume":"81","author":"Xie","year":"2024","journal-title":"Cell Mol Life Sci"},{"issue":"18","key":"zoi260944r12","doi-asserted-by":"publisher","first-page":"4734","DOI":"10.1016\/j.cell.2021.08.003","article-title":"Spatially organized multicellular immune hubs in human colorectal cancer.","volume":"184","author":"Pelka","year":"2021","journal-title":"Cell"},{"issue":"9","key":"zoi260944r13","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/s41577-022-00694-4","article-title":"Immunomodulation by endothelial cells - partnering up with the immune system?","volume":"22","author":"Amersfoort","year":"2022","journal-title":"Nat Rev Immunol"},{"issue":"15","key":"zoi260944r14","doi-asserted-by":"publisher","first-page":"5223","DOI":"10.7150\/thno.84947","article-title":"Visualizing vasculature and its response to therapy in the tumor microenvironment.","volume":"13","author":"Lin","year":"2023","journal-title":"Theranostics"},{"issue":"1","key":"zoi260944r15","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s40364-025-00883-y","article-title":"Tumor-associated endothelial cells in tumor immune escape and immunotherapy: multifaceted roles and treatment approaches.","volume":"14","author":"Zheng","year":"2025","journal-title":"Biomark Res"},{"issue":"2","key":"zoi260944r16","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1159\/000087840","article-title":"Absence of smooth muscle actin-positive pericyte coverage of tumor vessels correlates with hematogenous metastasis and prognosis of colorectal cancer patients.","volume":"69","author":"Yonenaga","year":"2005","journal-title":"Oncology"},{"issue":"22","key":"zoi260944r17","doi-asserted-by":"publisher","first-page":"19163","DOI":"10.18632\/oncotarget.4383","article-title":"Continuous representation of tumor microvessel density and detection of angiogenic hotspots in histological whole-slide images.","volume":"6","author":"Kather","year":"2015","journal-title":"Oncotarget"},{"issue":"3","key":"zoi260944r18","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1002\/path.6238","article-title":"Image-based multiplex immune profiling of cancer tissues: translational implications: a report of the International Immuno-oncology Biomarker Working Group on Breast Cancer.","volume":"262","author":"Jahangir","year":"2024","journal-title":"J Pathol"},{"key":"zoi260944r19","doi-asserted-by":"publisher","DOI":"10.1016\/j.lana.2025.101290","article-title":"Unique role of the prospective cohort incident-tumor biobank method in etiological research.","volume":"53","author":"Ogino","year":"2026","journal-title":"Lancet Reg Health Am"},{"key":"zoi260944r20","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/s44360-026-00122-0","article-title":"Environmental and lifestyle drivers of early-onset cancer.","volume":"1","author":"Hamada","year":"2026","journal-title":"Nat Health"},{"issue":"12","key":"zoi260944r21","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1056\/NEJMoa1301969","article-title":"Long-term colorectal-cancer incidence and mortality after lower endoscopy.","volume":"369","author":"Nishihara","year":"2013","journal-title":"N Engl J Med"},{"issue":"17","key":"zoi260944r22","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1056\/NEJMoa1207756","article-title":"Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival.","volume":"367","author":"Liao","year":"2012","journal-title":"N Engl J Med"},{"issue":"9","key":"zoi260944r23","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1038\/s41416-020-0780-3","article-title":"An integrated analysis of lymphocytic reaction, tumour molecular characteristics and patient survival in colorectal cancer.","volume":"122","author":"Haruki","year":"2020","journal-title":"Br J Cancer"},{"issue":"21","key":"zoi260944r24","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1056\/NEJMoa067208","article-title":"Aspirin and the risk of colorectal cancer in relation to the expression of COX-2.","volume":"356","author":"Chan","year":"2007","journal-title":"N Engl J Med"},{"issue":"6","key":"zoi260944r25","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1136\/gutjnl-2011-300865","article-title":"Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum.","volume":"61","author":"Yamauchi","year":"2012","journal-title":"Gut"},{"issue":"6","key":"zoi260944r26","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1136\/gutjnl-2012-302014","article-title":"Colorectal cancer: a tale of two sides or a continuum?","volume":"61","author":"Yamauchi","year":"2012","journal-title":"Gut"},{"issue":"4","key":"zoi260944r27","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.celrep.2016.03.075","article-title":"Genomic correlates of immune-cell infiltrates in colorectal carcinoma.","volume":"15","author":"Giannakis","year":"2016","journal-title":"Cell Rep"},{"issue":"3","key":"zoi260944r28","doi-asserted-by":"publisher","first-page":"305","DOI":"10.2353\/jmoldx.2007.060170","article-title":"Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer by a large population-based sample.","volume":"9","author":"Ogino","year":"2007","journal-title":"J Mol Diagn"},{"issue":"12","key":"zoi260944r29","doi-asserted-by":"publisher","first-page":"2767","DOI":"10.1002\/ijc.23470","article-title":"LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer.","volume":"122","author":"Ogino","year":"2008","journal-title":"Int J Cancer"},{"key":"zoi260944r30","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/1476-4598-13-135","article-title":"Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review.","volume":"13","author":"Imamura","year":"2014","journal-title":"Mol Cancer"},{"issue":"2","key":"zoi260944r31","doi-asserted-by":"publisher","first-page":"177","DOI":"10.2353\/jmoldx.2010.090106","article-title":"Precision of pyrosequencing assay to measure LINE-1 methylation in colon cancer, normal colonic mucosa, and peripheral blood cells.","volume":"12","author":"Irahara","year":"2010","journal-title":"J Mol Diagn"},{"issue":"10","key":"zoi260944r32","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1038\/s41416-026-03373-6","article-title":"Tumor vessel phenotype in colorectal cancer microenvironment according to age at diagnosis.","volume":"134","author":"Matsuda","year":"2026","journal-title":"Br J Cancer"},{"issue":"3","key":"zoi260944r33","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1073\/pnas.2025207118","article-title":"Opinion: standardizing gene product nomenclature-a call to action.","volume":"118","author":"Fujiyoshi","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"zoi260944r34","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s10654-017-0346-8","article-title":"Utility of inverse probability weighting in molecular pathological epidemiology.","volume":"33","author":"Liu","year":"2018","journal-title":"Eur J Epidemiol"},{"issue":"7","key":"zoi260944r35","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1038\/bjc.2012.369","article-title":"Vascular density analysis in colorectal cancer patients treated with vatalanib (PTK787\/ZK222584) in the randomised CONFIRM trials.","volume":"107","author":"Giatromanolaki","year":"2012","journal-title":"Br J Cancer"},{"issue":"3","key":"zoi260944r36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091811","article-title":"The clinical implication of cancer-associated microvasculature and fibroblast in advanced colorectal cancer patients with synchronous or metachronous metastases.","volume":"9","author":"Kwak","year":"2014","journal-title":"PLoS One"},{"issue":"4","key":"zoi260944r37","doi-asserted-by":"publisher","first-page":"839","DOI":"10.3892\/or.6.4.839","article-title":"Prognostic relevance of microvessel density in colorectal tumours.","volume":"6","author":"Abdalla","year":"1999","journal-title":"Oncol Rep"},{"issue":"5","key":"zoi260944r38","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1046\/j.1365-2559.2003.01610.x","article-title":"Microvessel densities and microvascular architecture in colorectal carcinomas and their liver metastases: significant correlation of high microvessel densities with better survival.","volume":"42","author":"Prall","year":"2003","journal-title":"Histopathology"},{"issue":"4","key":"zoi260944r39","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s41416-019-0519-1","article-title":"Stroma-normalised vessel density predicts benefit from adjuvant fluorouracil-based chemotherapy in patients with stage II\/III colon cancer.","volume":"121","author":"Mezheyeuski","year":"2019","journal-title":"Br J Cancer"},{"issue":"12","key":"zoi260944r40","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1038\/sj.bjc.6603176","article-title":"Microvessel density and VEGF expression are prognostic factors in colorectal cancer: meta-analysis of the literature.","volume":"94","author":"Des Guetz","year":"2006","journal-title":"Br J Cancer"},{"issue":"1","key":"zoi260944r41","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s12876-019-1063-4","article-title":"Prognostic value of microvessel density in stage II and III colon cancer patients: a retrospective cohort study.","volume":"19","author":"den Uil","year":"2019","journal-title":"BMC Gastroenterol"},{"issue":"3","key":"zoi260944r42","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1152\/physrev.00038.2010","article-title":"Normalization of the vasculature for treatment of cancer and other diseases.","volume":"91","author":"Goel","year":"2011","journal-title":"Physiol Rev"},{"key":"zoi260944r43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1291530","article-title":"Targeting vascular normalization: a promising strategy to improve immune-vascular crosstalk in cancer immunotherapy.","volume":"14","author":"Qian","year":"2023","journal-title":"Front Immunol"},{"issue":"10","key":"zoi260944r44","doi-asserted-by":"publisher","first-page":"7680","DOI":"10.3390\/curroncol29100607","article-title":"Single-cell transcriptomics of endothelial cells in upper and lower human esophageal squamous cell carcinoma.","volume":"29","author":"Sha","year":"2022","journal-title":"Curr Oncol"},{"issue":"19","key":"zoi260944r45","doi-asserted-by":"publisher","first-page":"23","DOI":"10.3390\/ijms231911052","article-title":"Metabolic reprogramming in tumor endothelial cells.","volume":"23","author":"Garc\u00eda-Caballero","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"3","key":"zoi260944r46","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/s12276-024-01180-8","article-title":"Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer.","volume":"56","author":"Bae","year":"2024","journal-title":"Exp Mol Med"},{"issue":"1","key":"zoi260944r47","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1080\/07853890.2022.2153911","article-title":"High endothelial venules proportion in tertiary lymphoid structure is a prognostic marker and correlated with anti-tumor immune microenvironment in colorectal cancer.","volume":"55","author":"Zhan","year":"2023","journal-title":"Ann Med"},{"issue":"8","key":"zoi260944r48","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1158\/1078-0432.CCR-13-2590","article-title":"Occurrence of tertiary lymphoid tissue is associated with T-cell infiltration and predicts better prognosis in early-stage colorectal cancers.","volume":"20","author":"Di Caro","year":"2014","journal-title":"Clin Cancer Res"},{"issue":"5","key":"zoi260944r49","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/s41416-019-0514-6","article-title":"High endothelial venules are associated with microsatellite instability, hereditary background and immune evasion in colorectal cancer.","volume":"121","author":"Pfuderer","year":"2019","journal-title":"Br J Cancer"},{"issue":"10","key":"zoi260944r50","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/s41571-022-00672-8","article-title":"Is early-onset cancer an emerging global epidemic? current evidence and future implications.","volume":"19","author":"Ugai","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"issue":"2","key":"zoi260944r51","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1093\/jnci\/djaf304","article-title":"Trends and projected burden of early-onset gastrointestinal malignancies in the United States: a population-based analysis (2001-2021).","volume":"118","author":"Yasinzai","year":"2026","journal-title":"J Natl Cancer Inst"},{"issue":"12","key":"zoi260944r52","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.7326\/ANNALS-24-02718","article-title":"Trends in cancer incidence in younger and older adults: an international comparative analysis.","volume":"178","author":"Berrington de Gonzalez","year":"2025","journal-title":"Ann Intern Med"},{"key":"zoi260944r53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nutres.2026.01.007","article-title":"Dark side of nocturnal eating: unraveling the emerging axis between meal timing, gut microbiota, and early-onset cancer risk.","volume":"148","author":"Khan","year":"2026","journal-title":"Nutr Res"},{"key":"zoi260944r54","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2026.116869","article-title":"Association between lifestyle and risk of early-onset cancer: evidence from the European Prospective Investigation into Cancer and Nutrition and the UK Biobank.","volume":"243","author":"Sala","year":"2026","journal-title":"Eur J Cancer"},{"issue":"12","key":"zoi260944r55","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/j.annonc.2024.08.2336","article-title":"The global epidemic of early-onset cancer: nature, nurture, or both?","volume":"35","author":"Ogino","year":"2024","journal-title":"Ann Oncol"},{"issue":"12","key":"zoi260944r56","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1007\/s10654-025-01322-w","article-title":"The early-onset cancer epidemics: evidence synthesis using the prospective cohort incident-tumor biobank method.","volume":"40","author":"Ogino","year":"2025","journal-title":"Eur J Epidemiol"},{"issue":"4","key":"zoi260944r57","doi-asserted-by":"publisher","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity analysis in observational research: introducing the E-value.","volume":"167","author":"VanderWeele","year":"2017","journal-title":"Ann Intern Med"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2854269\/matsuda_2026_oi_260944_1789154678.17536.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:30:45Z","timestamp":1790004645000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2854269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":57,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.34883","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}