{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:19:52Z","timestamp":1792131592693,"version":"4.4.0"},"reference-count":50,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conicyt\u2013Fondap","award":["15130011"],"award-info":[{"award-number":["15130011"]}]},{"name":"Conicyt\u2013Fondap","award":["1523A0008"],"award-info":[{"award-number":["1523A0008"]}]},{"name":"Conicyt\u2013Fondap","award":["1231773"],"award-info":[{"award-number":["1231773"]}]},{"name":"Conicyt\u2013Fondap","award":["VIU20P0071"],"award-info":[{"award-number":["VIU20P0071"]}]},{"name":"ANID FONDAP apoyo","award":["15130011"],"award-info":[{"award-number":["15130011"]}]},{"name":"ANID FONDAP apoyo","award":["1523A0008"],"award-info":[{"award-number":["1523A0008"]}]},{"name":"ANID FONDAP apoyo","award":["1231773"],"award-info":[{"award-number":["1231773"]}]},{"name":"ANID FONDAP apoyo","award":["VIU20P0071"],"award-info":[{"award-number":["VIU20P0071"]}]},{"name":"Fondecyt","award":["15130011"],"award-info":[{"award-number":["15130011"]}]},{"name":"Fondecyt","award":["1523A0008"],"award-info":[{"award-number":["1523A0008"]}]},{"name":"Fondecyt","award":["1231773"],"award-info":[{"award-number":["1231773"]}]},{"name":"Fondecyt","award":["VIU20P0071"],"award-info":[{"award-number":["VIU20P0071"]}]},{"name":"FONDEF","award":["15130011"],"award-info":[{"award-number":["15130011"]}]},{"name":"FONDEF","award":["1523A0008"],"award-info":[{"award-number":["1523A0008"]}]},{"name":"FONDEF","award":["1231773"],"award-info":[{"award-number":["1231773"]}]},{"name":"FONDEF","award":["VIU20P0071"],"award-info":[{"award-number":["VIU20P0071"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and\/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia\/low-grade dysplasia [GIM\/LGD]), 21 with high-grade dysplasia\/early GC [HGD\/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I\/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies\/mL) was higher than that of the HD controls (139.00 copies\/mL) (p &lt; 0.0001). After dividing this cohort into training\u2013validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683\u20130.845) in the training group. This resulted in a cut-off value of 87.37 copies\/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM\/LGD, HGD\/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal\/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11\u20133.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53\u20139.93, p = 0.004) for the risk of developing GIM\/LGD and HGD\/eGC, respectively. The combined methylated RPRM cfDNA and PG-I\/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD\/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response.<\/jats:p>","DOI":"10.3390\/ijms26073333","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T04:33:43Z","timestamp":1743654823000},"page":"3333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Mar\u00eda Jos\u00e9","family":"Maturana","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Portugal 61, Santiago 8330023, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oslando","family":"Padilla","sequence":"additional","affiliation":[{"name":"School of Public Health, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8330023, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4342-8069","authenticated-orcid":false,"given":"Pablo M.","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Portugal 61, Santiago 8330023, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5133-1964","authenticated-orcid":false,"given":"Maria Alejandra","family":"Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Portugal 61, Santiago 8330023, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilda","family":"Olivares","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Portugal 61, Santiago 8330023, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3491-6898","authenticated-orcid":false,"given":"Alejandro","family":"Blanco","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica y Gen\u00f3mica, Instituto de Ciencias e Innovaci\u00f3n en Medicina (ICIM), Facultad de Medicina Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 7550000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2567-0521","authenticated-orcid":false,"given":"Ricardo","family":"Armisen","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica y Gen\u00f3mica, Instituto de Ciencias e Innovaci\u00f3n en Medicina (ICIM), Facultad de Medicina Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 7550000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Garrido","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Portugal 61, Santiago 8330023, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmundo","family":"Aravena","sequence":"additional","affiliation":[{"name":"Instituto Chileno Japones de Enfermedades Digestivas, Hospital Clinico San Borja Arriaran, Servicio Salud Metropolitano Central, Santiago, Chile and Fundaci\u00f3n Arturo L\u00f3pez P\u00e9rez, Santiago 8360160, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Barrientos","sequence":"additional","affiliation":[{"name":"Instituto Chileno Japones de Enfermedades Digestivas, Hospital Clinico San Borja Arriaran, Servicio Salud Metropolitano Central, Santiago, Chile and Fundaci\u00f3n Arturo L\u00f3pez P\u00e9rez, Santiago 8360160, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Calvo-Belmar","sequence":"additional","affiliation":[{"name":"Hospital Dr. Sotero del Rio, Servicio Salud Metropolitano Sur-Oriente, Santiago 8207257, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro H.","family":"Corval\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Faculty of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Portugal 61, Santiago 8330023, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101404","DOI":"10.1016\/j.eclinm.2022.101404","article-title":"The current and future incidence and mortality of gastric cancer in 185 countries, 2020\u22122040: A population-based modelling study","volume":"47","author":"Morgan","year":"2022","journal-title":"eClinicalMedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2126334","DOI":"10.1001\/jamanetworkopen.2021.26334","article-title":"Gastrointestinal Cancer Stage at Diagnosis Before and During the COVID-19 Pandemic in Japan","volume":"4","author":"Kuzuu","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1101\/gr.266221.120","article-title":"Mapping genome variation of SARS-CoV-2 worldwide highlights the impact of COVID-19 super-spreaders","volume":"30","author":"Bello","year":"2020","journal-title":"Genome Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1053\/j.gastro.2020.01.012","article-title":"Spotlight: Gastric Intestinal Metaplasia","volume":"158","author":"Shah","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/den.14063","article-title":"Endoscopic screening for gastric cancer in Japan: Current status and future perspectives","volume":"34","author":"Mabe","year":"2022","journal-title":"Dig. Endosc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1093\/jjco\/hyy077","article-title":"Update version of the Japanese Guidelines for Gastric Cancer Screening","volume":"48","author":"Hamashima","year":"2018","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.annonc.2020.02.011","article-title":"Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA","volume":"31","author":"Liu","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Locke, W.J., Guanzon, D., Ma, C., Liew, Y.J., Duesing, K.R., Fung, K.Y.C., and Ross, J.P. (2019). DNA Methylation Cancer Biomarkers: Translation to the Clinic. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.01150"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e159590","DOI":"10.1172\/jci.insight.159590","article-title":"Cell-free DNA topology depends on its subcellular and cellular origins in cancer","volume":"7","author":"Malkin","year":"2022","journal-title":"JCI Insight"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/bjc.2011.143","article-title":"Measurement of GSTP1 promoter methylation in body fluids may complement PSA screening: A meta-analysis","volume":"105","author":"Wu","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1136\/gutjnl-2012-304149","article-title":"Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer","volume":"63","author":"Church","year":"2014","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.molmed.2020.12.011","article-title":"Liquid Biopsy of Methylation Biomarkers in Cell-Free DNA","volume":"27","author":"Luo","year":"2021","journal-title":"Trends Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4","DOI":"10.5230\/jgc.2024.24.e5","article-title":"Liquid Biopsy: An Emerging Diagnostic, Prognostic, and Predictive Tool in Gastric Cancer","volume":"24","author":"Han","year":"2023","journal-title":"J. Gastric Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6264","DOI":"10.1158\/1078-0432.CCR-07-4522","article-title":"Reprimo as a potential biomarker for early detection in gastric cancer","volume":"14","author":"Bernal","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22627","DOI":"10.1074\/jbc.C000235200","article-title":"Reprimo, a new candidate mediator of the p53-mediated cell cycle arrest at the G2 phase","volume":"275","author":"Ohki","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e2413126122","DOI":"10.1073\/pnas.2413126122","article-title":"Extrinsic induction of apoptosis and tumor suppression via the p53-Reprimo-Hippo-YAP\/TAZ-p73 pathway","volume":"122","author":"Takikawa","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Saavedra, K., Valbuena, J., Olivares, W., Marchant, M.J., Rodriguez, A., Torres-Estay, V., Carrasco-Avino, G., Guzman, L., Aguayo, F., and Roa, J.C. (2015). Loss of Expression of Reprimo, a p53-induced Cell Cycle Arrest Gene, Correlates with Invasive Stage of Tumor Progression and p73 Expression in Gastric Cancer. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125834"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Amigo, J.D., Opazo, J.C., Garcia-Bloj, B.A., Alarcon, M.A., Owen, G.I., and Corvalan, A.H. (2018). The Reprimo Gene Family: A Novel Gene Lineage in Gastric Cancer with Tumor Suppressive Properties. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071862"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1002\/ijc.25274","article-title":"Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer","volume":"127","author":"Schneider","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Alarc\u00f3n, M.A., Olivares, W., C\u00f3rdova-Delgado, M., Mu\u00f1oz-Medel, M., de Mayo, T., Carrasco-Avi\u00f1o, G., Wichmann, I., Landeros, N., Amigo, J., and Norero, E. (2020). The Reprimo-Like Gene Is an Epigenetic-Mediated Tumor Suppressor and a Candidate Biomarker for the Non-Invasive Detection of Gastric Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249472"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Shigenobu, Y., Miyamori, D., Ikeda, K., Yoshida, S., Kikuchi, Y., Kanno, K., Kashima, S., and Ito, M. (2024). Assessing the Influence of the COVID-19 Pandemic on Gastric Cancer Mortality Risk. J. Clin. Med., 13.","DOI":"10.3390\/jcm13030715"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mondal, D., Shinde, S., Sinha, V., Dixit, V., Paul, S., Gupta, R.K., Thakur, S., Vishvakarma, N., and Shukla, D. (2024). Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1385238"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.3748\/wjg.v24.i26.2818","article-title":"Biomarkers of gastric cancer: Current topics and future perspective","volume":"24","author":"Matsuoka","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rendek, T., Pos, O., Duranova, T., Saade, R., Budi\u0161, J., Repiska, V., and Szeme\u0161, T. (2024). Current Challenges of Methylation-Based Liquid Biopsies in Cancer Diagnostics. Cancers, 16.","DOI":"10.3390\/cancers16112001"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3390\/curroncol31010033","article-title":"Plasma Cell-Free Tumor Methylome as a Biomarker in Solid Tumors: Biology and Applications","volume":"31","author":"Sacdalan","year":"2024","journal-title":"Curr. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"baac077","DOI":"10.1093\/database\/baac077","article-title":"LiqBioer: A manually curated database of cancer biomarkers in body fluid","volume":"2022","author":"Geng","year":"2022","journal-title":"Database"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108610","DOI":"10.18632\/oncotarget.21296","article-title":"The relationship between DNA methylation and Reprimo gene expression in gastric cancer cells","volume":"8","author":"Lai","year":"2017","journal-title":"Oncotarget"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/s10120-018-0803-4","article-title":"Novel epigenetic markers for gastric cancer risk stratification in individuals after Helicobacter pylori eradication","volume":"21","author":"Maeda","year":"2018","journal-title":"Gastric Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"673","DOI":"10.2147\/IJGM.S395951","article-title":"Value of Methylation Status of RPRM, SDC2, and TCF4 Genes in Plasma for Gastric Adenocarcinoma Screening","volume":"16","author":"Guo","year":"2023","journal-title":"Int. J. Gen. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1158\/2159-8290.CD-17-1009","article-title":"Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer","volume":"8","author":"Strickler","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.pmedr.2019.01.007","article-title":"Demographic, health, and attitudinal factors predictive of cancer screening decisions in older adults","volume":"13","author":"Schoenborn","year":"2019","journal-title":"Prev. Med. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41467-020-14310-3","article-title":"White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer","volume":"11","author":"Leal","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7098","DOI":"10.1158\/1078-0432.CCR-19-1704","article-title":"Circulating Tumor DNA Sequencing Analysis of Gastroesophageal Adenocarcinoma","volume":"25","author":"Maron","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Roma\u0144czyk, M., Osmola, M., Link, A., Druet, A., H\u00e9mont, C., Martin, J., Chapelle, N., and Matysiak-Budnik, T. (2024). Non-Invasive Markers for the Detection of Gastric Precancerous Conditions. Cancers, 16.","DOI":"10.3390\/cancers16122254"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2183\/pjab.87.405","article-title":"Gastric cancer screening by combined assay for serum anti-Helicobacter pylori IgG antibody and serum pepsinogen levels\u2014\u201cABC method\u201d","volume":"87","author":"Miki","year":"2011","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101731","DOI":"10.1016\/j.bpg.2021.101731","article-title":"Early detection of gastric cancer beyond endoscopy\u2014New methods","volume":"50","author":"Leja","year":"2021","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1053\/j.gastro.2011.05.040","article-title":"Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening","volume":"141","author":"Aikou","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.7150\/jca.95311","article-title":"Global progress and future prospects of early gastric cancer screening","volume":"15","author":"Huang","year":"2024","journal-title":"J. Cancer"},{"key":"ref_39","first-page":"45","article-title":"The clinical efficacy of CA 72-4 as serum marker for gastric cancer in comparison with CA19-9 and CEA","volume":"80","author":"Kodama","year":"1995","journal-title":"Int. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1136\/gutjnl-2020-322065","article-title":"Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population","volume":"70","author":"So","year":"2021","journal-title":"Gut"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"112187","DOI":"10.1016\/j.fct.2021.112187","article-title":"Fasting-mediated metabolic and toxicity reprogramming impacts circulating microRNA levels in humans","volume":"152","author":"Ravanidis","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Feng, G., Lin, Z., Ou, W.-E., Su, X., and Yan, Q. (2021). A Model-Based Meta-Analysis of Willingness to Participate in Cancer Screening. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18052580"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S419","DOI":"10.1016\/S0016-5085(11)61720-4","article-title":"Results of a Population-Based Gastric Cancer Screening Program Conducted in Chile 1996-2008","volume":"140","author":"Calvo","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1136\/gutjnl-2023-331059","article-title":"Comparison of OLGA and OLGIM as predictors of gastric cancer in a Latin American population: The ECHOS Study","volume":"73","author":"Latorre","year":"2024","journal-title":"Gut"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"57","DOI":"10.7748\/nr2005.07.13.1.57.c6000","article-title":"Creating user-friendly databases with Microsoft Access","volume":"13","author":"Schneider","year":"2005","journal-title":"Nurse Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/978-1-4939-7481-8_25","article-title":"MethyLight and Digital MethyLight","volume":"1708","author":"Campan","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Girgis, H.Z. (2022). MeShClust v3.0: High-quality clustering of DNA sequences using the mean shift algorithm and alignment-free identity scores. BMC Genom., 23.","DOI":"10.1186\/s12864-022-08619-0"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","article-title":"Jalview Version 2\u2014A multiple sequence alignment editor and analysis workbench","volume":"25","author":"Waterhouse","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3109\/00365521.2011.645501","article-title":"Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers","volume":"47","author":"Kuipers","year":"2012","journal-title":"Scand. J. Gastroenterol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3333\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:09:10Z","timestamp":1760029750000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":50,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26073333"],"URL":"https:\/\/doi.org\/10.3390\/ijms26073333","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,3]]}}}