{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:51:47Z","timestamp":1792086707855,"version":"4.4.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangxi Key R&D Program","award":["20222069"],"award-info":[{"award-number":["20222069"]}]},{"name":"Key R&D Program of Qingxiu District, Nanning","award":["2022010"],"award-info":[{"award-number":["2022010"]}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Screening for gastric cancer (GC) is critical for improving patient survival, yet current clinical methods suffer from invasiveness and limited sensitivity. The aim of this study is to develop a machine learning model for the non-invasive diagnosis of GC using the whole-genome methylation profile of circulating free DNA (cfDNA) in plasma. Plasma cfDNA from 61 patients with GC and 29 healthy controls. First, whole\u2011genome bisulfite sequencing (WGBS) was performed on 29 paired GC and adjacent normal tissues to identify differentially methylated regions (DMRs). These tissue DMRs were then mapped to plasma cfDNA methylation data, yielding 32 stable DMRs that changed consistently in both tissues and plasma. Using LASSO and Random Forest (RF) algorithms, eight core diagnostic markers were selected. Four machine learning algorithms (Support Vector Machine, RF, K-Nearest Neighbor, Na\u00efve Bayes) were used to build diagnostic models. WGBS revealed global hypomethylation and CpG island hypermethylation in GC, consistent with plasma cfDNA methylation patterns. The RF model built on the eight cfDNA methylation markers (annotated to genes including ATP8A2) performed best, achieving AUC values of 0.978 and 0.938 in the training and independent test sets, respectively, with an accuracy of 88.46%, sensitivity of 94.44%, and specificity of 75.00%. After adjusting for age, the model achieved an AUC of 0.924 on the test set, still demonstrating high discriminatory performance. Functional analysis implicated these markers in pathways such as phagocytosis and axon guidance, and showed significant correlation with immune cell infiltration. Notably, these core DMRs are not covered by the probes on the methylation arrays (450K and EPIC v2), highlighting the advantage of WGBS for novel biomarker discovery. In conclusion, tissue-plasma concordance analysis identified a panel of plasma cfDNA methylation biomarkers with strong diagnostic potential. The resulting RF model provides a promising non-invasive strategy for GC screening.<\/jats:p>","DOI":"10.1371\/journal.pgen.1012322","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:35:01Z","timestamp":1792085701000},"page":"e1012322","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genome-Wide DNA methylation profiling of tissue-plasma pairs identifies Novel cfDNA biomarkers for the diagnosis of gastric cancer"],"prefix":"10.1371","volume":"22","author":[{"given":"Hailing","family":"Ou","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Guangxi University of Chinese Medicine","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0589-1645","authenticated-orcid":true,"given":"Jinli","family":"Miao","sequence":"additional","affiliation":[{"name":"The Yangtze River Delta Biological Medicine Research and Development Center of Zhejiang Province, Yangtze Delta Region Institution of Tsinghua University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusheng","family":"Ling","sequence":"additional","affiliation":[{"name":"Guangxi Medical University Cancer Hospital","place":["Nanning, Guangxi, China"],"department":["Department of Gastrointestinal Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[{"name":"Guangxi Medical University Cancer Hospital","place":["Nanning, Guangxi, China"],"department":["Department of Gastrointestinal Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingan","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangxi Medical University Cancer Hospital","place":["Nanning, Guangxi, China"],"department":["Department of Gastrointestinal Surgery"]},{"name":"State Key Laboratory of Targeting Oncology, Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Ye","sequence":"additional","affiliation":[{"name":"Guangxi Medical University Cancer Hospital","place":["Nanning, Guangxi, China"],"department":["Department of Gastrointestinal Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunbo","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Yangtze River Delta Biological Medicine Research and Development Center of Zhejiang Province, Yangtze Delta Region Institution of Tsinghua University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwei","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangxi Medical University Cancer Hospital","place":["Nanning, Guangxi, China"],"department":["Department of Gastrointestinal Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0669-6806","authenticated-orcid":true,"given":"Yuzhou","family":"Qin","sequence":"additional","affiliation":[{"name":"Guangxi Medical University Cancer Hospital","place":["Nanning, Guangxi, China"],"department":["Department of Gastrointestinal Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"issue":"3","key":"pgen.1012322.ref001","first-page":"209","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"},{"issue":"16","key":"pgen.1012322.ref002","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.3748\/wjg.v29.i16.2452","article-title":"Updates on global epidemiology, risk and prognostic factors of gastric cancer","volume":"29","author":"W-J Yang","year":"2023","journal-title":"World J Gastroenterol"},{"issue":"1","key":"pgen.1012322.ref003","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13045-023-01451-3","article-title":"Gastric cancer treatment: recent progress and future perspectives","volume":"16","author":"W-L Guan","year":"2023","journal-title":"J Hematol Oncol"},{"key":"pgen.1012322.ref004","doi-asserted-by":"crossref","first-page":"1630628","DOI":"10.3389\/fonc.2025.1630628","article-title":"Artificial intelligence in advanced gastric cancer: a comprehensive review of applications in precision oncology","volume":"15","author":"M Fu","year":"2025","journal-title":"Front Oncol"},{"issue":"5","key":"pgen.1012322.ref005","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3390\/jpm15050166","article-title":"Beyond Biomarkers: Machine Learning-Driven Multiomics for Personalized Medicine in Gastric Cancer","volume":"15","author":"D Ma","year":"2025","journal-title":"J Pers Med"},{"issue":"1","key":"pgen.1012322.ref006","doi-asserted-by":"crossref","first-page":"2461679","DOI":"10.1080\/07853890.2025.2461679","article-title":"Artificial intelligence-assisted diagnosis of early gastric cancer: present practice and future prospects","volume":"57","author":"C Lei","year":"2025","journal-title":"Ann Med"},{"issue":"10","key":"pgen.1012322.ref007","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":"Y Huang","year":"2024","journal-title":"J Cancer"},{"issue":"17","key":"pgen.1012322.ref008","doi-asserted-by":"crossref","first-page":"13219","DOI":"10.3390\/ijms241713219","article-title":"Using cfDNA and ctDNA as Oncologic Markers: A Path to Clinical Validation","volume":"24","author":"J Dao","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"11","key":"pgen.1012322.ref009","doi-asserted-by":"crossref","first-page":"101281","DOI":"10.1016\/j.xcrm.2023.101281","article-title":"Cell-free multi-omics analysis reveals potential biomarkers in gastrointestinal cancer patients\u2019 blood","volume":"4","author":"Y Tao","year":"2023","journal-title":"Cell Rep Med"},{"issue":"1","key":"pgen.1012322.ref010","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s40478-022-01371-2","article-title":"DNA methylation as a diagnostic tool","volume":"10","author":"K Galbraith","year":"2022","journal-title":"Acta Neuropathol Commun"},{"issue":"2","key":"pgen.1012322.ref011","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.trecan.2019.12.006","article-title":"Diagnostic Power of DNA Methylation Classifiers for Early Detection of Cancer","volume":"6","author":"D Roy","year":"2020","journal-title":"Trends Cancer"},{"issue":"1","key":"pgen.1012322.ref012","doi-asserted-by":"crossref","first-page":"2539995","DOI":"10.1080\/15592294.2025.2539995","article-title":"Advancements in DNA methylation technologies and their application in cancer diagnosis","volume":"20","author":"Y Yang","year":"2025","journal-title":"Epigenetics"},{"issue":"10149","key":"pgen.1012322.ref013","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/S0140-6736(18)31268-6","article-title":"Principles of DNA methylation and their implications for biology and medicine","volume":"392","author":"Y Dor","year":"2018","journal-title":"Lancet"},{"issue":"5","key":"pgen.1012322.ref014","article-title":"Beyond the base pairs: comparative genome-wide DNA methylation profiling across sequencing technologies","volume":"25","author":"X Liu","year":"2024","journal-title":"Brief Bioinform"},{"issue":"3","key":"pgen.1012322.ref015","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/bjc.2013.351","article-title":"Epigenetic alteration: new insights moving from tissue to plasma - the example of PCDH10 promoter methylation in colorectal cancer","volume":"109","author":"E Danese","year":"2013","journal-title":"Br J Cancer"},{"key":"pgen.1012322.ref016","doi-asserted-by":"crossref","first-page":"115540","DOI":"10.1016\/j.biopha.2023.115540","article-title":"Efferocytosis: An accomplice of cancer immune escape","volume":"167","author":"H Qiu","year":"2023","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"pgen.1012322.ref017","doi-asserted-by":"crossref","first-page":"166583","DOI":"10.1016\/j.bbadis.2022.166583","article-title":"Blood-based DNA methylation signatures in cancer: A systematic review","volume":"1869","author":"Y Li","year":"2023","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"22","key":"pgen.1012322.ref018","doi-asserted-by":"crossref","first-page":"5724","DOI":"10.1158\/1078-0432.CCR-17-3364","article-title":"Detection of gastric cancer with novel methylated DNA markers: discovery, tissue validation, and pilot testing in plasma","volume":"24","author":"BW Anderson","year":"2018","journal-title":"Clin Cancer Res"},{"issue":"22","key":"pgen.1012322.ref019","doi-asserted-by":"crossref","first-page":"6135","DOI":"10.1158\/1078-0432.CCR-21-1982","article-title":"EpiPanGI Dx: A Cell-free DNA Methylation Fingerprint for the Early Detection of Gastrointestinal Cancers","volume":"27","author":"R Kandimalla","year":"2021","journal-title":"Clin Cancer Res"},{"issue":"10","key":"pgen.1012322.ref020","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1111\/cas.16284","article-title":"Plasma cell-free DNA methylome-based liquid biopsy for accurate gastric cancer detection","volume":"115","author":"J Qi","year":"2024","journal-title":"Cancer Sci"},{"issue":"9","key":"pgen.1012322.ref021","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-006013","article-title":"Cell-free DNA approaches for cancer early detection and interception","volume":"11","author":"JE Medina","year":"2023","journal-title":"J Immunother Cancer"},{"issue":"3","key":"pgen.1012322.ref022","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/s41551-021-00837-3","article-title":"Limitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics","volume":"6","author":"P Song","year":"2022","journal-title":"Nat Biomed Eng"},{"key":"pgen.1012322.ref023","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ymeth.2020.10.002","article-title":"DNA methylation methods: Global DNA methylation and methylomic analyses","volume":"187","author":"S Li","year":"2021","journal-title":"Methods"},{"issue":"8","key":"pgen.1012322.ref024","doi-asserted-by":"crossref","first-page":"4247","DOI":"10.3390\/ijms22084247","article-title":"DNA Methylation in Solid Tumors: Functions and Methods of Detection","volume":"22","author":"A Martisova","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"11","key":"pgen.1012322.ref025","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.3390\/cancers11111741","article-title":"Cell-Free DNA Methylation Profiling Analysis-Technologies and Bioinformatics","volume":"11","author":"J Huang","year":"2019","journal-title":"Cancers (Basel)"},{"issue":"1","key":"pgen.1012322.ref026","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s13148-025-01967-0","article-title":"DNA methylation and machine learning: challenges and perspective toward enhanced clinical diagnostics","volume":"17","author":"E Aref-Eshghi","year":"2025","journal-title":"Clin Epigenetics"},{"issue":"12","key":"pgen.1012322.ref027","doi-asserted-by":"crossref","first-page":"326","DOI":"10.31083\/j.fbl2712326","article-title":"DNA Methylation: From Cancer Biology to Clinical Perspectives","volume":"27","author":"C Chen","year":"2022","journal-title":"Front Biosci (Landmark Ed)"},{"issue":"2","key":"pgen.1012322.ref028","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2217\/epi.09.33","article-title":"DNA hypomethylation in cancer cells","volume":"1","author":"M Ehrlich","year":"2009","journal-title":"Epigenomics"},{"issue":"10","key":"pgen.1012322.ref029","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1101\/gad.2037511","article-title":"CpG islands and the regulation of transcription","volume":"25","author":"AM Deaton","year":"2011","journal-title":"Genes Dev"},{"issue":"9","key":"pgen.1012322.ref030","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.3390\/cancers12092710","article-title":"Landscape of Genome-Wide DNA Methylation of Colorectal Cancer Metastasis","volume":"12","author":"C Ili","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"2","key":"pgen.1012322.ref031","doi-asserted-by":"crossref","DOI":"10.1016\/j.ccell.2024.01.001","article-title":"Tumor- and circulating-free DNA methylation identifies clinically relevant small cell lung cancer subtypes","volume":"42","author":"S Heeke","year":"2024","journal-title":"Cancer Cell"},{"issue":"1","key":"pgen.1012322.ref032","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1186\/s12916-025-04164-1","article-title":"Molecular signatures of invasive and non-invasive pituitary adenomas: a comprehensive analysis of DNA methylation and gene expression","volume":"23","author":"Y Chen","year":"2025","journal-title":"BMC Med"},{"issue":"8","key":"pgen.1012322.ref033","doi-asserted-by":"crossref","first-page":"996","DOI":"10.3390\/biom14080996","article-title":"Discovery and Validation of Methylation Signatures in Circulating Cell-Free DNA for the Detection of Colorectal Cancer","volume":"14","author":"Z Long","year":"2024","journal-title":"Biomolecules"},{"issue":"14","key":"pgen.1012322.ref034","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.7150\/ijms.95964","article-title":"The PKHD1 gene inhibits tumor proliferation and invasion in intrahepatic cholangiocarcinoma by activating the Notch pathway","volume":"21","author":"T Shang","year":"2024","journal-title":"Int J Med Sci"},{"issue":"3","key":"pgen.1012322.ref035","doi-asserted-by":"crossref","first-page":"675","DOI":"10.20892\/j.issn.2095-3941.2020.0136","article-title":"LncRNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 and predicts poor prognosis in lung cancer patients","volume":"18","author":"H Tian","year":"2021","journal-title":"Cancer Biol Med"},{"key":"pgen.1012322.ref036","doi-asserted-by":"crossref","first-page":"116903","DOI":"10.1016\/j.bcp.2025.116903","article-title":"N6-methyladenosine-modified RNF220 induces cisplatin resistance and immune escape via regulating PDE10A K48-linked ubiquitination in bladder cancer","volume":"236","author":"K Li","year":"2025","journal-title":"Biochem Pharmacol"},{"issue":"44","key":"pgen.1012322.ref037","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adp0631","article-title":"Suppression of non-muscle myosin II boosts T cell cytotoxicity against tumors","volume":"10","author":"Y Yang","year":"2024","journal-title":"Sci Adv"},{"issue":"11","key":"pgen.1012322.ref038","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1002\/ijc.24958","article-title":"Glutamate receptor, ionotropic, kainate 2 silencing by DNA hypermethylation possesses tumor suppressor function in gastric cancer","volume":"126","author":"C-S Wu","year":"2010","journal-title":"Int J Cancer"},{"issue":"1","key":"pgen.1012322.ref039","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3892\/or.2016.5276","article-title":"COL11A1 is overexpressed in gastric cancer tissues and regulates proliferation, migration and invasion of HGC-27 gastric cancer cells in vitro","volume":"37","author":"A Li","year":"2017","journal-title":"Oncol Rep"},{"key":"pgen.1012322.ref040","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-4598-12-1","article-title":"Analysis of colorectal cancers in British Bangladeshi identifies early onset, frequent mucinous histotype and a high prevalence of RBFOX1 deletion","volume":"12","author":"N Sengupta","year":"2013","journal-title":"Mol Cancer"},{"issue":"2","key":"pgen.1012322.ref041","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1054\/bjoc.2001.1888","article-title":"Frequent loss of expression without sequence mutations of the DCC gene in primary gastric cancer","volume":"85","author":"K Sato","year":"2001","journal-title":"Br J Cancer"},{"key":"pgen.1012322.ref042","doi-asserted-by":"crossref","first-page":"740487","DOI":"10.3389\/fcell.2021.740487","article-title":"A Novel Mitochondrial-Related Nuclear Gene Signature Predicts Overall Survival of Lung Adenocarcinoma Patients","volume":"9","author":"X Zhang","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"12","key":"pgen.1012322.ref043","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1002\/humu.23889","article-title":"Expression and functional characterization of missense mutations in ATP8A2 linked to severe neurological disorders","volume":"40","author":"H Choi","year":"2019","journal-title":"Hum Mutat"},{"issue":"1","key":"pgen.1012322.ref044","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00415-019-09579-4","article-title":"ATP8A2-related disorders as recessive cerebellar ataxia","volume":"267","author":"C Guissart","year":"2020","journal-title":"J Neurol"},{"issue":"1","key":"pgen.1012322.ref045","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12967-017-1122-y","article-title":"Individualized analysis reveals CpG sites with methylation aberrations in almost all lung adenocarcinoma tissues","volume":"15","author":"H Yan","year":"2017","journal-title":"J Transl Med"},{"issue":"5","key":"pgen.1012322.ref046","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1245\/s10434-024-15013-5","article-title":"Early Onset Intrahepatic Cholangiocarcinoma: Clinical Characteristics, Oncological Outcomes, and Genomic\/Transcriptomic Features","volume":"31","author":"DI Tsilimigras","year":"2024","journal-title":"Ann Surg Oncol"},{"key":"pgen.1012322.ref047","doi-asserted-by":"crossref","first-page":"15330338241258570","DOI":"10.1177\/15330338241258570","article-title":"A comprehensive prognostic model for colon adenocarcinoma depending on nuclear-mitochondrial-related genes","volume":"23","author":"L Lv","year":"2024","journal-title":"Technol Cancer Res Treat"},{"issue":"1","key":"pgen.1012322.ref048","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s10238-025-01844-3","article-title":"Identification and validation of prognostic genes associated with mitochondrial nuclear genes in gastric cancer","volume":"25","author":"C Fu","year":"2025","journal-title":"Clin Exp Med"},{"issue":"3","key":"pgen.1012322.ref049","first-page":"241","article-title":"Genes involved in development and differentiation are commonly methylated in cancers derived from multiple organs: a single-institutional methylome analysis using 1007 tissue specimens","volume":"38","author":"K Ohara","year":"2017","journal-title":"Carcinogenesis"},{"issue":"4","key":"pgen.1012322.ref050","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.ccr.2014.07.028","article-title":"Gene body methylation can alter gene expression and is a therapeutic target in cancer","volume":"26","author":"X Yang","year":"2014","journal-title":"Cancer Cell"},{"key":"pgen.1012322.ref051","doi-asserted-by":"crossref","first-page":"1807089","DOI":"10.1155\/2020\/1807089","article-title":"Aberrant Methylation and Differential Expression of SLC2A1, TNS4, GAPDH, ATP8A2, and CASZ1 Are Associated with the Prognosis of Lung Adenocarcinoma","volume":"2020","author":"X Wang","year":"2020","journal-title":"Biomed Res Int"},{"key":"pgen.1012322.ref052","doi-asserted-by":"crossref","first-page":"1149622","DOI":"10.3389\/fimmu.2023.1149622","article-title":"Landscapes and mechanisms of CD8+ T cell exhaustion in gastrointestinal cancer","volume":"14","author":"J-T Ding","year":"2023","journal-title":"Front Immunol"},{"issue":"16","key":"pgen.1012322.ref053","doi-asserted-by":"crossref","DOI":"10.1172\/JCI141083","article-title":"SLIT2\/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia","volume":"131","author":"LH Geraldo","year":"2021","journal-title":"J Clin Invest"},{"key":"pgen.1012322.ref054","article-title":"Exploring ZPLD1 as a Prognostic Indicator and Therapeutic Target in Bladder Cancer","author":"Y Chen","year":"2026","journal-title":"Curr Med Chem"},{"issue":"5","key":"pgen.1012322.ref055","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1615\/CritRevEukaryotGeneExpr.2024052788","article-title":"PURPL Promotes M2 Macrophage Polarization in Lung Cancer by Regulating RBM4\/xCT Signaling","volume":"34","author":"J Guo","year":"2024","journal-title":"Crit Rev Eukaryot Gene Expr"},{"issue":"3","key":"pgen.1012322.ref056","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth","volume":"41","author":"KE de Visser","year":"2023","journal-title":"Cancer Cell"},{"issue":"7","key":"pgen.1012322.ref057","doi-asserted-by":"crossref","first-page":"3333","DOI":"10.3390\/ijms26073333","article-title":"Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer","volume":"26","author":"MJ Maturana","year":"2025","journal-title":"Int J Mol Sci"}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1012322","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:35:13Z","timestamp":1792085713000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1012322"}},"subtitle":[],"editor":[{"given":"Sean P.","family":"Curran","sequence":"first","affiliation":[{"name":"University of Southern California","place":["UNITED STATES OF AMERICA"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":57,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1012322","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]}}}