{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:57:04Z","timestamp":1791262624845,"version":"4.1.0"},"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017961","name":"Health Commission of Heilongjiang Province","doi-asserted-by":"publisher","award":["20230404080327"],"award-info":[{"award-number":["20230404080327"]}],"id":[{"id":"10.13039\/100017961","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Stomach adenocarcinoma (STAD), the most prevalent histological subtype of gastric cancer, exhibits high heterogeneity and poor prognosis, posing significant therapeutic challenges. Parthanatos, a distinct form of regulated cell death mediated by poly (ADP-ribose) polymerase-1 (PARP-1), has been implicated in tumor biology and therapeutic resistance; however, the role of parthanatos-associated genes (PRGs) in STAD remains largely unexplored. In this study, we performed a comprehensive multi-omics analysis integrating transcriptomic, genomic, and clinical data from public databases to delineate the molecular landscape of PRGs in STAD. Unsupervised clustering revealed distinct PRG-related molecular subtypes with significant differences in clinical outcomes, immune infiltration profiles, and biological pathway activation. Based on machine learning algorithms, we established and validated a novel PRG-based prognostic signature, which demonstrated robust predictive performance. Moreover, single-cell RNA sequencing and <jats:italic><jats:italic>in vitro<\/jats:italic><\/jats:italic> functional assays were conducted to explore cellular heterogeneity and gene function. Notably, <jats:italic><jats:italic>in vitro<\/jats:italic><\/jats:italic> experiments, including western blot, colony formation, CCK-8, and Transwell assays, confirmed that one key PRG, COL8A1, promotes STAD cell proliferation and migration. Collectively, our findings highlight the clinical and biological significance of PRGs in STAD, offering novel biomarkers and potential therapeutic targets for STAD precision treatment.<\/jats:p>","DOI":"10.1371\/journal.pone.0332988","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T17:35:22Z","timestamp":1758908122000},"page":"e0332988","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Multi-omics analysis of parthanatos related molecular subgroup and prognostic model development in stomach adenocarcinoma"],"prefix":"10.1371","volume":"20","author":[{"given":"Xiangxin","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianming","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9797-9639","authenticated-orcid":true,"given":"Tianyi","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"issue":"11","key":"pone.0332988.ref001","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMicm2413107","article-title":"Gastric Adenocarcinoma and Proximal Polyposis of the Stomach","volume":"392","author":"K Tanaka","year":"2025","journal-title":"N Engl J Med"},{"issue":"7","key":"pone.0332988.ref002","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s41571-023-00767-w","article-title":"Early stage gastric adenocarcinoma: clinical and molecular landscapes","volume":"20","author":"Y Hirata","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"issue":"9","key":"pone.0332988.ref003","doi-asserted-by":"crossref","DOI":"10.1016\/S1470-2045(24)00180-3","article-title":"Improving individualised therapies in localised gastro-oesophageal adenocarcinoma","volume":"25","author":"M Svrcek","year":"2024","journal-title":"Lancet Oncol"},{"key":"pone.0332988.ref004","doi-asserted-by":"crossref","first-page":"113370","DOI":"10.1016\/j.ejca.2023.113370","article-title":"Treatment of gastric adenocarcinoma: A rapidly evolving landscape","volume":"195","author":"J Taieb","year":"2023","journal-title":"Eur J Cancer"},{"issue":"3","key":"pone.0332988.ref005","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-010024","article-title":"Comprehensive immunophenotyping of gastric adenocarcinoma identifies an inflamed class of tumors amenable to immunotherapies","volume":"13","author":"J Veas Rodriguez","year":"2025","journal-title":"J Immunother Cancer"},{"issue":"3","key":"pone.0332988.ref006","first-page":"264","article-title":"Current treatment and recent progress in gastric cancer","volume":"71","author":"SS Joshi","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"35","key":"pone.0332988.ref007","doi-asserted-by":"crossref","DOI":"10.1002\/adfm.202506476","article-title":"Zn\u2010DHM Nanozymes Enhance Muscle Regeneration Through ROS Scavenging and Macrophage Polarization in Volumetric Muscle Loss Revealed by Single\u2010Cell Profiling","volume":"35","author":"X Feng","year":"2025","journal-title":"Adv Funct Materials"},{"issue":"7","key":"pone.0332988.ref008","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41575-022-00591-0","article-title":"The immune microenvironment in gastric adenocarcinoma","volume":"19","author":"Y Zavros","year":"2022","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"pone.0332988.ref009","doi-asserted-by":"crossref","first-page":"102418","DOI":"10.1016\/j.ctrv.2022.102418","article-title":"Resistance mechanisms to HER2-targeted therapy in gastroesophageal adenocarcinoma: A systematic review","volume":"108","author":"D Blang\u00e9","year":"2022","journal-title":"Cancer Treat Rev"},{"key":"pone.0332988.ref010","doi-asserted-by":"crossref","first-page":"101002","DOI":"10.1016\/j.drup.2023.101002","article-title":"Treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs","volume":"71","author":"P Xing","year":"2023","journal-title":"Drug Resist Updat"},{"key":"pone.0332988.ref011","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1196\/annals.1427.014","article-title":"Mitochondrial and nuclear cross talk in cell death: parthanatos","volume":"1147","author":"SA Andrabi","year":"2008","journal-title":"Ann N Y Acad Sci"},{"key":"pone.0332988.ref012","doi-asserted-by":"crossref","first-page":"101239","DOI":"10.1016\/j.redox.2019.101239","article-title":"Programmed necrotic cell death of macrophages: Focus on pyroptosis, necroptosis, and parthanatos","volume":"26","author":"N Robinson","year":"2019","journal-title":"Redox Biol"},{"issue":"5579","key":"pone.0332988.ref013","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1126\/science.1072221","article-title":"Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor","volume":"297","author":"S-W Yu","year":"2002","journal-title":"Science"},{"issue":"6308","key":"pone.0332988.ref014","doi-asserted-by":"crossref","DOI":"10.1126\/science.aad6872","article-title":"A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1","volume":"354","author":"Y Wang","year":"2016","journal-title":"Science"},{"issue":"3","key":"pone.0332988.ref015","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1046\/j.1365-2567.1998.00534.x","article-title":"Peroxynitrite-induced thymocyte apoptosis: the role of caspases and poly (ADP-ribose) synthetase (PARS) activation","volume":"94","author":"L Vir\u00e1g","year":"1998","journal-title":"Immunology"},{"issue":"7","key":"pone.0332988.ref016","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.4049\/jimmunol.161.7.3753","article-title":"Poly(ADP-ribose) synthetase activation mediates mitochondrial injury during oxidant-induced cell death","volume":"161","author":"L Vir\u00e1g","year":"1998","journal-title":"J Immunol"},{"issue":"4","key":"pone.0332988.ref017","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/S0026-895X(24)12546-1","article-title":"Requirement of intracellular calcium mobilization for peroxynitrite-induced poly(ADP-ribose) synthetase activation and cytotoxicity","volume":"56","author":"L Vir\u00e1\u0123","year":"1999","journal-title":"Mol Pharmacol"},{"issue":"8","key":"pone.0332988.ref018","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/S0891-5849(00)00359-2","article-title":"BCL-2 protects peroxynitrite-treated thymocytes from poly(ADP-ribose) synthase (PARS)-independent apoptotic but not from PARS-mediated necrotic cell death","volume":"29","author":"L Vir\u00e1g","year":"2000","journal-title":"Free Radic Biol Med"},{"issue":"1","key":"pone.0332988.ref019","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1080\/10409238.2017.1394265","article-title":"Specificity of reversible ADP-ribosylation and regulation of cellular processes","volume":"53","author":"K Crawford","year":"2018","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"pone.0332988.ref020","doi-asserted-by":"crossref","first-page":"105299","DOI":"10.1016\/j.phrs.2020.105299","article-title":"Parthanatos and its associated components: Promising therapeutic targets for cancer","volume":"163","author":"Y Zhou","year":"2021","journal-title":"Pharmacol Res"},{"issue":"11","key":"pone.0332988.ref021","doi-asserted-by":"crossref","first-page":"6313","DOI":"10.1093\/nar\/gkac471","article-title":"KDM6B promotes PARthanatos via suppression of O6-methylguanine DNA methyltransferase repair and sustained checkpoint response","volume":"50","author":"M Yang","year":"2022","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0332988.ref022","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41421-022-00504-0","article-title":"A RIPK3-independent role of MLKL in suppressing parthanatos promotes immune evasion in hepatocellular carcinoma","volume":"9","author":"X Jiang","year":"2023","journal-title":"Cell Discov"},{"issue":"1","key":"pone.0332988.ref023","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12964-022-00897-1","article-title":"Inhibition of AKT induces p53\/SIRT6\/PARP1-dependent parthanatos to suppress tumor growth","volume":"20","author":"Y Zhang","year":"2022","journal-title":"Cell Commun Signal"},{"key":"pone.0332988.ref024","first-page":"351","article-title":"Parthanatos and apoptosis: unraveling their roles in cancer cell death and therapy resistance","volume":"24","author":"G Gupta","year":"2025","journal-title":"EXCLI J"},{"issue":"9","key":"pone.0332988.ref025","doi-asserted-by":"crossref","first-page":"101191","DOI":"10.1016\/j.xcrm.2023.101191","article-title":"PARP-1 improves leukemia outcomes by inducing parthanatos during chemotherapy","volume":"4","author":"B Maru","year":"2023","journal-title":"Cell Rep Med"},{"issue":"10","key":"pone.0332988.ref026","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/s41580-023-00615-w","article-title":"The technological landscape and applications of single-cell multi-omics","volume":"24","author":"A Baysoy","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"pone.0332988.ref027","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41746-024-01043-6","article-title":"Informing immunotherapy with multi-omics driven machine learning","volume":"7","author":"Y Li","year":"2024","journal-title":"NPJ Digit Med"},{"key":"pone.0332988.ref028","doi-asserted-by":"crossref","DOI":"10.1093\/burnst\/tkac050","article-title":"Prospective study and validation of early warning marker discovery based on integrating multi-omics analysis in severe burn patients with sepsis","volume":"11","author":"J Huang","year":"2023","journal-title":"Burns Trauma"},{"issue":"3","key":"pone.0332988.ref029","article-title":"Macrophage differentiation in enhancing hematopoietic function of ribonucleic acid for injection II via multi-omics analysis","volume":"3","author":"Y Li","year":"2024","journal-title":"Acta Materia Medica"},{"key":"pone.0332988.ref030","doi-asserted-by":"crossref","first-page":"1522655","DOI":"10.3389\/fimmu.2024.1522655","article-title":"Single-cell RNA sequencing and immune microenvironment analysis reveal PLOD2-driven malignant transformation in cervical cancer","volume":"15","author":"Z Lin","year":"2025","journal-title":"Front Immunol"},{"issue":"1","key":"pone.0332988.ref031","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1186\/s12967-023-04633-2","article-title":"Integrated machine learning identifies epithelial cell marker genes for improving outcomes and immunotherapy in prostate cancer","volume":"21","author":"W Zhu","year":"2023","journal-title":"J Transl Med"},{"issue":"9","key":"pone.0332988.ref032","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1136\/gutjnl-2019-318640","article-title":"USF1 defect drives p53 degradation during Helicobacter pylori infection and accelerates gastric carcinogenesis","volume":"69","author":"L Costa","year":"2020","journal-title":"Gut"},{"issue":"22","key":"pone.0332988.ref033","article-title":"Chitosan-Gelatin-EGCG Nanoparticle-Meditated LncRNA TMEM44-AS1 Silencing to Activate the P53 Signaling Pathway for the Synergistic Reversal of 5-FU Resistance in Gastric Cancer","volume":"9","author":"M Zhou","year":"2022","journal-title":"Adv Sci (Weinh)"},{"issue":"1","key":"pone.0332988.ref034","doi-asserted-by":"crossref","first-page":"5006","DOI":"10.1038\/s41467-025-60144-2","article-title":"Cleavage of CAD by caspase-3 determines the cancer cell fate during chemotherapy","volume":"16","author":"J Ma","year":"2025","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0332988.ref035","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3390\/ijms24010016","article-title":"Resolution Potential of Necrotic Cell Death Pathways","volume":"24","author":"A M\u00e1zl\u00f3","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"6","key":"pone.0332988.ref036","doi-asserted-by":"crossref","first-page":"5471","DOI":"10.18632\/aging.205658","article-title":"Integrated single-cell sequencing, spatial transcriptome sequencing and bulk RNA sequencing highlights the molecular characteristics of parthanatos in gastric cancer","volume":"16","author":"X Qiao","year":"2024","journal-title":"Aging (Albany NY)"},{"issue":"1","key":"pone.0332988.ref037","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1007\/s12672-024-01411-4","article-title":"Integrative analysis of multiple cell death model for precise prognosis and drug response prediction in gastric cancer","volume":"15","author":"W Su","year":"2024","journal-title":"Discov Oncol"},{"issue":"8","key":"pone.0332988.ref038","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/s41580-025-00842-3","article-title":"p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases","volume":"26","author":"Y Liu","year":"2025","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"pone.0332988.ref039","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/s41392-022-01110-y","article-title":"Regulated cell death (RCD) in cancer: key pathways and targeted therapies","volume":"7","author":"F Peng","year":"2022","journal-title":"Signal Transduct Target Ther"},{"issue":"6","key":"pone.0332988.ref040","doi-asserted-by":"crossref","first-page":"373","DOI":"10.4161\/gmic.1.6.13572","article-title":"Helicobacter pylori activation of PARP-1: usurping a versatile regulator of host cellular health","volume":"1","author":"CW Nossa","year":"2010","journal-title":"Gut Microbes"},{"issue":"1","key":"pone.0332988.ref041","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/BF03256428","article-title":"PARP1 polymorphisms increase the risk of gastric cancer in a Chinese population","volume":"16","author":"W He","year":"2012","journal-title":"Mol Diagn Ther"},{"issue":"8","key":"pone.0332988.ref042","doi-asserted-by":"crossref","first-page":"152472","DOI":"10.1016\/j.prp.2019.152472","article-title":"PARP1: A potential biomarker for gastric cancer","volume":"215","author":"H Afzal","year":"2019","journal-title":"Pathol Res Pract"},{"key":"pone.0332988.ref043","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.biocel.2017.08.001","article-title":"Inhibition of PARP1 activity enhances chemotherapeutic efficiency in cisplatin-resistant gastric cancer cells","volume":"92","author":"Q Wang","year":"2017","journal-title":"Int J Biochem Cell Biol"},{"key":"pone.0332988.ref044","doi-asserted-by":"crossref","first-page":"103278","DOI":"10.1016\/j.dnarep.2022.103278","article-title":"TOPBP1 regulates resistance of gastric cancer to oxaliplatin by promoting transcription of PARP1","volume":"111","author":"Z Fang","year":"2022","journal-title":"DNA Repair (Amst)"},{"issue":"3","key":"pone.0332988.ref045","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00018-022-04129-0","article-title":"METTL3 promotes oxaliplatin resistance of gastric cancer CD133+\u2009stem cells by promoting PARP1 mRNA stability","volume":"79","author":"H Li","year":"2022","journal-title":"Cell Mol Life Sci"},{"issue":"2","key":"pone.0332988.ref046","doi-asserted-by":"crossref","DOI":"10.1111\/jcmm.18033","article-title":"Ailanthone synergizes with PARP1 inhibitor in tumour growth inhibition through crosstalk of DNA repair pathways in gastric cancer","volume":"28","author":"C Wang","year":"2024","journal-title":"J Cell Mol Med"},{"issue":"3","key":"pone.0332988.ref047","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.13373","article-title":"Identifying the key genes of Epstein-Barr virus-regulated tumour immune microenvironment of gastric carcinomas","volume":"56","author":"H Zhou","year":"2023","journal-title":"Cell Prolif"},{"issue":"1","key":"pone.0332988.ref048","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.jhep.2025.02.039","article-title":"Hot and cold fibrosis: The role of serum biomarkers to assess immune mechanisms and ECM-cell interactions in human fibrosis","volume":"83","author":"A de Zawadzki","year":"2025","journal-title":"J Hepatol"},{"issue":"1","key":"pone.0332988.ref049","doi-asserted-by":"crossref","first-page":"2189295","DOI":"10.1080\/07853890.2023.2189295","article-title":"Targeting GPC3high cancer-associated fibroblasts sensitizing the PD-1 blockage therapy in gastric cancer","volume":"55","author":"D Li","year":"2023","journal-title":"Ann Med"},{"issue":"1","key":"pone.0332988.ref050","doi-asserted-by":"crossref","first-page":"23328","DOI":"10.1038\/s41598-024-74907-2","article-title":"Machine learning based intratumor heterogeneity signature for predicting prognosis and immunotherapy benefit in stomach adenocarcinoma","volume":"14","author":"H Chen","year":"2024","journal-title":"Sci Rep"},{"key":"pone.0332988.ref051","doi-asserted-by":"crossref","first-page":"1569988","DOI":"10.3389\/fimmu.2025.1569988","article-title":"Single-cell atlas of endothelial cells in atherosclerosis: identifying C1 CXCL12+ ECs as key proliferative drivers for immunological precision therapeutics in atherosclerosis","volume":"16","author":"Z Zhao","year":"2025","journal-title":"Front Immunol"},{"key":"pone.0332988.ref052","doi-asserted-by":"crossref","first-page":"1584350","DOI":"10.3389\/fimmu.2025.1584350","article-title":"Decoding multiple myeloma: single-cell insights into tumor heterogeneity, immune dynamics, and disease progression","volume":"16","author":"Z Zhao","year":"2025","journal-title":"Front Immunol"},{"issue":"5","key":"pone.0332988.ref053","article-title":"Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer","volume":"57","author":"R Ma","year":"2024","journal-title":"Cell Prolif"},{"issue":"3","key":"pone.0332988.ref054","article-title":"Prognostic Value of Tumor-microenvironment-associated Genes in Ovarian Cancer","volume":"4","author":"S Li","year":"2022","journal-title":"BIOI"},{"issue":"3","key":"pone.0332988.ref055","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s10585-019-09966-1","article-title":"The extracellular matrix in tumor progression and metastasis","volume":"36","author":"JA Eble","year":"2019","journal-title":"Clin Exp Metastasis"},{"issue":"1","key":"pone.0332988.ref056","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/s43018-021-00291-9","article-title":"A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy","volume":"3","author":"JS Di Martino","year":"2022","journal-title":"Nat Cancer"},{"issue":"8","key":"pone.0332988.ref057","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1158\/2159-8290.CD-24-0002","article-title":"The Interplay between Extracellular Matrix Remodeling and Cancer Therapeutics","volume":"14","author":"J Prakash","year":"2024","journal-title":"Cancer Discov"},{"issue":"1","key":"pone.0332988.ref058","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12943-023-01744-8","article-title":"Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments","volume":"22","author":"Z Yuan","year":"2023","journal-title":"Mol Cancer"},{"issue":"3","key":"pone.0332988.ref059","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/bjc.2017.458","article-title":"A core matrisome gene signature predicts cancer outcome","volume":"118","author":"AE Yuzhalin","year":"2018","journal-title":"Br J Cancer"},{"issue":"10","key":"pone.0332988.ref060","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1039\/C8BM00843D","article-title":"Increased extracellular matrix density disrupts E-cadherin\/\u03b2-catenin complex in gastric cancer cells","volume":"6","author":"M Jang","year":"2018","journal-title":"Biomater Sci"},{"issue":"3","key":"pone.0332988.ref061","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3390\/cells11030349","article-title":"Mast Cell-Tumor Interactions: Molecular Mechanisms of Recruitment, Intratumoral Communication and Potential Therapeutic Targets for Tumor Growth","volume":"11","author":"D Segura-Villalobos","year":"2022","journal-title":"Cells"},{"issue":"11","key":"pone.0332988.ref062","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.3390\/ijms17111905","article-title":"Mast Cells Density Positive to Tryptase Correlate with Microvascular Density in both Primary Gastric Cancer Tissue and Loco-Regional Lymph Node Metastases from Patients That Have Undergone Radical Surgery","volume":"17","author":"M Ammendola","year":"2016","journal-title":"Int J Mol Sci"},{"issue":"9","key":"pone.0332988.ref063","article-title":"Intratumor IL-17-positive mast cells are the major source of the IL-17 that is predictive of survival in gastric cancer patients","volume":"9","author":"X Liu","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"pone.0332988.ref064","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s40425-019-0530-3","article-title":"Increased intratumoral mast cells foster immune suppression and gastric cancer progression through TNF-\u03b1-PD-L1 pathway","volume":"7","author":"Y Lv","year":"2019","journal-title":"J Immunother Cancer"},{"issue":"1","key":"pone.0332988.ref065","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s101200050017","article-title":"Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis","volume":"2","author":"H Yano","year":"1999","journal-title":"Gastric Cancer"},{"issue":"1","key":"pone.0332988.ref066","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1038\/s41467-019-10676-1","article-title":"IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization","volume":"10","author":"MF Eissmann","year":"2019","journal-title":"Nat Commun"},{"key":"pone.0332988.ref067","doi-asserted-by":"crossref","first-page":"111712","DOI":"10.1016\/j.cellsig.2025.111712","article-title":"LPAR3 and COL8A1, as matrix stiffness-related biomarkers, promote nasopharyngeal carcinoma metastasis by triggering EMT and angiogenesis","volume":"131","author":"L Yi","year":"2025","journal-title":"Cell Signal"},{"issue":"1","key":"pone.0332988.ref068","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1186\/s12943-024-02180-y","article-title":"THBS2\u2009+\u2009cancer-associated fibroblasts promote EMT leading to oxaliplatin resistance via COL8A1-mediated PI3K\/AKT activation in colorectal cancer","volume":"23","author":"X Zhou","year":"2024","journal-title":"Mol Cancer"},{"issue":"5","key":"pone.0332988.ref069","doi-asserted-by":"crossref","first-page":"3502","DOI":"10.1245\/s10434-023-14370-x","article-title":"COL8A1 Regulates Esophageal Squamous Carcinoma Proliferation and Invasion Through PI3K\/AKT Pathway","volume":"31","author":"J Hu","year":"2024","journal-title":"Ann Surg Oncol"},{"issue":"4","key":"pone.0332988.ref070","first-page":"34","article-title":"Upregulation of COL8A1 indicates poor prognosis across human cancer types and promotes the proliferation of gastric cancer cells","volume":"20","author":"J Zhou","year":"2020","journal-title":"Oncol Lett"},{"key":"pone.0332988.ref071","doi-asserted-by":"crossref","first-page":"7567447","DOI":"10.1155\/2022\/7567447","article-title":"COL8A1 Predicts the Clinical Prognosis of Gastric Cancer and Is Related to Epithelial-Mesenchymal Transition","volume":"2022","author":"Y She","year":"2022","journal-title":"Biomed Res Int"},{"issue":"3","key":"pone.0332988.ref072","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.3390\/ijms25031848","article-title":"Targeting PI3K\/AKT\/mTOR and MAPK Signaling Pathways in Gastric Cancer","volume":"25","author":"D-T Morgos","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"8","key":"pone.0332988.ref073","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2023.e18945","article-title":"Helicobacter pylori and epithelial mesenchymal transition in human gastric cancers: An update of the literature","volume":"9","author":"TM Jamal Eddin","year":"2023","journal-title":"Heliyon"},{"issue":"10","key":"pone.0332988.ref074","doi-asserted-by":"crossref","first-page":"793","DOI":"10.3390\/cells13100793","article-title":"Single-Cell Analyses Offer Insights into the Different Remodeling Programs of Arteries and Veins","volume":"13","author":"MG Rojas","year":"2024","journal-title":"Cells"},{"key":"pone.0332988.ref075","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.matbio.2024.08.006","article-title":"Collagen VIII in vascular diseases","volume":"133","author":"Q Li","year":"2024","journal-title":"Matrix Biol"},{"key":"pone.0332988.ref076","doi-asserted-by":"crossref","first-page":"641763","DOI":"10.3389\/fcell.2021.641763","article-title":"Platelet-Derived Extracellular Vesicles Increase Col8a1 Secretion and Vascular Stiffness in Intimal Injury","volume":"9","author":"H Bao","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"2","key":"pone.0332988.ref077","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1007\/s10120-021-01259-5","article-title":"Cancer-associated fibroblasts-derived HAPLN1 promotes tumour invasion through extracellular matrix remodeling in gastric cancer","volume":"25","author":"T Zhang","year":"2022","journal-title":"Gastric Cancer"},{"issue":"47","key":"pone.0332988.ref078","article-title":"Gastric Cancer Actively Remodels Mechanical Microenvironment to Promote Chemotherapy Resistance via MSCs-Mediated Mitochondrial Transfer","volume":"11","author":"X He","year":"2024","journal-title":"Adv Sci (Weinh)"},{"issue":"12","key":"pone.0332988.ref079","doi-asserted-by":"crossref","first-page":"6711","DOI":"10.21873\/anticanres.13886","article-title":"Prognostic Significance of LC3B and p62\/SQSTM1 Expression in Gastric Adenocarcinoma","volume":"39","author":"JS Kim","year":"2019","journal-title":"Anticancer Res"},{"issue":"1","key":"pone.0332988.ref080","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s12885-017-3055-5","article-title":"Gastrin activates autophagy and increases migration and survival of gastric adenocarcinoma cells","volume":"17","author":"SV Rao","year":"2017","journal-title":"BMC Cancer"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0332988","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T17:35:36Z","timestamp":1758908136000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0332988"}},"subtitle":[],"editor":[{"given":"Jin Su","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,26]]},"references-count":80,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0332988","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,26]]}}}