{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:22:55Z","timestamp":1790821375778,"version":"4.1.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\nBackground<\/jats:title>\nGastric cancer is a leading cause of cancer-related mortality worldwide, with poor survival outcomes despite advances in diagnostic and therapeutic methods. Mitochondrial autophagy, or mitophagy, is crucial for maintaining cellular homeostasis and has significant implications in tumor biology. DUSP1, a bispecific phosphatase regulating MAP kinase activity, has been associated with various cancers, but its role in GC remains unclear.<\/jats:p>\n<\/jats:sec>\n\nMaterials and methods<\/jats:title>\nIn order to gain a deeper understanding of gastric cancer cells, this study utilized bulk RNA-seq data from TCGA and GEO, combined with the MSigDB database, to screen for mitophagy-related genes. Univariate Cox regression and LASSO analysis were employed to further identify key mitophagy-related genes. Single-cell RNA sequencing data from the database was analyzed using Seurat software to investigate the mitochondrial autophagy genes in each candidate gastric tissue. To clarify the functional pathways involved, enrichment analysis and differential gene expression analysis were conducted. The characteristics of the immune microenvironment were assessed using the CIBERSORT R package. Additionally, both the ssGSEA algorithm and the CIBERSORT algorithm were utilized to evaluate changes and effects in immunological characteristics during gastric cancer pathogenesis.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nWe identified eight prognostic genes\u2014STX10, CDC37, VPS35, RCAN1, TRIM25, DUSP1, SEC23A, and GLT8D1\u2014using LASSO-Cox regression analysis. RCAN1 and DUSP1 are strongly positively correlated, while DUSP1 is strongly negatively correlated with TRIM25, and CDC37 is strongly negatively correlated with SEC23A. By incorporating mitochondrial autophagy scores and clinical characteristics, we established a prognostic model that accurately predicts the 3-year survival status of gastric cancer (GC) patients. Additionally, our single-cell analysis identified DUSP1 as a key mitophagy-related gene. Functional studies demonstrated that DUSP1 knockdown significantly inhibits GC cell proliferation and migration.<\/jats:p>\n<\/jats:sec>\n\nConclusion<\/jats:title>\nIn this study, we developed a risk score based on eight mitochondrial autophagy-related genes and analyzed their expression across different cell types using single-cell analysis. DUSP1 stood out as a key player in gastric cancer progression, with higher expression in tumor tissues and a significant role in cell proliferation, apoptosis, and drug resistance. Our research also linked this risk score to tumor microenvironment immune cell infiltration and tumor mutational burden, revealing distinct high and low-risk groups in gastric cancer patients. This risk score holds potential for improving patient survival assessment and guiding personalized treatment, including enhancing immunotherapy efficacy.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0325520","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T17:36:53Z","timestamp":1749490613000},"page":"e0325520","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Utilizing Multi-omics analysis to elucidate the role of mitochondrial gene defects in Gastric cancer progression"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4497-4782","authenticated-orcid":true,"given":"Jie","family":"Chu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanying","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kemin","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiudong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixin","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"pone.0325520.ref001","doi-asserted-by":"crossref","first-page":"956190","DOI":"10.3389\/fonc.2022.956190","article-title":"Metformin-induced AMPK activation promotes cisplatin resistance through PINK1\/Parkin dependent mitophagy in gastric cancer","volume":"12","author":"Y-Y Xiao","year":"2022","journal-title":"Front Oncol"},{"key":"pone.0325520.ref002","doi-asserted-by":"crossref","first-page":"885553","DOI":"10.3389\/fgene.2022.885553","article-title":"Development of a Novel Immune-Related Gene Signature to Predict Prognosis and Immunotherapeutic Efficiency in Gastric Cancer","volume":"13","author":"D Liu","year":"2022","journal-title":"Front Genet"},{"issue":"12","key":"pone.0325520.ref003","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.13327","article-title":"Mitophagy: A novel perspective for insighting into cancer and cancer treatment","volume":"55","author":"C Song","year":"2022","journal-title":"Cell Prolif"},{"issue":"24","key":"pone.0325520.ref004","doi-asserted-by":"crossref","first-page":"7191","DOI":"10.1158\/0008-5472.CAN-14-1379","article-title":"DUSP1 phosphatase regulates the proinflammatory milieu in head and neck squamous cell carcinoma","volume":"74","author":"X Zhang","year":"2014","journal-title":"Cancer Res"},{"issue":"3","key":"pone.0325520.ref005","first-page":"1203","article-title":"DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer","volume":"40","author":"F Teng","year":"2018","journal-title":"Oncol Rep"},{"issue":"8","key":"pone.0325520.ref006","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1002\/cam4.772","article-title":"Role of DUSP1\/MKP1 in tumorigenesis, tumor progression and therapy","volume":"5","author":"J Shen","year":"2016","journal-title":"Cancer Med"},{"key":"pone.0325520.ref007","doi-asserted-by":"crossref","first-page":"802528","DOI":"10.3389\/fcell.2021.802528","article-title":"Mitophagy-Related Gene Signature for Prediction Prognosis, Immune Scenery, Mutation, and Chemotherapy Response in Pancreatic Cancer","volume":"9","author":"Z Zhuo","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"11","key":"pone.0325520.ref008","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1101\/gr.239244.118","article-title":"Maftools: efficient and comprehensive analysis of somatic variants in cancer","volume":"28","author":"A Mayakonda","year":"2018","journal-title":"Genome Res"},{"issue":"1","key":"pone.0325520.ref009","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s40880-019-0427-z","article-title":"The immune landscape of esophageal cancer","volume":"39","author":"T-X Huang","year":"2019","journal-title":"Cancer Commun (Lond)"},{"issue":"12","key":"pone.0325520.ref010","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/emmm.201100801","article-title":"DNA methylation profiling reveals a predominant immune component in breast cancers","volume":"3","author":"S Dedeurwaerder","year":"2011","journal-title":"EMBO Mol Med"},{"issue":"2","key":"pone.0325520.ref011","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1093\/annonc\/mds280","article-title":"Genomic grade adds prognostic value in invasive lobular carcinoma","volume":"24","author":"O Metzger-Filho","year":"2013","journal-title":"Ann Oncol"},{"key":"pone.0325520.ref012","doi-asserted-by":"crossref","DOI":"10.1093\/database\/baq020","article-title":"GeneCards Version 3: the human gene integrator","volume":"2010","author":"M Safran","year":"2010","journal-title":"Database (Oxford)"},{"issue":"6","key":"pone.0325520.ref013","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"A Liberzon","year":"2015","journal-title":"Cell Syst"},{"issue":"1","key":"pone.0325520.ref014","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization Paths for Generalized Linear Models via Coordinate Descent","volume":"33","author":"J Friedman","year":"2010","journal-title":"J Stat Softw"},{"key":"pone.0325520.ref015","article-title":"20 years and still going strong","volume":"47","author":"The gene ontology resource","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0325520.ref016","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"M Ashburner","year":"2000","journal-title":"Nat Genet"},{"issue":"1","key":"pone.0325520.ref017","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/nar\/27.1.29","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"27","author":"H Ogata","year":"1999","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"pone.0325520.ref018","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"Clusterprofiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"G Yu","year":"2012","journal-title":"OMICS"},{"issue":"3","key":"pone.0325520.ref019","first-page":"100141","article-title":"clusterProfiler 4. 0: A universal enrichment tool for interpreting omics data","volume":"2","author":"T Wu","year":"2021","journal-title":"Innovation (Camb)"},{"issue":"17","key":"pone.0325520.ref020","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1093\/bioinformatics\/btv300","article-title":"GOplot: an R package for visually combining expression data with functional analysis","volume":"31","author":"W Walter","year":"2015","journal-title":"Bioinformatics"},{"issue":"43","key":"pone.0325520.ref021","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0325520.ref022","article-title":"Pan-Cancer Single-Cell Analysis Revealing the Heterogeneity of Cancer-Associated Fibroblasts in Skin Tumors","author":"Y Zhang","year":"2024","journal-title":"Curr Gene Ther"},{"key":"pone.0325520.ref023","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"S H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinformatics"},{"issue":"7","key":"pone.0325520.ref024","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"ME Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"pone.0325520.ref025","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","article-title":"Determining cell type abundance and expression from bulk tissues with digital cytometry","volume":"37","author":"AM Newman","year":"2019","journal-title":"Nat Biotechnol"},{"key":"pone.0325520.ref026","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":"7","key":"pone.0325520.ref027","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/cac2.12067","article-title":"A nomogram for predicting overall survival in patients with low-grade endometrial stromal sarcoma: A population-based analysis","volume":"40","author":"J Wu","year":"2020","journal-title":"Cancer Commun (Lond)"},{"issue":"3","key":"pone.0325520.ref028","doi-asserted-by":"crossref","first-page":"898","DOI":"10.7150\/jca.102045","article-title":"Single-cell analysis unveils cell subtypes of acral melanoma cells at the early and late differentiation stages","volume":"16","author":"M Hou","year":"2025","journal-title":"J Cancer"},{"issue":"8","key":"pone.0325520.ref029","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/s41580-023-00585-z","article-title":"Autophagy and autophagy-related pathways in cancer","volume":"24","author":"J Debnath","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"pone.0325520.ref030","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12943-022-01616-7","article-title":"Wnt signaling in colorectal cancer: pathogenic role and therapeutic target","volume":"21","author":"H Zhao","year":"2022","journal-title":"Mol Cancer"},{"issue":"21","key":"pone.0325520.ref031","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1056\/NEJMra1704560","article-title":"Phosphatidylinositol 3-Kinase, Growth Disorders, and Cancer","volume":"379","author":"MD Goncalves","year":"2018","journal-title":"N Engl J Med"},{"key":"pone.0325520.ref032","doi-asserted-by":"crossref","first-page":"119499","DOI":"10.1016\/j.lfs.2021.119499","article-title":"Interplay between MAPK\/ERK signaling pathway and MicroRNAs: A crucial mechanism regulating cancer cell metabolism and tumor progression","volume":"278","author":"ER Asl","year":"2021","journal-title":"Life Sci"},{"issue":"6","key":"pone.0325520.ref033","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/onc.2010.449","article-title":"DUSP1\/MKP1 promotes angiogenesis, invasion and metastasis in non-small-cell lung cancer","volume":"30","author":"V Moncho-Amor","year":"2011","journal-title":"Oncogene"},{"issue":"1","key":"pone.0325520.ref034","doi-asserted-by":"crossref","first-page":"288","DOI":"10.7150\/jca.101420","article-title":"The cellular signaling crosstalk between memory B cells and tumor cells in nasopharyngeal carcinoma cannot be overlooked: Their involvement in tumor progression and treatment strategy is significant","volume":"16","author":"H Li","year":"2025","journal-title":"J Cancer"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0325520","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T17:37:04Z","timestamp":1749490624000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0325520"}},"subtitle":[],"editor":[{"given":"Zhiheng","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":34,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0325520","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]}}}