{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:48:59Z","timestamp":1792586939156,"version":"4.5.0"},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":293,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chemotherapy is the mainstay of systemic treatment for colorectal cancer (CRC), but drug resistance and tumor heterogeneity markedly limit survival. Mitochondrial metabolism is increasingly recognized as a regulator of tumor progression, immune contexture, and therapeutic response. However, the prognostic relevance of mitochondrial metabolism\u2013related transcriptional patterns and their relationships with chemotherapy\u2010response signatures and immune features in CRC remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical and transcriptomic data from The Cancer Genome Atlas colorectal cancer cohort (TCGA\u2010CRC) and Gene Expression Omnibus cohorts GSE17537 and GSE104645 were analyzed. A curated set of mitochondrial metabolism\u2013related genes (MMRGs) were used to calculate an MMRG score, whereas genes upregulated in chemotherapy\u2010sensitive cases in GSE104645 were used to derive a drug\u2010sensitivity gene\u2010set score by single\u2010sample gene set enrichment analysis (ssGSEA). Weighted gene coexpression network analysis (WGCNA), differential expression analysis, univariate Cox regression, least absolute shrinkage and selection operator regression, and multivariate Cox regression were used to construct a five\u2010gene RiskScore. Prognostic associations were assessed using Kaplan\u2013Meier curves, time\u2010dependent receiver operating characteristic curves, external validation, and subgroup analyses. Immune\u2010cell enrichment and pRRophetic\u2010predicted half\u2010maximal inhibitory concentration values were evaluated, and CD36 was examined using in vitro phenotypic assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tumors showed lower MMRG scores than normal tissues, and higher MMRG scores were associated with better overall survival (OS). The drug\u2010sensitivity gene\u2010set score was higher in tumors but was not significantly associated with OS. A five\u2010gene signature (CD36, CPA3, FCRL2, POU2F2, and S100B) generated a RiskScore that separated OS outcomes in the TCGA training, testing, and overall cohorts, as well as GSE17537, although its time\u2010dependent discrimination varied across cohorts and follow\u2010up periods. Similar survival associations were observed within subgroups defined by stage, age, and sex; however, independent or incremental prognostic value was not evaluated. High\u2010risk tumors exhibited altered immune\u2010cell enrichment, and the RiskScore was correlated with pRRophetic\u2010predicted drug IC50 values after Benjamini\u2013Hochberg correction. CD36 expression was higher in SW1116 than in NCM460 cells, and its knockdown inhibited proliferation, migration, and invasion. Mitochondrial function was not directly measured in these experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The five\u2010gene RiskScore was associated with OS, immune\u2010cell enrichment, and in silico drug\u2010sensitivity estimates in CRC. It may serve as a candidate tool for prognostic stratification, but its incremental clinical value and treatment\u2010predictive utility require prospective validation. The CD36 knockdown experiments support a tumor\u2010promoting phenotype in SW1116 cells but do not establish dependence on mitochondrial metabolic reprogramming.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/5519367","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:32:02Z","timestamp":1792585922000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Immuno\u2010Diagnostic and Therapeutic Markers in Tumors and Inflammatory Diseases Based on Single\u2010Cell and Machine Learning Methods"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2930-627X","authenticated-orcid":false,"given":"Jinfen","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology Ningbo No.2 Hospital Wenzhou Medical University  Ningbo City Zhejiang Province China  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