Pan-Cancer Analyses of Shared and Distinct Gene Expression in 17 Cancers: Rethinking Cancer Classification and Moving Beyond One Drug, One Disease Paradigm of Pharmaceutical Innovation

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dc.contributor.authorGov, Esra
dc.contributor.authorGul, Aytac
dc.date.accessioned2026-02-27T07:33:11Z
dc.date.available2026-02-27T07:33:11Z
dc.date.issued2025
dc.description.abstractCancer is a disease with heterogenous molecular signatures that ought to be unpacked to achieve the overarching aim of precision oncology. A pan-cancer omics approach provides a systems science framework to explore shared and distinct mechanisms across cancers. We report here pan-cancer analyses of gene expression data from 17 cancers, for example, adrenocortical cancer, lung cancer, kidney cancer, and colorectal cancer, and 26 tissue types, using public datasets to construct disease-specific transcriptional networks. Using the hypergeometric test, 1005 microRNAs (miRNAs), 314 transcription factors (TFs), and 332 receptors were identified as regulatory molecules interacting with differentially expressed genes. Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed to explore their functional roles. Accordingly, we found miR-124-3p, miR-6799-5p, and miR-7106-5p as common miRNAs; Specificity Protein 1 (SP1), RELA Proto-Oncogene, NF-kappa B Subunit (RELA), and Nuclear Factor Kappa B Subunit 1 (NFKB1) as shared TFs; Cyclin-Dependent Kinase 2 (CDK2), Histone Deacetylase 1 (HDAC1), and ABL Proto-Oncogene 1, Non-Receptor Tyrosine Kinase (ABL1) as common receptors; and pathways in cancer, PI3K-Akt signaling, and p53 signaling as commonly enriched. Survival analysis in an independent dataset confirmed these findings: SP1 and NFKB1 were significant in 9 cancers, RELA in 6, whereas CDK2, HDAC1, and ABL1 were significant in 11, 10, and 10 cancers, respectively, out of the 17 cancers researched herein. In conclusion, these findings provide system-level insights on tumor heterogeneity and inform future cancer classification, for example, according to shared and distinct molecular signatures and development of therapies that might prove effective across several cancers. We underline that unpacking molecular signatures across multiple cancers also offers new prospects to move beyond the One Drug, One Disease paradigm of pharmaceutical innovation.
dc.description.sponsorshipHealth Institutes of Turkey(TUSEB) [2019-TA-01/3436]
dc.description.sponsorshipThis study was supported by the Health Institutes of Turkey(TUSEB) under project number 2019-TA-01/3436.
dc.identifier.doi10.1177/15578100251387873
dc.identifier.endpage573
dc.identifier.issn1536-2310
dc.identifier.issn1557-8100
dc.identifier.issue11
dc.identifier.pmid41111411
dc.identifier.startpage560
dc.identifier.urihttp://dx.doi.org/10.1177/15578100251387873
dc.identifier.urihttps://hdl.handle.net/20.500.14669/4480
dc.identifier.volume29
dc.identifier.wosWOS:001595926700001
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMary Ann Liebert, Inc
dc.relation.ispartofOMICS-A Journal of Integrative Biology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20260302
dc.subjectsystems biology
dc.subjectpharmaceutical innovation strategy
dc.subjectdrug development
dc.subjectpan-cancer
dc.subjectbiomarkers
dc.subjecttranscriptional regulatory network
dc.titlePan-Cancer Analyses of Shared and Distinct Gene Expression in 17 Cancers: Rethinking Cancer Classification and Moving Beyond One Drug, One Disease Paradigm of Pharmaceutical Innovation
dc.typeArticle

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