{ "abstract": "Background/Objectives: AP-2 transcription factors are increasingly recognized as key regulators in cancer biology. The TFAP2E gene, which encodes the AP-2ε transcription factor, remains understudied in cancer compared with other AP-2 family members. The scarcity of studies examining potential AP-2ε targets and related genes limits our understanding of its functional significance. Moreover, related studies have not incorporated a screening step to select the tumor type for justified molecular investigation. Through comparison of tumor–normal expression differences in a pan-cancer spectrum, this study prioritized ovarian serous carcinoma for downstream assessment. Methods: Expression patterns were evaluated using GENT2, GEPIA2, and TNMplot. After prioritizing ovarian serous carcinoma, TFAP2E and related signatures in TCGA-OV were analyzed using transcriptomic and clinical data from GDC and CDR, followed by comparison of findings with the GSE32062 cohort. The workflow included survival and clinicopathological analyses, outcome-independent limma-voom differential expression analysis and WGCNA, MCODE clustering, gene ontology, immune subtype and stemness assessment, PCA, CancerHallmarks enrichment, clinically adjusted Cox and competing-risk survival modeling, and HPA-derived immunostaining evaluation. Additional analyses assessed WGCNA parameter stability and preservation in GSE32062, an outcome-independent MAD-based variability screen, AP-2 family coexpression, and promoter motif enrichment. Results: TFAP2E was downregulated in ovarian cancer across the three queried resources, whereas higher expression was associated with favorable survival across multiple endpoints. Differential expression and WGCNA identified a TFAP2E-associated signature; its ontology indicated GPCR, stimulus responsiveness, and KRAS enrichment for the 933-gene module. The WGCNA pink module was stable across alternative settings, moderately preserved in GSE32062 (Zsummary = 7.86), and enriched in the outcome-independent MAD screening. GSE32062 supported concordant gene expression patterns and showed an association of TFAP2E with progression-free survival. Exploratory immune analyses showed a modestly increased proportion of C5 tumors in the higher-expression groups, whereas differences in stemness were statistically insignificant. The TFAP2E group associations with PFI and DSS in TCGA-OV and with PFS in GSE32062 remained significant after clinical adjustment; Fine-Gray sensitivity analyses gave consistent results for DSS. Immunohistochemistry provided protein-level characterization; eighteen entries differed between representative normal and tumor specimens, with lower tumor staining in fifteen. The seven-gene candidate set showed a clinically adjusted DSS association in TCGA-OV, which was not supported in the GSE32062 evaluation model. Conclusions: TFAP2E expression is associated with survival and a transcriptomic cross-cohort pattern in ovarian serous carcinoma. Covariate-adjusted and competing-risk analyses supported the association but did not establish clinical utility. The highlighted genes remain exploratory candidates for mechanistic investigation.", "abstract_shown": true, "affiliations": [ "Department of Functional Genomics, Medical University of Lodz, 90-752 Lodz, Poland", "Department of Molecular Biotechnology and Genetics, University of Lodz, 90-237 Lodz, Poland", "International Doctoral School, Medical University of Lodz, Hallera Square 1, 90-647 Lodz, Poland", "Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China", "Department of Nucleic Acid Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland" ], "article_type": "research article", "arxiv": null, "author_total": 10, "authors": [ { "affs": [ 0, 1 ], "name": "Damian Kołat", "orcid": "0000-0002-1086-3796" }, { "affs": [ 0, 2 ], "name": "Julia Gałęziewska", "orcid": "0009-0005-3377-4162" }, { "affs": [ 0 ], "name": "Paulina Buczek", "orcid": "0009-0000-0608-1794" }, { "affs": [ 3 ], "name": "Lin-Yong Zhao" }, { "affs": [ 0, 1 ], "name": "Mateusz Kciuk", "orcid": "0000-0002-8616-3825" }, { "affs": [ 0, 1 ], "name": "Żaneta Kałuzińska-Kołat", "orcid": "0000-0002-2335-3293" }, { "affs": [ 4 ], "name": "Małgorzata Kozłowska" }, { "affs": [ 4 ], "name": "Agnieszka Śliwińska", "orcid": "0000-0002-6864-0704" }, { "affs": [ 1 ], "name": "Renata Kontek", "orcid": "0000-0003-2859-9839" }, { "affs": [ 0 ], "name": "Elżbieta Płuciennik", "orcid": "0000-0002-6682-0402" } ], "bibtex": "https://research.draconitic.com/paper/96w5y91tfcyy0.bib", "cited_by": 0, "doi": "10.3390/cancers18193168", "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663952/?tool=EBI", "id": "96w5y91tfcyy0", "issns": [ "2072-6694" ], "landing_url": "https://europepmc.org/article/PMC/PMC13663952", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2743|Ovarian cancer diagnosis and treatment" ] ], "openalex": "W7215054516", "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663952/pdf/?tool=EBI", "pmcid": "PMC13663952", "pmid": null, "published": "2026-10-01", "publisher": "MDPI AG", "ris": "https://research.draconitic.com/paper/96w5y91tfcyy0.ris", "sources": [ { "first_seen": "2026-10-30T12:17:35Z", "native_id": "PMC:PMC13663952", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13663952" }, { "first_seen": "2026-10-30T12:19:58Z", "native_id": "10.3390/cancers18193168", "source": "crossref", "url": "https://www.mdpi.com/2072-6694/18/19/3168" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2743|Ovarian cancer diagnosis and treatment", "subfield": "reproductive-child" } ], "title": "TFAP2E Expression Is Associated with Survival and a Transcriptomic Pattern in Ovarian Serous Carcinoma, Supported by Hallmark and Protein-Level Characterization", "title_text": "TFAP2E Expression Is Associated with Survival and a Transcriptomic Pattern in Ovarian Serous Carcinoma, Supported by Hallmark and Protein-Level Characterization", "type": "peer-reviewed", "updated_at": "2026-10-30T12:19:58Z", "url": "https://research.draconitic.com/paper/96w5y91tfcyy0", "venue": "Cancers", "versions": [] }