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Peer-reviewedCC BYCancers

TFAP2E Expression Is Associated with Survival and a Transcriptomic Pattern in Ovarian Serous Carcinoma, Supported by Hallmark and Protein-Level Characterization

  • Damian Kołat1,2
  • Julia Gałęziewska1,3
  • Paulina Buczek1
  • Lin-Yong Zhao4
  • Mateusz Kciuk1,2
  • Żaneta Kałuzińska-Kołat1,2
  • Małgorzata Kozłowska5
  • Agnieszka Śliwińska5
  • Renata Kontek2
  • Elżbieta Płuciennik1
5 affiliations
  1. 1Department of Functional Genomics, Medical University of Lodz, 90-752 Lodz, Poland
  2. 2Department of Molecular Biotechnology and Genetics, University of Lodz, 90-237 Lodz, Poland
  3. 3International Doctoral School, Medical University of Lodz, Hallera Square 1, 90-647 Lodz, Poland
  4. 4Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
  5. 5Department of Nucleic Acid Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland
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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.

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Cite

BibTeXRIS
BibTeX
@article{kolat2026tfap2e,
  title = {{TFAP2E Expression Is Associated with Survival and a Transcriptomic Pattern in Ovarian Serous Carcinoma, Supported by Hallmark and Protein-Level Characterization}},
  author = {Damian Kołat and Julia Gałęziewska and Paulina Buczek and Lin-Yong Zhao and Mateusz Kciuk and Żaneta Kałuzińska-Kołat and Małgorzata Kozłowska and Agnieszka Śliwińska and Renata Kontek and Elżbieta Płuciennik},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18193168},
  url = {https://europepmc.org/article/PMC/PMC13663952},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - TFAP2E Expression Is Associated with Survival and a Transcriptomic Pattern in Ovarian Serous Carcinoma, Supported by Hallmark and Protein-Level Characterization
AU  - Damian Kołat
AU  - Julia Gałęziewska
AU  - Paulina Buczek
AU  - Lin-Yong Zhao
AU  - Mateusz Kciuk
AU  - Żaneta Kałuzińska-Kołat
AU  - Małgorzata Kozłowska
AU  - Agnieszka Śliwińska
AU  - Renata Kontek
AU  - Elżbieta Płuciennik
PY  - 2026
DA  - 2026/10/01
JO  - Cancers
DO  - 10.3390/cancers18193168
UR  - https://europepmc.org/article/PMC/PMC13663952
AB  - 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.
SN  - 2072-6694
ER  -