{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:57:45Z","timestamp":1793113065513,"version":"4.5.0"},"reference-count":24,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia","award":["PNURSP2026R294"],"award-info":[{"award-number":["PNURSP2026R294"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: CDKN2A (p16^INK4a^) is integral to the regulation of the RB\u2013E2F cell-cycle checkpoint and is widely acknowledged as a surrogate marker for high-risk human papillomavirus (HPV)-related cervical neoplasia. Nevertheless, its diagnostic and prognostic significance in uterine corpus endometrial carcinoma (UCEC), a predominantly HPV-independent malignancy, remains inadequately characterized. This study utilized an integrated multi-omics approach to examine CDKN2A dysregulation in cervical squamous cell carcinoma (CESC) and UCEC. Methods: Pan-cancer and tumor\u2013normal differential expression analyses were performed using TIMER2.0 and GEPIA2 (TCGA\/GTEx). Clinicopathological correlations were assessed with UALCAN. Protein expression patterns were analyzed using immunohistochemistry data from the Human Protein Atlas (HPA). Prognostic significance and immune-infiltration associations were evaluated using TCGA survival data and TIMER modules. Independent transcriptomic validation and diagnostic classification performance were assessed using GEO datasets GSE9750 (CESC) and GSE63678 (UCEC), including ROC-AUC analysis with cross-validation. Results: Integrated analyses revealed elevated CDKN2A expression in both CESC and UCEC across multiple transcriptomic cohorts, with pronounced tumor-specific protein expression on immunohistochemistry. TCGA-only tumor\u2013normal RNA comparisons were non-significant, likely due to limited normal sample representation. In independent GEO cohorts, CDKN2A exhibited excellent tumor\u2013normal discrimination in CESC (AUC = 0.982) and moderate discrimination in UCEC (AUC = 0.761). Survival analysis indicated tumor-specific patterns, with limited prognostic stratification in CESC and context-dependent associations in UCEC. Immune-infiltration analysis suggested tumor-type-specific interactions between CDKN2A expression and immune cell subsets. Conclusions: CDKN2A exhibits strong diagnostic performance in HPV-associated cervical cancer and moderate, cohort-dependent discriminatory ability in endometrial carcinoma. These findings reinforce its established diagnostic role in CESC and propose adjunctive utility in UCEC, underscoring the importance of tumor-contextual interpretation of CDKN2A expression in gynecologic malignancies.<\/jats:p>","DOI":"10.3390\/genes17030281","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T15:52:38Z","timestamp":1772207558000},"page":"281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multi-Omics Analysis of CDKN2A (p16INK4a) in Cervical Carcinoma in the Context of Human Papillomavirus and in Endometrial Carcinoma"],"prefix":"10.3390","volume":"17","author":[{"given":"Rasha","family":"Elsayim","sequence":"first","affiliation":[{"name":"Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-9469","authenticated-orcid":false,"given":"Heba W.","family":"Alhamdi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Sciences, King Khalid University, P.O. Box 960, Abha 61413, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4996-7565","authenticated-orcid":false,"given":"Nihal","family":"Almuraikhi","sequence":"additional","affiliation":[{"name":"Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-616X","authenticated-orcid":false,"given":"Mariam Abdulaziz","family":"Alkhateeb","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taghreed Mohamed Osman","family":"Derar","sequence":"additional","affiliation":[{"name":"Health Sciences Department, College of Applied Studies, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami Habiballa Abdalla","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Health Sciences Department, College of Applied Studies, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8922-0143","authenticated-orcid":false,"given":"Esra\u2019a","family":"Abudouleh","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e197","DOI":"10.1016\/S2214-109X(22)00501-0","article-title":"Global estimates of incidence and mortality of cervical cancer in 2020: A baseline analysis of the WHO Global Cervical Cancer Elimination Initiative","volume":"11","author":"Singh","year":"2023","journal-title":"Lancet Glob. 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