Proteomic Analysis of TCGA Data Reveals Limited Prognostic Value of p53 but Suggests BAX as a Potential Survival Marker in Cervical Carcinoma.

Cervical carcinoma is predominantly driven by high-risk human papillomavirus (HPV) infection, in which functional inactivation of p53 occurs mainly through viral oncoproteins rather than mutations in the TP53 gene. This raises questions concerning the prognostic relevance of TP53 gene status and p53 protein levels in this tumor type. This study aimed to systematically evaluate the prognostic significance of TP53 mutation status, p53 protein abundance, and selected downstream p53-regulated proteins in cervical carcinoma, with particular focus on tumors carrying wild-type TP53. Clinical and proteomic data from 162 cervical carcinoma patients were retrieved from The Cancer Genome Atlas (TCGA). Protein levels (p53, BAX, p21/CDKN1A, and TIGAR) were assessed using reverse-phase protein array (RPPA) data. Survival analyses were performed using Kaplan-Meier estimates with log-rank testing after stratification into quartile-based expression groups. The vast majority of tumors (~93%) harbored wild-type TP53, and the TP53 mutation status showed no association with patient survival. In tumors with wild-type TP53, p53 protein levels did not significantly correlate with overall survival, indicating a limited prognostic value. In contrast, elevated levels of the pro-apoptotic protein BAX showed a clear tendency to be associated with poorer overall and progression-free survival, suggesting BAX as a potential prognostic marker in this specific molecular context. The expression of p21/CDKN1A showed no prognostic relevance, while high TIGAR levels displayed a slight trend toward poorer survival, although without reaching statistical significance. In summary, in HPV-driven cervical carcinoma, neither the TP53 mutation status nor the p53 protein abundance reliably predict patient outcome. Instead, selected downstream effectors of p53 signaling-particularly BAX-may provide more informative prognostic insights in tumors retaining wild-type TP53. These findings highlight the importance of assessing functional outputs of p53 signaling rather than the p53 status alone in this disease context.