High CENPA expression in papillary renal cell carcinoma tissues is associated with poor prognosis

Abstract

Objective: This work focused on investigating the relation of centromeric protein A (CENPA) gene expression with prognosis of papillary renal cell carcinoma (PRCC). Methods: We obtained data from PRCC cases in TCGA. Thereafter, CENPA levels between the paired PRCC and matched non-carcinoma samples were analyzed by Wilcoxon rank-and-sum test, while the relations of clinicopathological characteristics with CENPA level were examined by logistic regression and Wilcoxon rank-sum test. The prognostic value of CENPA was assessed by plotting the receiver operating feature curve (ROC) and calculating the value of area under curve (AUC). In addition, relations between clinicopathological features and PRCC survival were analyzed through Kaplan-Meier (KM) and Cox regression analyses. Additionally, we constructed a nomogram according to multivariate Cox regression results for predicting how CENPA affected patient survival. We also determined CENPA levels within cancer and matched non-carcinoma samples through immunohistochemistry (IHC). Finally, we utilized functional enrichment for identifying key pathways related to differentially expressed genes (DEGs) between PRCC cases with CENPA up-regulation and down-regulation. Results: CENPA expression enhanced in PRCC tissues compared with healthy counterparts (P <0.001). CENPA up-regulation was related to clinical stage and pathological TNM stage (P<0.05). Meanwhile, the ROC curve indicated that CENPA had a remarkable diagnostic capacity for PRCC (AUC=0.936). As revealed by KM curve, PRCC cases with CENPA up-regulation were associated with poor survival compared with those with CENPA down-regulation (risk ratio, RR=3.07, 95% CI: 1.58-5.97, P=0.001). In the meantime, univariate as well as multivariate analysis showed an independent association of CENPA with overall survival (OS, P <0.001). IHC analysis indicated that PRCC cases showed an increased CENPA positive rate compared with controls. As revealed by functional annotations, CENPA was enriched into pathways associated with KEGG - NEUROACTIVE - LIGAND - RECEPTOR - INTERACTION, KEGG - CYTOKINE - CYTOKINE - RECEPTOR INTERACTION, NABA - ECM - REGULATORS, NABA - ECM - GLYCOPROTEINS, and NABA - CORE - MATRISOME pathways. Conclusion: CENPA expression increases within PRCC samples, which predicts dismal PRCC survival. CENPA may become a molecular prognostic marker and therapeutic target for PRCC patients.