Association of Parkin with P53 expression and their prognostic significance in north Indian colorectal cancer patients

Abstract

PurposeGenetic and epigenetic alterations of Parkin (PRKN gene) have been identified in colorectal cancer (CRC), but its correlation with P53 (TP53 gene) status and progression of CRC is not well established. This study investigates the association of Parkin expression with P53, clinical features, and prognosis in the north Indian population. MethodsImmunohistochemical expressions of Parkin and P53 were evaluated in 322 paired samples of colorectal tumor and corresponding non-tumor. They were correlated with pathologic parameters to evaluate their prognostic importance. Kaplan-Meier survival and Cox regression analyses were executed to evaluate factors contributing to the survival of colorectal cancer. In addition, the cancer genome atlas (TCGA) database was used to analyse Parkin and P53 status using cBioPortal and UALCAN. ResultOur data revealed a significant relationship of Parkin loss with different staining patterns of P53. Parkin and P53 expressions were significantly correlated with tumor aggressiveness and metastasis; also confirmed by TCGA data. Parkin negative expression was associated with shorter overall survival (OS), while in the case of P53, scattered nuclear expression showed better OS than the other staining patterns. The multivariate analysis revealed Parkin expression and lymph node metastasis are independent prognostic factors for shorter overall survival. ConclusionOur results provide the first evidence of a correlation between Parkin and different staining patterns of P53. Parkin expression is correlated with malignant attributes and is a strong independent predictor of adverse clinical outcomes in north Indian CRC patients and may serve as a potential biomarker to assess the risk of CRC and its therapy.