High PAQR4 mRNA Expression May Play a Key Role in Prognosis of Kidney Renal Papillary Cell Carcinoma.

Objective: Kidney renal papillary cell carcinoma (KIRP) is the main subtype of renal cell carcinoma (RCC). The Progestin and AdipoQ Receptor Family Member 4 (PAQR4) has been found highly expressed in numerous cancers compared to normal tissues, but the role of PAQR4 in KIRP is unclear.

Methods: The expression levels of PAQR4 mRNA obtained from TCGA. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of PAQR4 expression in KIRP patients. Chi-square test was used to determine the correlation between clinical features and PAQR4 expression. Kaplan-Meier analysis and Cox analysis were used to determine the prognostic value of expression levels of PAQR4 in KIRP patients. Gene set enrichment analysis (GSEA) was also performed. The level of PAQR4 mRNA, protein expression and cell proliferation were analyzed through qRT-PCR, western blot and CCK-8 assay.

Results: The expression levels of PAQR4 was significantly higher in KIRP tissues. Highly expressed PAQR4 mRNA was correlated with gender, clinical stage and overall survival. Multivariate analysis indicated that PAQR4 was an independent risk factor for patients with KIRP. GPCR ligand binding, signaling by Rho GTPases, DNA repair and PI3K-AKT signaling pathway were associated with aberrant PAQR4 expressions. Moreover, the expression levels of PAQR4 was upregulated in human KIRP and the inhibition of PAQR4 reduced cells proliferation.

Conclusion: PAQR4 could be a potential diagnostic and prognostic biomarker in KIRP. The aberrant expression of this protein may trigger the alterations in the numerous signaling pathways, a process likely causing and accelerating the disease.