Meta-analysis of gene expression and integrin-associated signaling pathways in papillary renal cell carcinoma subtypes

Abstract

Papillary renal cell carcinoma (PRCC) is the second most common renal cell carcinoma (RCC) that can be further subdivided into type 1 (PRCC1) and type 2 (PRCC2) RCCs based on histological and genetic features. PRCC2 is often more aggressive than PRCC1. While integrin-associated protein complexes mediate tumorigenesis and metastases in many types of cancers it is not known whether integrin-mediated signaling impacts PRCC and differs between PRCC1 and PRCC2. In this study, we combined the analysis of five PRCC gene expression datasets derived from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) by using integrative bioinformatics pipelines. We found 1475 differentially expressed genes among which 37 genes were associated with integrin pathways. In comparison with PRCC1, PRCC2 cases showed upregulated expression of α5-integrin (ITGA5) whereas the expression of α6- (ITGA6) and β8-integrins (ITGB8) was downregulated. Because PRCC2 occurs more frequently in men, the meta-analysis was extended to explore the gender effects. This analysis revealed 8 genes but none of them was related to integrin pathways suggesting that other mechanisms than integrin-mediated signaling underlie the observed gender differences in the pathogenicity of PRCC2.