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.
Highlights
The second most common histological subtype of renal cell carcinomas (RCC) is the papillary RCC that accounts for 10–20 percent of all renal cancer cases [1]
After removing non-PRCC1/PRCC2 samples and Papillary renal cell carcinoma (PRCC) cases with mixed subtyping, a total of 138 PRCC1 and 135 PRCC2 samples were selected for further analysis (Figure 1A–1C)
Three main meta-analysis methods by combining p-value in MetaDE package were employed: 1) Maximum p-value, 2) Minimum p-value and 3) r-th ordered p-value (Figure 2B) [18]. 1758, 1558 and 1976 differentially expressed (DE) genes were detected by maximum P-value (maxP), minimum P-value (minP) and rth ordered P-value (roP) evaluation criteria, respectively, using detection competency curves and false discovery rate (FDR) cut-off less than 0.05 (Figure 2B, 2C and Table 3)
Summary
The second most common histological subtype of renal cell carcinomas (RCC) is the papillary RCC that accounts for 10–20 percent of all renal cancer cases [1]. Papillary renal cell carcinoma (PRCC) has two subtypes defined by different histological features. PRCC1 shows both papillae and tubular structures covered by small cells with scanty cytoplasm and small oval nuclei. PRCC2 indicates only papillary structures covered by large cells with abundant eosinophilic cytoplasm and large, spherical nuclei with prominent nucleoli [2]. PRCC2 is often a more aggressive disease that is associated with less differentiated histology phenotype, high number of nodal and distant metastases and worse survival rates comparing with PRCC1 [3,4]. Differential expression of components regulating cell-extracellular matrix (ECM) interactions has been implicated in PRCC1 [9]. How cell-ECM interactions are modulated in PRCC2 remains unknown
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