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Gene expression profiling of clear cell renal cell carcinoma with sarcomatoid transformation

ABSTRACT: Renal cell carcinoma (RCC) with sarcomatoid transformation features a biphasic tumour with both sarcomatoid and carcinomatous components. Clear cell RCC (ccRCC) is the most common RCC subtype, frequently exhibits sarcomatoid transformation. The pathogenesis of sarcomatoid ccRCC remains unclear. This study aimed to identify the genes and pathways involved in sarcomatoid ccRCC using gene expression profiling. We analysed three distinct regions including sarcomatoid component, clear cell component and matched normal kidney tissue from formalin-fixed, paraffin-embedded (FFPE) tissue samples of four patients. RNA was extracted and gene expression profiles were analysed using the NanoString nCounter® PanCancer Pathways Panel on the NanoString nCounter® Analysis System. Data analysis was performed using NanoString nSolver™ Analysis Software. Significant gene expression differences were defined with a threshold of fold change ˃ 4 and P-value ˂ 0.05. Compared to normal kidney tissue, 17 genes were significantly different in the clear cell component, with 5 were upregulated and 12 downregulated. The most significantly upregulated and downregulated genes were GDF6 and SFRP1 respectively. In the sarcomatoid component, 85 genes showed differences, with 38 upregulated and 47 downregulated. COL11A1 and LRP2 were the most significantly overexpressed and underexpressed genes respectively. When comparing sarcomatoid component with clear cell component, there were 53 significantly dysregulated genes, including epithelial-mesenchymal transition markers such as MMP9 and FN1. Pathway analysis indicated that PI3K was the most frequently deregulated pathway in the sarcomatoid component, suggesting its role in sarcomatoid transformation. This study provides insights into the gene expression patterns in ccRCC with sarcomatoid transformation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE285848 | GEO | 2025/01/21

REPOSITORIES: GEO

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Project description:Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Currently, there are no biomarkers for the diagnostic, prognostic, or predictive applications in RCC. MicroRNAs (miRNAs) are short non protein-coding RNAs that negatively regulate gene expression and have been shown to be involved in cancer. We analyzed a total of 70 matched pairs of clear cell RCC (ccRCC) and normal kidney tissues from the same patients by microarray analysis and validated our results by quantitative real time PCR. We identified 166 miRNAs significantly dysregulated in ccRCC. MiR-122, miR-155 and miR-210 had the highest fold changes of overexpression while miR-200c, miR-335, and miR-218 were the most downregulated. We performed extensive bioinformatics analysis including a combinatorial analysis of previously reported miRNAs dysregulated in RCC and extensive target prediction analysis. Many miRNAs were predicted to target a number of genes involved in RCC pathogenesis. Our results showed that miRNA dysregulation in RCC can be attributed in part, to chromosomal aberrations, the co-regulation of miRNA clusters, and co-expression with host genes. We also correlated miRNA expression with clinical characteristics and found miR-155 expression was correlated with ccRCC tumor size. In conclusion, our analysis showed that a number of miRNAs are dysregulated in ccRCC and may contribute to kidney cancer pathogenesis by targeting more than one key molecule. We identified mechanisms that may contribute to miRNA dysregulation in ccRCC. Dysregulated miRNAs represent potential biomarkers for kidney cancer. We preformed a miRNA microarray on 20 pairs of matched primary clear cell renal cell carcinoma (ccRCC) and normal kidney tissue from the same patient (St. Michael's Hospital, Toronto, Canada). One matched pair was used per array for a total of 20 arrays. Microarray results were validated by quantitative real time PCR using an independent set of 50 matched pairs of ccRCC and normal kidney tissue from the same patient.

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Gene expression profiling of clear cell renal cell carcinoma with sarcomatoid transformation

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