Abstract
Purpose: Although mutations are associated with carcinogenesis, little is known about survival-specific genes in clear cell renal cell carcinoma (ccRCC). We developed a customized next-generation sequencing (NGS) gene panel with 156 genes. The purpose of this study was to investigate whether the survival-specific genes we found were present in Korean ccRCC patients, and their association with clinicopathological findings. Materials and Methods: DNA was extracted from the formalin-fixed, paraffin-embedded tissue of 22 ccRCC patients. NGS was performed using our survival-specific gene panel with an Illumina MiSeq. We analyzed NGS data and the correlations between mutations and clinicopathological findings and also compared them with data from the Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) and Renal Cell Cancer-European Union (RECA-EU). Results: We found a total of 100 mutations in 37 of the 156 genes (23.7%) in 22 ccRCC patients. Of the 37 mutated genes, 11 were identified as clinicopathologically significant. Six were novel survival-specific genes (ADAMTS10, CARD6, NLRP2, OBSCN, SECISBP2L, and USP40), and five were top-ranked mutated genes (AKAP9, ARID1A, BAP1, KDM5C, and SETD2). Only CARD6 was validated as an overall survival-specific gene in this Korean study (p = 0.04, r = −0.441), TCGA-KIRC cohort (p = 0.0003), RECA-EU (p = 0.0005). The 10 remaining gene mutations were associated with clinicopathological findings; disease-free survival, mortality, nuclear grade, sarcomatoid component, N-stage, sex, and tumor size. Conclusions: We discovered 11 survival-specific genes in ccRCC using data from TCGA-KIRC, RECA-EU, and Korean patients. We are the first to find a correlation between CARD6 and overall survival in ccRCC. The 11 genes, including CARD6, NLRP2, OBSCN, and USP40, could be useful diagnostic, prognostic, and therapeutic markers in ccRCC.
Highlights
Clear cell renal cell carcinoma is one of the most lethal cancer types globally, accounting for 70–75% of all renal cancers [1]
Various studies are being conducted on genes related to survival in renal cell carcinoma (RCC), there are few survival-specific genes that can be used as biomarkers in clinical practice
We identified mutations in 22 Korean Clear cell renal cell carcinoma (ccRCC) patients using an next-generation sequencing (NGS) gene panel, which includes a total of 123 survival-specific genes discovered through machine learning with the Cancer Genome Atlas (TCGA)-KIRC data
Summary
Clear cell renal cell carcinoma (ccRCC) is one of the most lethal cancer types globally, accounting for 70–75% of all renal cancers [1]. In South Korea, ccRCC accounted for approximately 85% of all renal cell carcinoma (RCC) cases in 2015 [2]. Several studies on ccRCC-related mutant genes have been reported based on next-generation sequencing (NGS) techniques, but most of them were performed on a small scale [3]. The clinical, morphological, and genetic characteristics of RCC have been found to vary significantly from patient to patient due to high tumor heterogeneity [4]. It has been widely known that cancer is caused by the accumulation of cancer-causing gene mutations, and at least one protein-altering mutation is found in 85% of cancer tissues [5]. A diverse clinical picture arises due to the diversity of genetic mutations
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