Abstract
BackgroundWith the advent of second-generation sequencing, the expression of gene transcripts can be digitally measured with high accuracy. The purpose of this study was to systematically profile the expression of both mRNA and miRNA genes in clear cell renal cell carcinoma (ccRCC) using massively parallel sequencing technology.MethodologyThe expression of mRNAs and miRNAs were analyzed in tumor tissues and matched normal adjacent tissues obtained from 10 ccRCC patients without distant metastases. In a prevalence screen, some of the most interesting results were validated in a large cohort of ccRCC patients.Principal FindingsA total of 404 miRNAs and 9,799 mRNAs were detected to be differentially expressed in the 10 ccRCC patients. We also identified 56 novel miRNA candidates in at least two samples. In addition to confirming that canonical cancer genes and miRNAs (including VEGFA, DUSP9 and ERBB4; miR-210, miR-184 and miR-206) play pivotal roles in ccRCC development, promising novel candidates (such as PNCK and miR-122) without previous annotation in ccRCC carcinogenesis were also discovered in this study. Pathways controlling cell fates (e.g., cell cycle and apoptosis pathways) and cell communication (e.g., focal adhesion and ECM-receptor interaction) were found to be significantly more likely to be disrupted in ccRCC. Additionally, the results of the prevalence screen revealed that the expression of a miRNA gene cluster located on Xq27.3 was consistently downregulated in at least 76.7% of ∼50 ccRCC patients.ConclusionsOur study provided a two-dimensional map of the mRNA and miRNA expression profiles of ccRCC using deep sequencing technology. Our results indicate that the phenotypic status of ccRCC is characterized by a loss of normal renal function, downregulation of metabolic genes, and upregulation of many signal transduction genes in key pathways. Furthermore, it can be concluded that downregulation of miRNA genes clustered on Xq27.3 is associated with ccRCC.
Highlights
As the most common type of kidney cancer in adults, renal cell carcinoma (RCC) is responsible for approximately 90% of all cases [1]
Our results indicate that the phenotypic status of clear cell renal cell carcinoma (ccRCC) is characterized by a loss of normal renal function, downregulation of metabolic genes, and upregulation of many signal transduction genes in key pathways
It can be concluded that downregulation of miRNA genes clustered on Xq27.3 is associated with ccRCC
Summary
As the most common type of kidney cancer in adults, renal cell carcinoma (RCC) is responsible for approximately 90% of all cases [1]. Despite the high incidence of this type of malignancy in populations of different ethnicities throughout the world, the precise pathogenic mechanisms underlying ccRCC have not been clearly elucidated. Environmental factors, such as cigarette smoking, have been suggested to be associated with increased susceptibility for renal cancer in over 35% of male patients [5], other risk factors include obesity, hypertension, and acquired cystic kidney disease is associated with end-stage renal disease [6]. The purpose of this study was to systematically profile the expression of both mRNA and miRNA genes in clear cell renal cell carcinoma (ccRCC) using massively parallel sequencing technology
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