Abstract
We aimed to identify and investigate genes that are essential for the development of clear cell renal cell carcinoma (ccRCC) and sought to shed light on the mechanisms of its progression and create prognostic markers for the disease. We used real-time PCR to study the expression of 20 genes that were preliminarily selected based on their differential expression in ccRCC, in 68 paired tumor/normal samples. Upon ccRCC progression, seven genes that showed an initial increase in expression showed decreased expression. The genes whose expression levels did not significantly change during progression were associated mainly with metabolic and inflammatory processes. The first group included CA9, NDUFA4L2, EGLN3, BHLHE41, VWF, IGFBP3, and ANGPTL4, whose expression levels were coordinately decreased during tumor progression. This expression coordination and gene function is related to the needs of tumor development at different stages. Specifically, the high correlation coefficient of EGLN3 and NDUFA4L2 expression may indicate the importance of the coordinated regulation of glycolysis and mitochondrial metabolism. A panel of CA9, EGLN3, BHLHE41, and VWF enabled the prediction of survival for more than 3.5 years in patients with ccRCC, with a probability close to 90%. Therefore, a coordinated change in the expression of a gene group during ccRCC progression was detected, and a new panel of markers for individual survival prognosis was identified.
Highlights
Clear cell renal cell carcinoma is the most common type of kidney neoplasm
The stage I/II Clear cell renal cell carcinoma (ccRCC) samples showed an increase in the expression of CA9, NDUFA4L2, HIG2, INHBB, IGFBP3, ANGPTL4, EGLN3, VWF, TYROBP, BHLHE41, STC2, NNMT, SLC16A3, C1QA, and CD36 relative to normal kidney tissue
The expression of seven genes was significantly lower in stage IV relative to stages I/II; i.e., CA9, NDUFA4L2, EGLN3, BHLHE41, VWF, IGFBP3, and ANGPTL4 (p = 0.001–0.027) (Table 2)
Summary
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney neoplasm. It accounts for 80–90% of kidney cancer worldwide. ccRCC is characterized by high malignancy and results in the highest mortality rate among the genitourinary system cancers [1].Despite the annual increase in the incidence of kidney cancer, the development of early detection technologies has reduced the mortality rate due to this disease in recent decades [2]. Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney neoplasm. It accounts for 80–90% of kidney cancer worldwide. CcRCC is characterized by high malignancy and results in the highest mortality rate among the genitourinary system cancers [1]. Despite the annual increase in the incidence of kidney cancer, the development of early detection technologies has reduced the mortality rate due to this disease in recent decades [2]. The existing and applied prognostic systems that are based on histological and clinical parameters are not accurate enough to reliably detect risk [4,5,6,7,8]. There is a need to develop new forecasting methods and biomarkers for detecting ccRCC
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