Gene expression profile of cancerous and non-cancerous renal tissues

ABSTRACT: Clear cell renal cell carcinoma (ccRCC), is the most common subtype of kidney tumors and characterised by the highest mortality rates among the genitourinary cancers. The currently used models for predicting patient outcome, are based on clinicopathological features only, however patients with similar measures can still have divergent outcomes. This study aimed at identification of novel prognostic DNA methylation biomarkers to aid in predicting patient survival. As DNA methylation in the most cases is related to alteration of gene expression, firstly, SurePrint G3 Human GE 8×60K Microarrays were used for gene expression profiling in 4 ccRCC tissues and paired non-cancerous renal tissue (NRT) samples. The DNA methylation status of four down-regulated genes were evaluated in 123 ccRCC and 45 NRT samples by means of methylation specific PCR (MSP). Microarray-based transcriptome comparison of 4 ccRCC and 4 NRT samples identified 3942 genes, that were significantly deregulated (P < 0.050) with absolute fold change (FC) value of ≥2. A half of these genes (N = 1958) were down-regulated and four of such genes with moderate-to-high alteration were selected for the further DNA methylation analysis. DNA hypermethylation of all selected genes were cancer specific (P<0.050) with the frequency in tumour tissues ranging from 18 to 42%. The methylated status of at lest one gene showed significant associations with larger tumor size, higher Fuhrman and WHO/ISUP grades as well as the presence of tumor intravascular invasion and necrosis. Moreover, the methylated status of the panel of tree genes was highly predictive for poorer overall survival and outperformed the prognostic value of tumor stage and tumor necrosis. In conclusion, the three-gene DNA methylation biomarker panel predicts outcome of patients with ccRCC and might be used to improve current prognostic models.

ORGANISM(S): Homo sapiens

PROVIDER: GSE168845 | GEO | 2021/03/14

REPOSITORIES: GEO