Molecular genetic approach for metastasis prediction in renal cancer patients

Abstract

Background. Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive of the histological subtypes of kidney cancer. It accounts for about 80 to 90% of all cases. The disease is asymptomatic up to the late stages, and it has a high mortality rate, especially when metastatic processes develop. About 30% of patients have distant metastases by the time the disease is detected.

The aim of this study was to develop a new, modern method for predicting the risk of metastases in patients with kidney cancer so as to optimize subsequent, personalized treatment.

Methods. Based on clinical and pathomorphological data, paired samples of tumor and normal tissue were selected for advanced molecular genetic study. RNA and DNA were isolated by standard methods. Gene expression was analyzed using TaqMan® Gene Expression Assays (Applied Biosystems, USA). The degree of gene methylation was assessed using bisulfite conversion of DNA and quantitative methylation-specific real-time PCR (MS-PCR). Statistical analysis was performed with Statistica 10.0 software.

Results. Decreased expression of the protein-coding genes CA9, NDUF4L2, EGLN3, and BHLHE41 was associated with the development of metastases during the first-year follow-up (p<0.05, ROC analysis). In addition, increased methylation levels of MIR125B-1, MIR193A, MIR1258, MIR34B/C genes were associated with metastasis (p < 0.002, ROC-analysis). Based on these findings, a new panel of genes was created for predicting the risk of metastases in patients with kidney cancer.

Conclusion. A newly proposed gene panel allows identification with high sensitivity and specificity patients whose tumor has metastatic potential. With a negative test, there is an 83% chance that there are no metastases.