Prediction of Distant Metastases in Patients with Kidney Cancer Based on Gene Expression and Methylation Analysis

Natalya Apanovich; Alexey Matveev; Natalia Ivanova; Alexey Burdennyy; Pavel Apanovich; Irina Pronina; Elena Filippova; Tatiana Kazubskaya; Vitaly Loginov; Eleonora Braga; Andrei Alimov

doi:10.3390/diagnostics13132289

Prediction of Distant Metastases in Patients with Kidney Cancer Based on Gene Expression and Methylation Analysis

Diagnostics (Basel). 2023 Jul 6;13(13):2289. doi: 10.3390/diagnostics13132289.

Authors

Affiliations

¹ Research Centre for Medical Genetics, 1 Moskvorechye St., Moscow 115522, Russia.
² Federal State Budgetary Institution (N.N. Blokhin National Medical Research Center of Oncology) of the Ministry of Health of the Russian Federation, 24 Kashirskoe Shosse, Moscow 115478, Russia.
³ Institute of General Pathology and Pathophysiology, Baltijskaya St. 8, Moscow 125315, Russia.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive histological type of cancer in this location. Distant metastases are present in approximately 30% of patients at the time of first examination. Therefore, the ability to predict the occurrence of metastases in patients at early stages of the disease is an urgent task aimed at personalized treatment. Samples of tumor and paired histologically normal kidney tissue from patients with metastatic and non-metastatic ccRCC were studied. Gene expression was analyzed using real-time PCR. The level of gene methylation was evaluated using bisulfite conversion followed by quantitative methylation-specific PCR. Two groups of genes were analyzed in this study. The first group includes genes whose expression is significantly reduced during metastasis: CA9, NDUFA4L2, EGLN3, and BHLHE41 (p < 0.001, ROC analysis). The second group includes microRNA genes: MIR125B-1, MIR137, MIR375, MIR193A, and MIR34B/C, whose increased methylation levels are associated with the development of distant metastases (p = 0.002 to <0.001, ROC analysis). Based on the data obtained, a combined panel of genes was formed to identify patients whose tumors have a high metastatic potential. The panel can estimate the probability of metastasis with an accuracy of up to 92%.

Keywords: CpG methylation; clear cell renal cell carcinoma; differential gene expression; metastasis.

Grants and funding

This research was carried out within the state assignment of the Ministry of Science and Higher Education of the Russian Federation for Research Centre for Medical Genetics and for the Institute of General Pathology and Pathophysiology (state task NFGFU-2022-0007).