<i>CCND1</i> and <i>PTEN</i> genes as markers of progression in vulvar cancer

Abstract

Purpose of the study. Studying the relative copy number of 12 genes: MYC, PTEN, CCND1, PIK3CA, TP53, CDKN2A, MDM2, MCL1, NFKBIA, MTAP, BIRC2, KMT2C, to search for potential prognostic cancer markers in vulvar cancer (VR).Patients and methods. The study included 50 patients aged 29–80 years with the diagnosis of squamous cell carcinoma of the vulva without metastases – group 1 (n = 25) and with metastases to the lymph nodes – group 2 (n = 25). Total DNA from paraffin blocks of tumor and conditionally healthy vulvar tissue served as the material for the study. The relative copy number of genes (RCQ) was assessed using the RT-qPCR method: MYC, PTEN, CCND1, PIK3CA, TP53, CDKN2A, MDM2, MCL1, NFKBIA, MTAP, BIRC2, KMT2C and referencegenes: GAPDH and B2M. Raw RT-qPCR data were analyzed using Bio-Rad CFX Manager software (ver. 2.1). RCQ of the genetic locus was calculated using the formula 2-ΔCt. Analysis of the significance of differences included determination of the OR (CI 95 %), Chi-square, Mann-Whitney U-test. Differences were considered statistically significant at p < 0.05.Results. Amplification was observed for 9 genes: MYC (48 % of cases), MCL1 (39 %), NFKBIA (46 %), CCND1 (52 %), PIK3CA (48 %), TP53 (62 %), MDM2 (40 %), BIRC2 (54 %), KMT2C (42 %); losses were recorded for 3 genes PTEN (44 % of cases), MTAP (32 %), CDKN2A (36 %). In the 2nd group of patients, a statistically significant 1.7-fold increase in RCQ of the CCND1 gene (p < 0.05) and a 1.9-fold decrease in RCQ of the PTEN gene (p < 0.05) were found.Conclusion. In the study, CCND1 amplification events and/or PTEN loss were associated with lymph node metastasis in RV patients. Thus, the copy numbers of these genes may serve as prognostic markers of the disease.