Pathogenicity of PKCγ Genetic Variants—Possible Function as a Non-Invasive Diagnostic Biomarker in Ovarian Cancer

Abstract

Ovarian cancer has the highest mortality rate among gynecologic malignancies, owing to its misdiagnosis or late diagnosis. Identification of its genetic determinants could improve disease outcomes. Conventional Protein Kinase C-γ (PKCγ) dysregulation is reported in several cancers. Similarly, its variant rs1331262028 is also reported to have an association with hepatocellular carcinoma. Therefore, the aim of the present study was to analyze the variant rs1331262028 association with ovarian cancer and to determine its impact on PKCγ’s protein interactions. Association of variation was determined through genotyping PCR (cohort size:100). Protein–protein docking and molecular dynamic simulation were carried out to study the variant impact of PKCγ interactions. The study outcome indicated the positive association of variant rs1331262028 with ovarian cancer and its clinicopathological features. Molecular dynamics simulation depicted the potential influence of variation on PKCγ molecular signaling. Hence, this study provided the foundations for assessing variant rs1331262028 as a potential prognostic marker for ovarian cancer. Through further validation, it can be applied at the clinical level.

Investigating pathogenic SNP of PKCι in HCV-induced hepatocellular carcinoma

“…Genomic DNA extraction and SNP analysis. The method used for Genomic DNA extraction was the phenol-chloroform method 8,18 . ARMS-PCR was performed to detect single nucleotide change in PRKCI.…”

“…SNPs in the genes GRIK1, MICA, HLA-DQA/DQB, and KIF1B have been reported to be associated with the risk of HCC 5 . The PKC family proteins have been positively associated with HCC in several studies 6 – 8 . However, those studies usually indicated its involvement in the carcinogenic process at a functional level.…”

The Role of NQO1 in Ovarian Cancer

“…Although NQO1 can protect normal cells from oxidative stress, it has been reported that a high expression of NQO1 at the early stages of carcinogenesis can favor cancer cell growth [4][5][6]. The clinical research is always focused on finding novel biomarkers for prognostic purposes as well as therapeutic targets since they are of crucial importance to improve the outcome of patients affected by aggressive neoplasms [7][8][9][10][11][12][13]. It has been reported that NQO1 is highly expressed in many solid tumors such as uterine cervix [14], endometrium [14], lung [15] colon [16], pancreas [17] and ovarian cancer [18].…”