Department of Healthcare Biotechnology, Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan.
Research Service, Minneapolis VA Health Care System, Minneapolis, MN, USA.
Sci Rep. 2023 Aug 2;13(1):12504. doi: 10.1038/s41598-023-39804-0.
Hepatocellular carcinoma is a leading cause of cancer-related deaths due to its complexity in diagnosis, chemo-resistance, and aggressive nature. Identifying pathogenic single nucleotide polymorphism (SNP) in protein kinase C iota (PKCι) can be a potential biomarker in the prognosis and treatment of HCC. This study investigated the association between a SNP in PRKCI and the Pakistani population's hepatocellular carcinoma (HCC) risk. Obtained samples were first evaluated for ALT measurements and viral load quantification through reverse transcriptase-PCR. The PKCι nsSNP rs1199520604 was evaluated computationally by multiple consensus bioinformatics tools for predicting its potential deleterious effects. Its association with hepatitis C virus- (HCV) mediated HCC was then investigated through ARMS-PCR (Amplification Refractory Mutation System Polymerase Chain Reaction). SNP analysis of rs1199520604 was performed in 100 cases and 100 controls. Variant rs1199520604's homozygous T genotype is a risk factor allele for the HCV-induced HCC (odds ratio: 4.13, relative risk: 2.01, P-value < 0.0001). The heterozygous genotype is determined to protect HCV patients from HCC development (P < 0.001). The study highlighted the disease association of variant rs1199520604 with HCV-induced HCC in the Pakistani populations. This variant, after further validation through high-throughput investigation on a larger cohort, has the potential to be translated at the clinical level.
肝细胞癌是癌症相关死亡的主要原因，其诊断复杂、化疗耐药和侵袭性强。鉴定蛋白激酶 C iota (PKCι)中的致病单核苷酸多态性 (SNP) 可能是预测 HCC 预后和治疗的潜在生物标志物。本研究调查了 PRKCI 中的 SNP 与巴基斯坦人群肝细胞癌 (HCC) 风险之间的关联。首先通过逆转录-PCR 评估获得的样本的 ALT 测量值和病毒载量定量。通过多种共识生物信息学工具计算评估 PKCι nsSNP rs1199520604，预测其潜在的有害影响。然后通过 ARMS-PCR（扩增受阻突变系统聚合酶链反应）研究其与丙型肝炎病毒 (HCV) 介导的 HCC 的关联。对 rs1199520604 的 SNP 分析在 100 例病例和 100 例对照中进行。变体 rs1199520604 的纯合 T 基因型是 HCV 诱导的 HCC 的风险等位基因（比值比：4.13，相对风险：2.01，P 值 < 0.0001）。杂合基因型被确定为保护 HCV 患者免受 HCC 发展的影响（P < 0.001）。该研究强调了变体 rs1199520604 与巴基斯坦人群 HCV 诱导的 HCC 的疾病关联。该变体在更大的队列中通过高通量研究进一步验证后，有可能在临床水平转化。
