肝细胞肝癌是导致癌症相关死亡的主要原因，由于其在诊断、化疗耐药性和侵袭性方面的复杂性。鉴定蛋白激酶C-ι（PKCι）中致病性单核苷酸多态性（SNP）可能成为肝细胞癌（HCC）预后和治疗的潜在生物标志物。本研究探讨了PRKCI中SNP与巴基斯坦人群肝细胞癌（HCC）风险之间的关联。首先对获取的样本通过反转录聚合酶链反应进行丙氨酸氨基转移酶（ALT）测量和病毒载量定量进行评估。然后，通过多个共识生物信息学工具计算评估PKCι非同义SNP rs1199520604及其潜在有害效应。随后通过Amplification Refractory Mutation System Polymerase Chain Reaction（ARMS-PCR）对其与丙型肝炎病毒（HCV）介导的HCC之间的关联进行了研究。在100例病例和100例对照中进行了rs1199520604的SNP分析。变异的rs1199520604的纯合子T基因型是HCV引起的HCC的风险基因位点（比值比：4.13，相对风险：2.01，P值＜0.0001）。杂合子基因型被确定为保护HCV患者不发展为HCC（P＜0.001）。该研究凸显了rs1199520604变异体与巴基斯坦人群中HCV引起的HCC的疾病关联。该变异体，在更大队列上通过高通量研究进一步验证后，有潜力在临床层面进行转化。© 2023. 作者。

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.© 2023. The Author(s).