Purpose: Activation of actin cytoskeleton remodeling is an important stage preceding cancer cell metastasis. Previous genome-wide association studies (GWAS) have identified multiple hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)-associated risk loci. However, limited sample size or strict significance threshold of GWAS may cause HBV-related HCC risk-associated genetic loci to be undetected. We aimed to investigate the performance of the SNP rs13025377 in PPP1CB in HCC.
Patients and Methods: We performed a case–control study including 1161 cases and 1353 controls to evaluate associations between single nucleotide polymorphisms (SNPs) from 98 actin-cytoskeleton regulatory genes and risk of HBV-related HCC. The effects of SNPs on HBV-related HCC risk were assessed under logistic regression model and corrected by false discovery rate (FDR).
Results: We found that rs13025377 in PPP1CB was significantly associated with HBV-related HCC risk [odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.72∼ 0.91, P = 4.88× 10^{– 4}]. The risk allele A of rs13025377 increased PPP1CB expression levels in normal liver tissue. SNP rs4665434 was tagged by rs13025377 (r² = 0.9) and its protective allele disrupted CTCF and Cohesin motifs. According to public datasets, PPP1CB, CTCF and Cohesin expression levels are increased in tumor tissues. Kaplan–Meier plots demonstrated that higher PPP1CB expression was significantly associated with shorter overall survival (OS). Moreover, we observed strong correlation between CTCF, Cohesin, and PPP1CB in various liver tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis confirmed that PPP1CB plays a role in HCC through actin-cytoskeleton regulation.
Conclusion: Thus, these findings indicated that PPP1CB may be a key gene in actin-cytoskeleton regulation and rs13025377 contributes to the risk of HBV-related HCC by regulating PPP1CB expression.

Keywords: genome-wide association studies, PPP1CB, CTCF, cohesin, SNP, HBV-related hepatocellular carcinoma


中文翻译：

---

PPP1CB的遗传变异影响汉族乙型肝炎病毒相关肝细胞癌的风险：基于通路的分析

目的：激活肌动蛋白细胞骨架重塑是癌细胞转移前的一个重要阶段。以前的全基因组关联研究 (GWAS) 已经确定了多个与乙型肝炎病毒 (HBV) 相关的肝细胞癌 (HCC) 相关的风险基因座。然而，有限的样本量或 GWAS 严格的显着性阈值可能导致 HBV 相关的 HCC 风险相关基因位点未被检测到。我们旨在研究 HCC 中PPP1CB中 SNP rs13025377 的性能。
患者和方法：我们进行了一项病例对照研究，包括 1161 例病例和 1353 例对照，以评估来自 98 个肌动蛋白细胞骨架调节基因的单核苷酸多态性 (SNP) 与 HBV 相关 HCC 风险之间的关联。在逻辑回归模型下评估 SNP 对 HBV 相关 HCC 风险的影响，并通过错误发现率 (FDR) 进行校正。
结果：我们发现 PPP1CB 中的rs13025377与 HBV 相关的 HCC 风险显着相关[优势比 (OR) = 0.81, 95% 置信区间 (CI) = 0.72∼0.91, P = 4.88× 10 ^{– 4} ]。rs13025377的风险等位基因A增加了正常肝组织中PPP1CB的表达水平。SNP rs4665434 被 rs13025377 (r ² = 0.9) 标记，其保护性等位基因被破坏CTCF和Cohesin基序。根据公共数据集，肿瘤组织中PPP1CB、CTCF和Cohesin的表达水平增加。Kaplan-Meier 图表明，较高的PPP1CB表达与较短的总生存期 (OS) 显着相关。此外，我们观察到各种肝组织中CTCF、Cohesin和PPP1CB之间的强相关性。京都基因和基因组百科全书 (KEGG) 富集分析证实PPP1CB通过肌动蛋白-细胞骨架调控在 HCC 中发挥作用。
结论：因此，这些发现表明PPP1CB可能是肌动蛋白-细胞骨架调控的关键基因，rs13025377 通过调节PPP1CB表达增加了 HBV 相关 HCC 的风险。

关键词：全基因组关联研究，PPP1CB，CTCF，cohesin，SNP，HBV相关肝细胞癌