Single-nucleotide polymorphisms in the coding region of a disintegrin and metalloproteinase with thrombospondin motifs 4 and hepatocellular carcinoma: A retrospective case-control study
Single-nucleotide polymorphisms in the coding region of a disintegrin and metalloproteinase with thrombospondin motifs 4 and hepatocellular carcinoma: A retrospective case-control study
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具有血小板反应蛋白基序 4 的解整合素和金属蛋白酶编码区的单核苷酸多态性与肝细胞癌：一项回顾性病例对照研究
DOI：
10.1002/cam4.2646
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发表时间：
2019-10-30
期刊：
影响因子：
4
通讯作者：
Long，Xi-Dai
中科院分区：
文献类型：
--
作者：
Wang，Xing-Zhizi;Tang，Wei-Zhong;Long，Xi-Dai
先前的研究表明，具有血小板反应蛋白1型基序4的解整合素和金属蛋白酶（ADAMTS4）的单核苷酸多态性（SNP）可能参与某些疾病的发病机制。然而，尚不清楚它们是否与肝细胞癌（HCC）相关。一项以医院为基础的病例对照研究，包括 862 例 HCC 病例和 1120 例对照，旨在评估 ADAMTS4 编码区的 258 个 SNP 对 HCC 风险和预后的影响。通过初步筛选分析，我们发现ADAMTS4中的6个SNP在病例和对照之间存在差异分布；然而，仅进一步鉴定了 rs538321148 和 rs1014509103 多态性来改变 HCC 风险（比值比：2.73 和 2.95；95% 置信区间，2.28‐3.29 和 2.43‐3.58；P 值，5.73 × 10−27 和分别为 1.36×10−27）。还观察到这两个 SNP 与乙型肝炎病毒和黄曲霉毒素 B1 的两种已知原因之间存在显着的相互作用。此外，rs538321148和rs1014509103多态性不仅与肿瘤的临床病理特征（如肿瘤分期和分级、微血管密度和血管转移）相关，而且与较差的总生存率相关。此外，这些 SNP 显着下调肿瘤组织中的 ADTMS4 表达。这些数据表明ADAMTS4编码区的SNP，例如rs538321148和rs1014509103，可能是预测HCC风险和预后的潜在生物标志物。
Previous studies have shown that single‐nucleotide polymorphisms (SNPs) of a disintegrin and metalloproteinase with thrombospondin type 1 motif 4 (ADAMTS4) may involve in the pathogenesis of some diseases. However, it is not clear whether they are associated with hepatocellular carcinoma (HCC). A hospital‐based case‐control study, including 862 cases with HCC and 1120 controls, was conducted to assess the effects of 258 SNPs in the coding regions ofADAMTS4on HCC risk and prognosis. We found that six SNPs inADAMTS4were differential distribution between cases and controls via the primary screening analyses; however, only rs538321148 and rs1014509103 polymorphisms were further identified to modify the risk of HCC (odds ratio: 2.73 and 2.95; 95% confidence interval, 2.28‐3.29 and 2.43‐3.58;P‐value, 5.73 × 10−27and 1.36 × 10−27, respectively). Significant interaction between these two SNPs and two known causes of hepatitis B virus and aflatoxin B1 were also observed. Furthermore, rs538321148 and rs1014509103 polymorphisms were associated not only with clinicopathological features of tumor such as tumor stage and grade, microvessel density, and vessel metastasis, but with poor overall survival. Additionally, these SNPs significantly downregulatedADATMS4expression in tumor tissues. These data suggest that SNPs in the coding region ofADAMTS4, such as rs538321148 and rs1014509103, may be potential biomarkers for predicting HCC risk and prognosis.