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基质金属蛋白酶-11 基因多态性与埃及患者肝癌发展的风险。

Matrix Metalloproteinase-11 Gene Polymorphisms as a Risk for Hepatocellular Carcinoma Development in Egyptian Patients.

机构信息

Biochemistry Division, Department of Chemistry, Faculty of Science, Menoufia University, Shebein El-Kom, Egypt.

Departement of Clinical Pathology, National Liver Institute, Menoufia University, Shebein El-Kom, Egypt.

出版信息

Asian Pac J Cancer Prev. 2020 Dec 1;21(12):3725-3734. doi: 10.31557/APJCP.2020.21.12.3725.

Abstract

BACKGROUND

Chronic hepatitis C (CHC) virus infection is one of major risk factors of hepatocellular carcinoma (HCC) in Egypt, which is a major cause of cancer mortalityin the world. Matrix metalloproteinase-11 (MMP-11) has an important role in tumor migration and metastasis. Therefore, this study aimed to determine relation between MMP-11 gene polymorphisms and risk of HCC development among Egyptian cirrhotic patients.

SUBJECTS AND METHODS

Two hundred and sixty patients were included, 140 of them with HCC on top of CHC and 120 patients with post CHC liver cirrhosis (LC) as well as 140 subjects were enrolled in the study as healthy controls. Two single nucleotide polymorphisms (SNPs) rs738791 and rs738792 for MMP-11 gene were done using real-time PCR.

RESULTS

Combination of CT and TT allele of rs738791 genotypes was more significantly frequent in HCC compared to LC patients and controls, however, a higher frequency of T allele was found in HCC patients compared to LC and controls. In spite of lake of significant difference between patient groups regarding the rs738792 genotypes, the CC genotype was considered a risk of developing portal vein thrombosis, and was associated with advanced tumor stage, increased tumor size, higher Cancer of the Liver Italian Program [CLIP] score, more advanced Barcelona stage [D] and with child Pugh class [C].

CONCLUSION

Genetic variations in MMP-11 may be implicated in post HCV-HCC development and might be dependable biomarkers for HCC progression.

摘要

背景

慢性丙型肝炎(CHC)病毒感染是埃及肝细胞癌(HCC)的主要危险因素之一,这是全球癌症死亡的主要原因。基质金属蛋白酶-11(MMP-11)在肿瘤迁移和转移中具有重要作用。因此,本研究旨在确定 MMP-11 基因多态性与埃及肝硬化患者 HCC 发展风险之间的关系。

受试者和方法

纳入了 260 名患者,其中 140 名患有 CHC 基础上的 HCC,120 名患有 CHC 后肝硬化(LC),140 名作为健康对照者纳入研究。使用实时 PCR 检测 MMP-11 基因的两个单核苷酸多态性(SNP)rs738791 和 rs738792。

结果

与 LC 患者和对照组相比,rs738791 基因型的 CT 和 TT 等位基因组合在 HCC 中更为频繁,但 HCC 患者的 T 等位基因频率高于 LC 和对照组。尽管患者组之间 rs738792 基因型无显著差异,但 CC 基因型被认为是发生门静脉血栓形成的风险因素,与晚期肿瘤分期、肿瘤增大、更高的癌症意大利计划 [CLIP] 评分、更晚期的巴塞罗那分期 [D] 和 Child-Pugh 分类 [C] 相关。

结论

MMP-11 的遗传变异可能与 HCV-HCC 后发展有关,可能是 HCC 进展的可靠生物标志物。

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