Division of Gastroenterology, Department of Internal Medicine, Necmettin Erbakan University, Meram School of Medicine, Meram, Konya, Turkey.
Division of Gastroenterology, Department of Internal Medicine, Van Training and Research Hospital, Van, Turkey.
Turk J Gastroenterol. 2021 Jul;32(7):593-599. doi: 10.5152/tjg.2021.20657.
Hepatocellular carcinoma (HCC) is one of the important causes of mortality due to malignancy. Toll-like receptors (TLRs) are very important in liver pathophysiology in terms of their roles in the innate immune system, such as the regulation of inflammation, wound healing, stimulation of adaptive immune responses, promotion of epithelial regeneration, and carcinogenesis. In this study, we planned to examine the role of TLR1 (rs4833095, rs5743551) and nucleotide-binding oligomerization domain (NOD2) (rs2066844, rs2066845, rs2066847) polymorphisms in the development of HCC and their effects on the clinical presentation of HCC patients.
Our study was designed prospectively. Cirrhotic and HCC patients who were followed up in our clinic between January 2015 and September 2018 were included in the study. Sex, age, cirrhosis etiology, Child-Pugh class, and MELD scores were recorded. TLR1 and NOD2 polymorphisms were studied by the PCR method.
HCC developed in 88 (31.4%) of the 280 patients who were followed up, either during the recruitment phase of our study or during the follow-up. The mean follow-up time of our patient group was 17.04 ± 11.72 months, and the mean follow-up time of HCC patients was 12.09 ± 10.26 months. TLR1 (rs5743551) polymorphism was associated with HCC development (P = .003). TLR1 (rs5743551) and NOD2 (rs2066844) polymorphisms were associated with the development of spontaneous bacterial peritonitis (SBP) in the HCC patient group (P = .013 and P = .021, respectively).
We think that increased bacterial translocation in cirrhotic patients may contribute to HCC development by causing chronic inflammation, especially in patients with TLR 1 (rs5743551) polymorphism.
肝细胞癌(HCC)是恶性肿瘤导致死亡的重要原因之一。Toll 样受体(TLR)在肝脏病理生理学中非常重要,因为它们在先天免疫系统中发挥作用,例如调节炎症、伤口愈合、刺激适应性免疫反应、促进上皮再生和致癌作用。在这项研究中,我们计划研究 TLR1(rs4833095、rs5743551)和核苷酸结合寡聚化结构域(NOD2)(rs2066844、rs2066845、rs2066847)多态性在 HCC 发展中的作用及其对 HCC 患者临床表型的影响。
我们的研究是前瞻性设计的。纳入 2015 年 1 月至 2018 年 9 月在我院随访的肝硬化和 HCC 患者。记录性别、年龄、肝硬化病因、Child-Pugh 分级和 MELD 评分。采用 PCR 法研究 TLR1 和 NOD2 多态性。
280 例随访患者中,88 例(31.4%)发生 HCC,有的在本研究的招募阶段,有的在随访阶段。患者组的平均随访时间为 17.04 ± 11.72 个月,HCC 患者的平均随访时间为 12.09 ± 10.26 个月。TLR1(rs5743551)多态性与 HCC 发生有关(P =.003)。TLR1(rs5743551)和 NOD2(rs2066844)多态性与 HCC 患者自发性细菌性腹膜炎(SBP)的发生有关(P =.013 和 P =.021)。
我们认为,肝硬化患者细菌易位增加可能通过引起慢性炎症导致 HCC 发展,尤其是在 TLR1(rs5743551)多态性患者中。