肝细胞癌组织中ALDH1A1、miR-140-5p表达及其与化疗敏感性的关系

摘要/Abstract

摘要： 目的探讨乙醛脱氢酶1A1(ALDH1A1)、微小RNA-140-5p(miR-140-5p)在肝细胞癌(HCC)组织中的表达水平及其与化疗敏感性的关系。方法利用Ualcan数据库检索ALDH1A1在HCC组织和正常肝组织中的表达水平。选取2016年4月至2021年1月解放军北部战区总医院行肝动脉插管化疗栓塞(TACE)的Ⅲ期HCC患者91例,另选取非HCC受试者91例,均收集活检时留取的组织。实时荧光定量PCR(qRT-PCR)测定组织ALDH1A1 mRNA、miR-140-5p表达情况;分析HCC组织ALDH1A1 mRNA表达水平与miR-140-5p的相关性。依据TACE治疗效果分将HCC患者分为化疗耐药组(53例)和化疗敏感组(38例),分析HCC临床特征及HCC组织ALDH1A1、miR-140-5p表达水平与化疗敏感性的关系;分析HCC化疗敏感的影响因素。结果 Ualcan数据库显示,正常肝组织ALDH1A1 mRNA为(559.76±138.67),低于HCC组织(851.70±245.89)(P<0.05)。qRT-PCR法检测显示,非HCC患者组织ALDH1A1 mRNA为(1.01±0.34),低于HCC组(1.97±0.65)(P<0.05);miR-140-5p为(1.06±0.35),高于HCC组(0.50±0.17)(P<0.05);HCC组织中ALDH1A1 mRNA水平与miR-140-5p呈负相关(P<0.05)。化疗敏感组肿瘤多发、血清AFP≤ 20 μg/L、HCC组织ALDH1A1 mRNA≤1.97、HCC组织miR-140-5p>0.50的HCC患者占比高于化疗耐药组(P<0.05)。ALDH1A是影响HCC患者化疗敏感的独立危险因素(P<0.05),miR-140-5p是影响HCC患者化疗敏感的独立保护因素(P<0.05)。结论 HCC组织中ALDH1A1表达上调,miR-140-5p表达下调;ALDH1A1、miR-140-5p均与化疗敏感性有关,有望成为评估HCC患者化疗敏感性的指标。

关键词: 乙醛脱氢酶1A1, 肝细胞癌, 微小RNA-140-5p, 化疗敏感性

Abstract: Objective To investigate the expression levels of acetaldehyde dehydrogenase 1A1 (ALDH1A1) and microRNA-140-5p (miR-140-5p) in hepatocellular carcinoma (HCC) tissues and their relationship with chemotherapy sensitivity.Methods Ualcan database was used to search the expression level of ALDH1A1 in HCC tissues and normal liver tissues. Ninety-one patients with stage III HCC who underwent transcatheter hepatic arterial chemoembolization (TACE) from April 2016 to January 2021 were selected as HCC group, and ninety-one with non-HCC who underwent HCC screening were selected as control group, and the tissues were collected during the biopsy. The expression of ALDH1A1 mRNA and miR-140-5p in tissues was determined by real-time fluorescent quantitative PCR (qRT-PCR); the correlation between the expression level of ALDH1A1 mRNA in HCC tissue and miR-140-5p was analyzed; according to TACE treatment effect, HCC patients were divided into chemotherapy resistance group (53 cases) and chemotherapy sensitive group (38 cases), the relationship between the clinical characteristics of HCC, the expression levels of ALDH1A1 and miR-140-5p in HCC tissues and chemotherapy sensitivity were analyzed; the influencing factors of HCC chemotherapy sensitivity were analyzed.Results The Ualcan database showed that the expression level of ALDH1A1 mRNA (559.76±138.67) in normal liver tissues was lower than that in HCC tissues (851.70±245.89) (P<0.05). The qRT-PCR method showed that the expression level of ALDH1A1 mRNA (1.01±0.34) in the control group was lower than that in the HCC group (1.97±0.65) (P<0.05), and the expression level of miR-140-5p (1.06±0.35) was higher than that in the HCC group (0.50±0.17) (P<0.05); the level of ALDH1A1 mRNA in HCC tissues was negatively correlated with miR-140-5p (P<0.05); the proportions of HCC patients with multiple occurrences, serum AFP level ≤ 20 μg/L, relative expression of ALDH1A1 mRNA in HCC tissue ≤ 1.97, and relative expression of miR-140-5p in HCC tissue > 0.50 in the chemotherapy sensitive group were higher than those in the chemotherapy resistance group (P<0.05); ALDH1A was an independent risk factor that affected chemotherapy sensitivity of HCC patients (P<0.05), and miR-140-5p was an independent protective factor that affected chemotherapy sensitivity of HCC patients (P<0.05).Conclusion The expression of ALDH1A1 is up-regulated and the expression of miR-140-5p is down-regulated in HCC tissues. Both ALDH1A1 and miR-140-5p are related to chemotherapy sensitivity, and both are expected to be indicators for evaluating the chemotherapy sensitivity of HCC patients.

Key words: Acetaldehyde dehydrogenase 1A1, Hepatocellular carcinoma, MicroRNA-140-5p, Chemotherapy sensitivity

刘晓斌, 唐裕福, 陈明洋, 辛建, 张巍. 肝细胞癌组织中ALDH1A1、miR-140-5p表达及其与化疗敏感性的关系[J]. 肝脏, 2022, 27(4): 472-477.

LIU Xiao-bin, TANG Yu-fu, CHEN Ming-yang, XIN Jian, ZHANG Wei. The expression of ALDH1A1 and miR-140-5p in hepatocellular carcinoma and the relationship with chemotherapy sensitivity[J]. Chinese Hepatolgy, 2022, 27(4): 472-477.

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