原发性肝细胞癌术后复发转移患者长链非编码RNA的表达分析

Expressions of long non-coding RNAs in patients with primary hepatocellular carcinoma of recurrent or / and metastasis after surgical resection

目的分析原发性肝细胞癌(HCC)术后复发转移患者长链非编码RNA(lncRNA)的表达情况。方法纳入2010年7月至2012年9月四川省人民医院收治的32例术后3年内局部复发、22例远处转移、17例局部(肝内)复发合并远处转移和56例无瘤生存的HCC患者,采用原位杂交法测定其手术原发肿瘤组织、癌旁正常组织和复发转移灶中肌动蛋白丝相关蛋白1-反义RNA1(AFAP1-AS1)、肝癌微血管浸润相关lncRNA(MVIH)和肺腺癌转移相关转录本1(MALAT-1)的表达分布,比较它们在癌旁正常组织、原发肿瘤灶和转移复发灶中的表达差异。结果AFAP1-AS1、MVIH和MALAT-1均主要定位于细胞质中。AFAP-AS1在原发肿瘤组织中的表达下调,显著低于癌旁正常组织(P均<0.01);在复发转移瘤样本中AFAP-AS1表达与原发肿瘤组织相近(P均>0.05)。MVIH在原发肿瘤组织中的表达上调,显著高于癌旁正常组织(P<0.01,P<0.05),在发生远处转移患者原发肿瘤组织中MVIH的表达显著高于无瘤生存患者的原发肿瘤组织(P<0.05),发生远处转移患者远处转移灶中MVIH表达显著高于其原发肿瘤组织(P<0.05)。MALAT-1在原发肿瘤组织中的表达上调,显著高于癌旁正常组织(P<0.01,P<0.05);发生局部复发、远处转移及复发合并转移患者原发肿瘤组织中的MALAT-1均显著高于无瘤生存患者的原发肿瘤组织(P均<0.05);而复发转移瘤灶中的MALAT-1表达与原发肿瘤组织相近(P>0.05)。结论 AFAP1-AS1、MVIH和MALAT-1等三种lncRNA与HCC的发生发展密切相关,MVIH和MALAT-1的过度上调与HCC的复发转移有关。

Objective To analyze the expressions of long non-coding RNAs（ lncRNA） in patients with primary hepatocellular carcinoma（ HCC） of recurrent or / and metastasis after surgical resection. Methods Thirty-two patients with local recurrence within 3 years after operation,22 with distant metastasis,17 with intrahepatic local recurrence combined with distant metastasis and 56 with tumor-free survival who were received and treated in Sichuan Provincial People＇ s Hospital between July 2010 and September 2012 were included in this study. The hybridization in situ method was used to detect the expressions of actin filament associated protein 1- antisense RNA1（ AFAP1-AS1）,lncRNA associated with microvascular invasion in HCC（ MVIH） and metastasis associated lung adenocarcinoma transcript 1（ MALAT-1） in the primary tumor tissues,normal tissues adjacent to cancer and the tissues of recurrent / metastatic lesions,and their expression levels in these tissues were compared. Results AFAP1-AS1,MVIH and MALAT-1 were mainly located in the cytoplasm. AFAP-AS1 expression in primary tumor tissue was down-regulated and was significantly lower than that in normal tissues adjacent to cancer（ all P〈0. 01）; AFAP-AS1 expression in recurrent or / and metastatic tumor tissues was similar with that in primary tumor tissues（ all P〉0. 05）. MVIH expression in primary tumor tissues was up-regulated and was significantly higher than that in normal tissues adjacent to cancer（ P〈0. 01,P〈0. 05）; MVIH expression in primary tumor tissues of distant metastasis patients was significantly higher than that in primary tumor tissues of tumor-free survival patients（ P〈0. 05）; MVIHexpression level in distant metastasis foci of patients with distant metastasis was significantly higher than that in the primary tumor tissues（ P〈0. 05）. MALAT-1 expression level in primary tumor tissues was up-regulated and was significantly higher than that in normal tissues adjacent to cancer（ P〈0. 01,P〈0. 05）; MALAT-1 expression levels in primary tumor tissues of patients with local recurrence,distant metastasis and recurrence combined with metastasis were significantly higher than that in primary tumor tissues of tumor-free survival patients（ all P〈0. 05）; MALAT-1 expression level in the foci of recurrent or / and metastatic tumor was similar with that in primary tumor tissues（ P〉0. 05）. Conclusions AFAP1-AS1,MVIH and MALAT-1 belonging to lncRNA are closely correlated with occurrence and development of HCC,in which MVIH and MALAT-1 over up-regulations are associated with recurrence and metastasis of HCC.