Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China.
Department of Blood Transfusion, Xiangya Hospital, Central South University, Changsha, China.
Clin Ther. 2020 Mar;42(3):439-447. doi: 10.1016/j.clinthera.2020.01.012. Epub 2020 Feb 15.
Hepatocellular carcinoma (HCC) is the seventh most commonly diagnosed cancer and the fourth-leading cause of cancer-related death worldwide. Chronic hepatitis B virus (HBV) is the leading cause of HCC in China. Emerging evidence suggests that long noncoding (lnc)-RNAs are deregulated and are involved in the development of HCC. Our previous study found that HBV X protein can promote HCC by altering lncRNA expression profiles. The purpose of this study was to investigate the expression of the lncRNA semaphorin 6A-antisense RNA 1 (SEMA6A-AS1) and its prognostic value in HBV-related HCC.
Samples of HCC tissues and adjacent nontumor tissues were collected from patients who were pathologically diagnosed with HBV-related HCC after hepatectomy. Eligible patients had not received preoperative radiotherapy, chemotherapy, or embolotherapy. Real-time quantitative reverse-transcription polymerase chain reaction was performed to evaluate the expression levels of SEMA6A-AS1 in all tissue specimens. The correlations between SEMA6A-AS1 expression and clinicopathologic characteristics were analyzed using the χ test and the Fisher exact test. Overall survival curves constructed by the Kaplan-Meier method and univariate analysis made by Cox proportional hazards modeling were used for determining the prognostic significance of SEMA6A-AS1.
Specimens were collected from 47 patients (45 men, 2 women; mean age, 48.4 [10.7] years). SEMA6A-AS1 expression was significantly downregulated in HBV-related HCC tissues compared with that in adjacent noncancerous hepatic tissues (P < 0.01). Low levels of SEMA6A-AS1 were correlated with high α-fetoprotein level (P = 0.002), high Edmondson-Steiner tumor grade (P = 0.047), high tumor node metastasis stage (P = 0.01), capsular invasion (P = 0.005), and poor clinical response (P = 0.002). Additionally, both Kaplan-Meier estimator and univariate Cox regression analysis revealed that low SEMA6A-AS1 expression was significantly associated with poor overall survival (P < 0.05).
The results show that low expression of SEMA6A-AS1 was associated with a poor prognosis in patients with HBV-related HCC. It is necessary to determine the function and mechanism of SEMA6A-AS1 in HCC in order to identify it as a prognostic biomarker and therapeutic target.
肝细胞癌（HCC）是全球第七种最常见的癌症，也是癌症相关死亡的第四大主要原因。在中国，慢性乙型肝炎病毒（HBV）是 HCC 的主要病因。新出现的证据表明，长链非编码（lnc）RNAs 失调并参与 HCC 的发生。我们之前的研究发现，HBV X 蛋白可以通过改变 lncRNA 表达谱来促进 HCC。本研究旨在探讨乙型肝炎病毒相关 HCC 中 lncRNA 神经丝蛋白 6A 反义 RNA 1（SEMA6A-AS1）的表达及其预后价值。
从经病理诊断为乙型肝炎病毒相关 HCC 并接受肝切除术的患者中收集 HCC 组织和相邻非肿瘤组织样本。符合条件的患者术前未接受放疗、化疗或栓塞治疗。采用实时定量逆转录聚合酶链反应（qRT-PCR）检测所有组织标本中 SEMA6A-AS1 的表达水平。采用卡方检验和 Fisher 确切检验分析 SEMA6A-AS1 表达与临床病理特征的相关性。Kaplan-Meier 法构建总生存曲线和 Cox 比例风险模型进行单因素分析，以确定 SEMA6A-AS1 的预后意义。
共收集 47 例患者（男 45 例，女 2 例；平均年龄 48.4[10.7]岁）的标本。与相邻非癌性肝组织相比，HBV 相关 HCC 组织中 SEMA6A-AS1 的表达显著下调（P<0.01）。低水平的 SEMA6A-AS1 与高甲胎蛋白水平（P=0.002）、高 Edmondson-Steiner 肿瘤分级（P=0.047）、高肿瘤淋巴结转移分期（P=0.01）、包膜侵犯（P=0.005）和临床反应不良（P=0.002）相关。此外，Kaplan-Meier 估计和单因素 Cox 回归分析均显示，低 SEMA6A-AS1 表达与总生存期不良显著相关（P<0.05）。
研究结果表明，SEMA6A-AS1 低表达与 HBV 相关 HCC 患者预后不良相关。有必要确定 SEMA6A-AS1 在 HCC 中的功能和机制，以将其确定为预后生物标志物和治疗靶点。
