Jang Jeong-Won, Kim Jin-Seoub, Kim Hye-Seon, Tak Kwon-Yong, Lee Soon-Kyu, Nam Hee-Chul, Sung Pil-Soo, Kim Chang-Min, Park Jin-Young, Bae Si-Hyun, Choi Jong-Young, Yoon Seung-Kew
Department of Internal Medicine, Collage of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, Collage of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Cancers (Basel). 2021 Apr 30;13(9):2160. doi: 10.3390/cancers13092160.
Telomerase reverse transcriptase () mutations are reportedly the most frequent somatic genetic alterations in hepatocellular carcinoma (HCC). An integrative analysis of -telomere signaling during hepatocarcinogenesis is lacking. This study aimed to investigate the clinicopathological association and prognostic value of gene alterations and telomere length in HCC patients undergoing hepatectomy as well as transarterial chemotherapy (TACE). promoter mutation, expression, and telomere length were analyzed by Sanger sequencing and real-time PCR in 305 tissue samples. Protein-protein interaction (PPI) analysis was performed to identify a set of genes that physically interact with . The PPI analysis identified eight key -interacting genes, namely , , , , , , , and . Among these, was the most strongly differentially expressed gene. promoter mutations were more frequent, expression was significantly higher, and telomere length was longer in tumors versus non-tumors. promoter mutations were most frequent in HCV-related HCCs and less frequent in HBV-related HCCs. promoter mutations were associated with higher levels and longer telomere length and were an independent predictor of worse overall survival after hepatectomy. expression was positively correlated with tumor differentiation and stage progression, and independently predicted shorter time to progression after TACE. The -telomere network may have a crucial role in the development and progression of HCC. -telomere abnormalities might serve as useful biomarkers for HCC, but the prognostic values may differ with tumor characteristics and treatment.
据报道，端粒酶逆转录酶（）突变是肝细胞癌（HCC）中最常见的体细胞遗传改变。目前缺乏对肝癌发生过程中端粒信号传导的综合分析。本研究旨在探讨接受肝切除术以及经动脉化疗栓塞（TACE）的HCC患者中基因改变和端粒长度的临床病理相关性及预后价值。通过Sanger测序和实时PCR对305份组织样本分析启动子突变、表达及端粒长度。进行蛋白质-蛋白质相互作用（PPI）分析以鉴定一组与物理相互作用的基因。PPI分析鉴定出八个关键的相互作用基因，即、、、、、、和。其中，是差异表达最显著的基因。与非肿瘤相比，肿瘤中启动子突变更频繁，表达显著更高，端粒长度更长。启动子突变在丙型肝炎病毒（HCV）相关HCC中最常见，在乙型肝炎病毒（HBV）相关HCC中较少见。启动子突变与更高水平和更长端粒长度相关，并且是肝切除术后总体生存较差的独立预测因素。表达与肿瘤分化和分期进展呈正相关，并且独立预测TACE后较短的进展时间。端粒网络可能在HCC的发生和发展中起关键作用。端粒异常可能是HCC有用的生物标志物，但预后价值可能因肿瘤特征和治疗而异。
