1. Significance of TERT Genetic Alterations and Telomere Length in Hepatocellular Carcinoma
- Author
-
Changmin Kim, Hye Seon Kim, Seung Kew Yoon, Jeong-Won Jang, Si-Hyun Bae, Jin Young Park, Kwon-Yong Tak, Jong-Young Choi, Soon-Kyu Lee, Heechul Nam, Pil-Soo Sung, and Jin-Seoub Kim
- Subjects
telomere ,Cancer Research ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,biomarkers ,AKT1 ,HCCS ,Biology ,medicine.disease ,Telomere ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Gene expression ,liver neoplasm ,treatment outcome ,medicine ,Cancer research ,030211 gastroenterology & hepatology ,Liver neoplasm ,Telomerase reverse transcriptase ,Gene ,RC254-282 ,TERT - Abstract
Telomerase reverse transcriptase (TERT) mutations are reportedly the most frequent somatic genetic alterations in hepatocellular carcinoma (HCC). An integrative analysis of TERT-telomere signaling during hepatocarcinogenesis is lacking. This study aimed to investigate the clinicopathological association and prognostic value of TERT gene alterations and telomere length in HCC patients undergoing hepatectomy as well as transarterial chemotherapy (TACE). TERT 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 TERT. The PPI analysis identified eight key TERT-interacting genes, namely CCT5, TUBA1B, mTOR, RPS6KB1, AKT1, WHAZ, YWHAQ, and TERT. Among these, TERT was the most strongly differentially expressed gene. TERT promoter mutations were more frequent, TERT expression was significantly higher, and telomere length was longer in tumors versus non-tumors. TERT promoter mutations were most frequent in HCV-related HCCs and less frequent in HBV-related HCCs. TERT promoter mutations were associated with higher TERT levels and longer telomere length and were an independent predictor of worse overall survival after hepatectomy. TERT expression was positively correlated with tumor differentiation and stage progression, and independently predicted shorter time to progression after TACE. The TERT-telomere network may have a crucial role in the development and progression of HCC. TERT-telomere abnormalities might serve as useful biomarkers for HCC, but the prognostic values may differ with tumor characteristics and treatment.
- Published
- 2021