Promoter mutations and cellular distribution of telomerase in non-clear cell and clear cell hepatocellular carcinoma
| Autor: | Xia Li, Wen Wen, Rui Yao, Jing Zhang, Huijie Bian, Zhi-Nan Chen, Han-Qiang Liu, Pei Wang, Ling Wang, Can Li, Wan Huang, Changsheng Chen, Yuan Yang, Weiping Zhou, Yu-Kui Shang |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Telomerase Carcinoma Hepatocellular Intracellular Space non-clear cell hepatocellular carcinoma medicine.disease_cause telomerase 03 medical and health sciences 0302 clinical medicine Recurrence subcellular localization Medicine Humans Telomerase reverse transcriptase Promoter Regions Genetic Aged Neoplasm Staging Mutation business.industry Liver Neoplasms HCCS Middle Aged Telomere medicine.disease Molecular medicine Survival Analysis digestive system diseases Protein Transport 030104 developmental biology Oncology 030220 oncology & carcinogenesis Hepatocellular carcinoma Clear Cell Hepatocellular Carcinoma Cancer research Female Neoplasm Grading business Clear cell clear cell hepatocellular carcinoma Research Paper Adenocarcinoma Clear Cell Follow-Up Studies |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Wan Huang 1, * , Weiping Zhou 2, * , Can Li 1, * , Yuan Yang 2 , Yu-Kui Shang 1 , Changsheng Chen 3 , Jing Zhang 4 , Rui Yao 1 , Pei Wang 1 , Wen Wen 1 , Han-Qiang Liu 5 , Ling Wang 3 , Xia Li 4 , Huijie Bian 1 , Zhi-Nan Chen 1 1 National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an, China 2 The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China 3 Department of Health Statistics, Fourth Military Medical University, Xi'an, China 4 Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, China 5 Department of Nutrition and Food Hygiene, Fourth Military Medical University, Xi'an, China * Shared first authors Correspondence to: Zhi-Nan Chen, email: znchen@fmmu.edu.cn Huijie Bian, email: hjbian@fmmu.edu.cn Keywords: telomerase, subcellular localization, mutation, non-clear cell hepatocellular carcinoma, clear cell hepatocellular carcinoma Received: July 20, 2016 Accepted: February 07, 2017 Published: February 17, 2017 ABSTRACT Reactivation of telomerase is a critical step in the development of hepatocellular carcinoma (HCC). Here we identified the frequency of mutations in telomerase reverse transcriptase (TERT) promoter was 34% in non-clear cell HCC (NCCHCC, n = 259) and 26.3% in clear cell HCC (CCHCC, n = 57). The mutations were independently associated with poor recurrence-free survival of HCCs. Interestingly immunohistochemical analysis demonstrated a higher positive rate of TERT cytoplasmic localization (95%) than nuclear localization (64%) in HCCs. In NCCHCCs, the mutations correlated with higher TERT nuclear expression and increased telomere-dependent telomerase activity. Higher cytoplasmic expression was found in adjacent tissues compared to tumor tissues, and was associated with tumor well-differentiation and lower level of α-fetoprotein. NCCHCCs with low nuclear as well as high cytoplasmic expression correlated with better prognosis. In CCHCCs, elevated TERT cytoplasmic expression was observed in CCHCCs harboring mutations. Higher TERT cytoplasmic expression was found in tumor tissues compared to adjacent tissues, and was associated with multiple numbers of tumors and poor prognosis of CCHCCs. In conclusion, mutations in TERT promoter disclose the significance of both nuclear and cytoplasmic TERT in HCC. Cytoplasmic TERT should also be considered when determining prognosis and treatment of HCCs. |
| Databáze: | OpenAIRE |
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