PMID- 28833123
OWN - NLM
STAT- MEDLINE
DCOM- 20171204
LR  - 20190129
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 243
IP  - 4
DP  - 2017 Dec
TI  - Telomere length variation in tumor cells and cancer-associated fibroblasts: 
      potential biomarker for hepatocellular carcinoma.
PG  - 407-417
LID - 10.1002/path.4961 [doi]
AB  - The role of telomere dysfunction and aberrant telomerase activities in 
      hepatocellular carcinoma (HCC) has been overlooked for many years. This study 
      aimed to delineate the variation and prognostic value of telomere length in HCC. 
      Telomere-specific fluorescence in situ hybridization (FISH) and qPCR were used to 
      evaluate telomere length in HCC cell lines, tumor tissues, and isolated non-tumor 
      cells within the tumor. Significant telomere attrition was found in tumor cells 
      and cancer-associated fibroblasts (CAFs) compared to their normal counterparts, 
      but not in intratumor leukocytes or bile duct epithelial cells. Clinical 
      relevance and prognostic value of telomere length were investigated on tissue 
      microarrays of 257 surgically treated HCC patients. Reduced intensity of telomere 
      signals in tumor cells or CAFs correlated with larger tumor size and the presence 
      of vascular invasion (p < 0.05). Shortened telomeres in tumor cells or CAFs 
      associated with reduced survival and increased recurrence, and were identified as 
      independent prognosticators for HCC patients (p < 0.05). These findings were 
      validated in an independent HCC cohort of 371 HCC patients from The Cancer Genome 
      Atlas (TCGA) database, confirming telomere attrition and its prognostic value in 
      HCC. We also showed that telomerase reverse transcriptase promoter (TERTp) 
      mutation correlated with telomere shortening in HCC. Telomere variation in tumor 
      cells and non-tumor cells within the tumor microenvironment of HCC was a valuable 
      prognostic biomarker for this fatal malignancy. (c) 2017 The Authors. The Journal 
      of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society 
      of Great Britain and Ireland.
CI  - (c) 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd 
      on behalf of Pathological Society of Great Britain and Ireland.
FAU - Ma, Li-Jie
AU  - Ma LJ
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Wang, Xiao-Ying
AU  - Wang XY
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Duan, Meng
AU  - Duan M
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Liu, Long-Zi
AU  - Liu LZ
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Shi, Jie-Yi
AU  - Shi JY
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Dong, Liang-Qing
AU  - Dong LQ
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Yang, Liu-Xiao
AU  - Yang LX
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Wang, Zhi-Chao
AU  - Wang ZC
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Ding, Zhen-Bin
AU  - Ding ZB
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Ke, Ai-Wu
AU  - Ke AW
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Cao, Ya
AU  - Cao Y
AD  - Cancer Research Institute, Xiangya School of Medicine, Central South University, 
      Hunan, PR China.
FAU - Zhang, Xiao-Ming
AU  - Zhang XM
AD  - Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of 
      Shanghai, Chinese Academy of Sciences, Shanghai, PR China.
FAU - Zhou, Jian
AU  - Zhou J
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Fan, Jia
AU  - Fan J
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
FAU - Gao, Qiang
AU  - Gao Q
AD  - Department of Liver Surgery and Transplantation, Liver Cancer Institute, 
      Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion 
      (Ministry of Education), Fudan University, Shanghai, PR China.
AD  - State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, PR 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171013
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - EC 2.7.7.49 (TERT protein, human)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Cancer-Associated Fibroblasts/*metabolism/pathology
MH  - Carcinoma, Hepatocellular/genetics/*metabolism/pathology/therapy
MH  - Cell Line, Tumor
MH  - Chi-Square Distribution
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Kaplan-Meier Estimate
MH  - Liver Neoplasms/genetics/*metabolism/pathology/therapy
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Mutation
MH  - Neoplasm Recurrence, Local
MH  - Promoter Regions, Genetic
MH  - Proportional Hazards Models
MH  - Real-Time Polymerase Chain Reaction
MH  - Telomerase/genetics/metabolism
MH  - Telomere/genetics/*metabolism/pathology
MH  - *Telomere Homeostasis
MH  - *Telomere Shortening
MH  - Treatment Outcome
MH  - Tumor Microenvironment
PMC - PMC5725724
OTO - NOTNLM
OT  - FISH
OT  - TERTp
OT  - hepatocellular carcinoma
OT  - prognosis
OT  - telomere length
EDAT- 2017/08/24 06:00
MHDA- 2017/12/05 06:00
PMCR- 2017/12/12
CRDT- 2017/08/24 06:00
PHST- 2017/03/20 00:00 [received]
PHST- 2017/08/03 00:00 [revised]
PHST- 2017/08/16 00:00 [accepted]
PHST- 2017/08/24 06:00 [pubmed]
PHST- 2017/12/05 06:00 [medline]
PHST- 2017/08/24 06:00 [entrez]
PHST- 2017/12/12 00:00 [pmc-release]
AID - PATH4961 [pii]
AID - 10.1002/path.4961 [doi]
PST - ppublish
SO  - J Pathol. 2017 Dec;243(4):407-417. doi: 10.1002/path.4961. Epub 2017 Oct 13.