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Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the United States

BACKGROUND: Telomere shortening is an important molecular event in hepatocellular carcinoma (HCC) initiation; however, its role in HCC progression and prognosis is less clear. Our study aimed to examine the association of telomere length with survival of patients with HCC. METHODS: We measured telom...

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Autores principales: Yang, Baiyu, Shebl, Fatma M., Sternberg, Lawrence R., Warner, Andrew C., Kleiner, David E., Edelman, Daniel C., Gomez, Allison, Dagnall, Casey L., Hicks, Belynda D., Altekruse, Sean F., Hernandez, Brenda Y., Lynch, Charles F., Meltzer, Paul S., McGlynn, Katherine A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120796/
https://www.ncbi.nlm.nih.gov/pubmed/27880792
http://dx.doi.org/10.1371/journal.pone.0166828
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author Yang, Baiyu
Shebl, Fatma M.
Sternberg, Lawrence R.
Warner, Andrew C.
Kleiner, David E.
Edelman, Daniel C.
Gomez, Allison
Dagnall, Casey L.
Hicks, Belynda D.
Altekruse, Sean F.
Hernandez, Brenda Y.
Lynch, Charles F.
Meltzer, Paul S.
McGlynn, Katherine A.
author_facet Yang, Baiyu
Shebl, Fatma M.
Sternberg, Lawrence R.
Warner, Andrew C.
Kleiner, David E.
Edelman, Daniel C.
Gomez, Allison
Dagnall, Casey L.
Hicks, Belynda D.
Altekruse, Sean F.
Hernandez, Brenda Y.
Lynch, Charles F.
Meltzer, Paul S.
McGlynn, Katherine A.
author_sort Yang, Baiyu
collection PubMed
description BACKGROUND: Telomere shortening is an important molecular event in hepatocellular carcinoma (HCC) initiation; however, its role in HCC progression and prognosis is less clear. Our study aimed to examine the association of telomere length with survival of patients with HCC. METHODS: We measured telomere length in tumor and adjacent non-tumor tissues from 126 persons with HCC in the United States (U.S.) who were followed for mortality outcomes. Relative telomere length (RTL) was measured by a monochrome multiplex quantitative polymerase chain reaction assay. Multivariable Cox proportional hazards modeling was used to calculate hazard ratios (HRs) and 95% CIs for the association between telomere length and all-cause mortality. We also examined associations between telomere length and patient characteristics using multiple linear regression. RESULTS: During a mean follow-up of 6.0 years, 79 deaths occurred among 114 individuals for whom survival data were available. The ratio of RTL in tumor relative to non-tumor tissue was greater for individuals with regional or distant stage tumors (0.97) than localized stage tumors (0.77), and for individuals with grade III or IV tumors (0.95) than grade II (0.88) or grade I (0.67) tumors. An RTL ratio ≥1 was not associated with survival (HR 0.92, 95% CI 0.55, 1.55) compared to a ratio <1, after adjusting for age at diagnosis, sex, tumor stage and tumor size. Similarly, RTL in the tumor and non-tumor tissue, respectively, were not associated with survival. CONCLUSIONS: This U.S. based study found that telomeres may be longer in more aggressive HCCs. There was no evidence, however, that telomere length was associated with survival of patients with HCC. Future investigations are warranted to clarify the role of telomere length in HCC prognosis.
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spelling pubmed-51207962016-12-15 Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the United States Yang, Baiyu Shebl, Fatma M. Sternberg, Lawrence R. Warner, Andrew C. Kleiner, David E. Edelman, Daniel C. Gomez, Allison Dagnall, Casey L. Hicks, Belynda D. Altekruse, Sean F. Hernandez, Brenda Y. Lynch, Charles F. Meltzer, Paul S. McGlynn, Katherine A. PLoS One Research Article BACKGROUND: Telomere shortening is an important molecular event in hepatocellular carcinoma (HCC) initiation; however, its role in HCC progression and prognosis is less clear. Our study aimed to examine the association of telomere length with survival of patients with HCC. METHODS: We measured telomere length in tumor and adjacent non-tumor tissues from 126 persons with HCC in the United States (U.S.) who were followed for mortality outcomes. Relative telomere length (RTL) was measured by a monochrome multiplex quantitative polymerase chain reaction assay. Multivariable Cox proportional hazards modeling was used to calculate hazard ratios (HRs) and 95% CIs for the association between telomere length and all-cause mortality. We also examined associations between telomere length and patient characteristics using multiple linear regression. RESULTS: During a mean follow-up of 6.0 years, 79 deaths occurred among 114 individuals for whom survival data were available. The ratio of RTL in tumor relative to non-tumor tissue was greater for individuals with regional or distant stage tumors (0.97) than localized stage tumors (0.77), and for individuals with grade III or IV tumors (0.95) than grade II (0.88) or grade I (0.67) tumors. An RTL ratio ≥1 was not associated with survival (HR 0.92, 95% CI 0.55, 1.55) compared to a ratio <1, after adjusting for age at diagnosis, sex, tumor stage and tumor size. Similarly, RTL in the tumor and non-tumor tissue, respectively, were not associated with survival. CONCLUSIONS: This U.S. based study found that telomeres may be longer in more aggressive HCCs. There was no evidence, however, that telomere length was associated with survival of patients with HCC. Future investigations are warranted to clarify the role of telomere length in HCC prognosis. Public Library of Science 2016-11-23 /pmc/articles/PMC5120796/ /pubmed/27880792 http://dx.doi.org/10.1371/journal.pone.0166828 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Yang, Baiyu
Shebl, Fatma M.
Sternberg, Lawrence R.
Warner, Andrew C.
Kleiner, David E.
Edelman, Daniel C.
Gomez, Allison
Dagnall, Casey L.
Hicks, Belynda D.
Altekruse, Sean F.
Hernandez, Brenda Y.
Lynch, Charles F.
Meltzer, Paul S.
McGlynn, Katherine A.
Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the United States
title Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the United States
title_full Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the United States
title_fullStr Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the United States
title_full_unstemmed Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the United States
title_short Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the United States
title_sort telomere length and survival of patients with hepatocellular carcinoma in the united states
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120796/
https://www.ncbi.nlm.nih.gov/pubmed/27880792
http://dx.doi.org/10.1371/journal.pone.0166828
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