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The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy
Current biomarkers are inadequate prognostic predictors in localized prostate cancer making treatment decision‐making challenging. Previously, we observed that the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer‐associated strom...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353659/ https://www.ncbi.nlm.nih.gov/pubmed/35836303 http://dx.doi.org/10.1002/cjp2.288 |
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author | Heaphy, Christopher M Joshu, Corinne E Barber, John R Davis, Christine Lu, Jiayun Zarinshenas, Reza Giovannucci, Edward Mucci, Lorelei A Stampfer, Meir J Han, Misop De Marzo, Angelo M Lotan, Tamara L Platz, Elizabeth A Meeker, Alan K |
author_facet | Heaphy, Christopher M Joshu, Corinne E Barber, John R Davis, Christine Lu, Jiayun Zarinshenas, Reza Giovannucci, Edward Mucci, Lorelei A Stampfer, Meir J Han, Misop De Marzo, Angelo M Lotan, Tamara L Platz, Elizabeth A Meeker, Alan K |
author_sort | Heaphy, Christopher M |
collection | PubMed |
description | Current biomarkers are inadequate prognostic predictors in localized prostate cancer making treatment decision‐making challenging. Previously, we observed that the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer‐associated stromal cells – the telomere biomarker – is strongly associated with progression to metastasis and prostate cancer death after prostatectomy independent of currently used pathologic indicators. Here, we optimized our method allowing for semi‐automated telomere length determination in single cells in fixed tissue, and tested the telomere biomarker in five cohort studies of men surgically treated for clinically localized disease (N = 2,255). We estimated the relative risk (RR) of progression to metastasis (N = 311) and prostate cancer death (N = 85) using models appropriate to each study's design adjusting for age, prostatectomy stage, and tumor grade, which then we meta‐analyzed using inverse variance weights. Compared with men who had less variable telomere length among prostate cancer cells and longer telomere length in prostate cancer‐associated stromal cells, men with the combination of more variable and shorter telomere length had 3.76 times the risk of prostate cancer death (95% confidence interval [CI] 1.37–10.3, p = 0.01) and had 2.23 times the risk of progression to metastasis (95% CI 0.99–5.02, p = 0.05). The telomere biomarker was associated with prostate cancer death in men with intermediate risk disease (grade groups 2/3: RR = 9.18, 95% CI 1.14–74.0, p = 0.037) and with PTEN protein intact tumors (RR = 6.74, 95% CI 1.46–37.6, p = 0.015). In summary, the telomere biomarker is robust and associated with poor outcome independent of current pathologic indicators in surgically treated men. |
format | Online Article Text |
id | pubmed-9353659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93536592022-08-09 The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy Heaphy, Christopher M Joshu, Corinne E Barber, John R Davis, Christine Lu, Jiayun Zarinshenas, Reza Giovannucci, Edward Mucci, Lorelei A Stampfer, Meir J Han, Misop De Marzo, Angelo M Lotan, Tamara L Platz, Elizabeth A Meeker, Alan K J Pathol Clin Res Original Articles Current biomarkers are inadequate prognostic predictors in localized prostate cancer making treatment decision‐making challenging. Previously, we observed that the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer‐associated stromal cells – the telomere biomarker – is strongly associated with progression to metastasis and prostate cancer death after prostatectomy independent of currently used pathologic indicators. Here, we optimized our method allowing for semi‐automated telomere length determination in single cells in fixed tissue, and tested the telomere biomarker in five cohort studies of men surgically treated for clinically localized disease (N = 2,255). We estimated the relative risk (RR) of progression to metastasis (N = 311) and prostate cancer death (N = 85) using models appropriate to each study's design adjusting for age, prostatectomy stage, and tumor grade, which then we meta‐analyzed using inverse variance weights. Compared with men who had less variable telomere length among prostate cancer cells and longer telomere length in prostate cancer‐associated stromal cells, men with the combination of more variable and shorter telomere length had 3.76 times the risk of prostate cancer death (95% confidence interval [CI] 1.37–10.3, p = 0.01) and had 2.23 times the risk of progression to metastasis (95% CI 0.99–5.02, p = 0.05). The telomere biomarker was associated with prostate cancer death in men with intermediate risk disease (grade groups 2/3: RR = 9.18, 95% CI 1.14–74.0, p = 0.037) and with PTEN protein intact tumors (RR = 6.74, 95% CI 1.46–37.6, p = 0.015). In summary, the telomere biomarker is robust and associated with poor outcome independent of current pathologic indicators in surgically treated men. John Wiley & Sons, Inc. 2022-07-14 /pmc/articles/PMC9353659/ /pubmed/35836303 http://dx.doi.org/10.1002/cjp2.288 Text en © 2022 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Heaphy, Christopher M Joshu, Corinne E Barber, John R Davis, Christine Lu, Jiayun Zarinshenas, Reza Giovannucci, Edward Mucci, Lorelei A Stampfer, Meir J Han, Misop De Marzo, Angelo M Lotan, Tamara L Platz, Elizabeth A Meeker, Alan K The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy |
title | The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy |
title_full | The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy |
title_fullStr | The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy |
title_full_unstemmed | The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy |
title_short | The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy |
title_sort | prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353659/ https://www.ncbi.nlm.nih.gov/pubmed/35836303 http://dx.doi.org/10.1002/cjp2.288 |
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