The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy
Abstract 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‐associa...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-09-01
|
| Series: | The Journal of Pathology: Clinical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cjp2.288 |
| _version_ | 1811315554194030592 |
|---|---|
| author | Christopher M Heaphy Corinne E Joshu John R Barber Christine Davis Jiayun Lu Reza Zarinshenas Edward Giovannucci Lorelei A Mucci Meir J Stampfer Misop Han Angelo M De Marzo Tamara L Lotan Elizabeth A Platz Alan K Meeker |
| author_facet | Christopher M Heaphy Corinne E Joshu John R Barber Christine Davis Jiayun Lu Reza Zarinshenas Edward Giovannucci Lorelei A Mucci Meir J Stampfer Misop Han Angelo M De Marzo Tamara L Lotan Elizabeth A Platz Alan K Meeker |
| author_sort | Christopher M Heaphy |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T11:33:27Z |
| format | Article |
| id | doaj.art-d83e9cf0b5244fd6a2439370f8fc6cb4 |
| institution | Directory Open Access Journal |
| issn | 2056-4538 |
| language | English |
| last_indexed | 2024-04-13T11:33:27Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Journal of Pathology: Clinical Research |
| spelling | doaj.art-d83e9cf0b5244fd6a2439370f8fc6cb42022-12-22T02:48:31ZengWileyThe Journal of Pathology: Clinical Research2056-45382022-09-018548149110.1002/cjp2.288The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomyChristopher M Heaphy0Corinne E Joshu1John R Barber2Christine Davis3Jiayun Lu4Reza Zarinshenas5Edward Giovannucci6Lorelei A Mucci7Meir J Stampfer8Misop Han9Angelo M De Marzo10Tamara L Lotan11Elizabeth A Platz12Alan K Meeker13Department of Pathology Johns Hopkins University School of Medicine Baltimore MD USASidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore MD USADepartment of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USADepartment of Pathology Johns Hopkins University School of Medicine Baltimore MD USADepartment of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USADepartment of Pathology Johns Hopkins University School of Medicine Baltimore MD USADepartment of Nutrition Harvard T.H. Chan School of Public Health Boston MA USADepartment of Epidemiology Harvard T.H. Chan School of Public Health Boston MA USADepartment of Nutrition Harvard T.H. Chan School of Public Health Boston MA USASidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore MD USADepartment of Pathology Johns Hopkins University School of Medicine Baltimore MD USADepartment of Pathology Johns Hopkins University School of Medicine Baltimore MD USASidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore MD USADepartment of Pathology Johns Hopkins University School of Medicine Baltimore MD USAAbstract 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.https://doi.org/10.1002/cjp2.288biomarkerprognosisprostate cancermetastasistelomeres |
| spellingShingle | Christopher M Heaphy Corinne E Joshu John R Barber Christine Davis Jiayun Lu Reza Zarinshenas Edward Giovannucci Lorelei A Mucci Meir J Stampfer Misop Han Angelo M De Marzo Tamara L Lotan Elizabeth A Platz Alan K Meeker The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy The Journal of Pathology: Clinical Research biomarker prognosis prostate cancer metastasis telomeres |
| 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 | biomarker prognosis prostate cancer metastasis telomeres |
| url | https://doi.org/10.1002/cjp2.288 |
| work_keys_str_mv | AT christophermheaphy theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT corinneejoshu theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT johnrbarber theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT christinedavis theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT jiayunlu theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT rezazarinshenas theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT edwardgiovannucci theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT loreleiamucci theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT meirjstampfer theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT misophan theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT angelomdemarzo theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT tamarallotan theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT elizabethaplatz theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT alankmeeker theprostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT christophermheaphy prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT corinneejoshu prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT johnrbarber prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT christinedavis prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT jiayunlu prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT rezazarinshenas prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT edwardgiovannucci prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT loreleiamucci prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT meirjstampfer prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT misophan prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT angelomdemarzo prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT tamarallotan prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT elizabethaplatz prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy AT alankmeeker prostatetissuebasedtelomerebiomarkerasaprognostictoolformetastasisanddeathfromprostatecancerafterprostatectomy |