The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy

Year: 2022

Type: article

Abstract: ABSTRACT Purpose 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. Experimental Design We optimized our method allowing for semi-automated telomere length determination in single cells in fixed tissue, and tested the telomere biomarker in tissue microarrays from 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. Results 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% 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 intact tumors (RR=6.74, 95% CI 1.46-37.6, p=0.015). Conclusions The telomere biomarker is robust and associated with poor outcome independent of current pathologic indicators in surgically-treated men. Translational Relevance Current prognostic biomarkers in localized prostate cancer are inadequate imperfect predictors; therefore, new biomarkers are needed to improve the prognostic classification and management of these patients. In a five-cohort study, we confirmed that the tissue-based telomere biomarker – the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer-associated stromal cells – was associated with progression to metastasis and prostate cancer death independent of currently used prognostic indicators after prostatectomy for clinically-localized disease. Importantly, the telomere biomarker was associated with poor outcome in men with intermediate risk disease, as well as in men with intact PTEN tumors. Thus, this tissue-based telomere biomarker has the translational potential to improve treatment and surveillance decision-making.

Source: The Journal of Pathology Clinical Research

DOI: 10.1002/cjp2.288

Authors: 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

Institutions: Johns Hopkins University, Johns Hopkins Medicine, Sidney Kimmel Comprehensive Cancer Center, Brigham and Women's Hospital, Harvard University

Language: English

Topic: Prostate Cancer Treatment and Research

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,700

Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, Prostate Cancer Foundation, National Institutes of Health, National Cancer Institute, DOD Prostate Cancer Research Program

OpenAlex ID: W4285595569