1Department of Pathology; 2James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine; 3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health; 4Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland; Departments of 5Nutrition and 6Epidemiology, Harvard School of Public Health; and 7Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 8Department of Pathology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Cancer Discov. 2013 Oct;3(10):1130-41. doi: 10.1158/2159-8290.CD-13-0135. Epub 2013 Jun 18.
Current prognostic indicators are imperfect predictors of outcome in men with clinically localized prostate cancer. Thus, tissue-based markers are urgently needed to improve treatment and surveillance decision-making. Given that shortened telomeres enhance chromosomal instability and such instability is a hallmark of metastatic lesions, we hypothesized that alterations in telomere length in the primary cancer would predict risk of progression to metastasis and prostate cancer death. To test this hypothesis, we conducted a prospective cohort study of 596 surgically treated men who participated in the ongoing Health Professionals Follow-up Study. Men who had the combination of more variable telomere length among prostate cancer cells (cell-to-cell) and shorter telomere length in prostate cancer-associated stromal (CAS) cells were substantially more likely to progress to metastasis or die of their prostate cancer. These findings point to the translational potential of this telomere biomarker for prognostication and risk stratification for individualized therapeutic and surveillance strategies.
In this prospective study, the combination of more variable telomere length among cancer cells and shorter telomere length in CAS cells was strongly associated with progression to metastasis and prostate cancer death, pointing to the translational potential for prognostication and risk stratifi cation for individualized therapeutic and surveillance strategies.
目前的预后指标不能完美预测局限性前列腺癌患者的结局。因此，迫切需要组织标志物来改善治疗和监测决策。鉴于端粒缩短会增强染色体不稳定性，而这种不稳定性是转移病灶的标志，我们假设原发性肿瘤中端粒长度的改变将预测转移和前列腺癌死亡的风险。为了验证这一假设，我们对参加正在进行的健康专业人员随访研究的 596 名接受手术治疗的男性进行了前瞻性队列研究。在前列腺癌细胞（细胞间）端粒长度变化更大且前列腺癌相关基质（CAS）细胞中端粒长度较短的男性，更有可能进展为转移或死于前列腺癌。这些发现表明，这种端粒生物标志物具有预测和风险分层的转化潜力，适用于个体化治疗和监测策略。
在这项前瞻性研究中，癌细胞中端粒长度变化更大和 CAS 细胞中端粒长度较短的组合与转移和前列腺癌死亡的进展密切相关，这表明该端粒生物标志物具有预测和风险分层的转化潜力，适用于个体化治疗和监测策略。
