For the population science project, we assembled an interdisciplinary team, co-led by applied (epidemiologist) and basic (telomere biologist) scientists, to verify a novel tissue biomarker for prostate cancer prognosis that we discovered - telomere length variability in prostate cancer cells combined with short telomere length in cancer-associated stromal cells (""""""""telomere biomarker""""""""). In our prospective cohort study, men with this combination had 14-times the risk of prostate cancer death;men without this combination rarely died of their cancer over 15 years. Due to the fact that current prognostic factors inadequately distinguish between aggressive and nonaggressive disease, new prognostic biomarkers that inform beyond the currently used clinico-pathologic factors are needed to enhance treatment and surveillance decision-making. We will address this important unmet clinical need for improved risk stratification for prostate cancer patients. While our prior findings point to the clinical utility of the telomere biomarker, we have completed only the discovery phase. Here, we propose to;1) Demonstrate the validity and reproducibility of an automated """"""""TELl-FISH"""""""" method, our FISH-based telomere length measurement tool, using the same prospective cohort study in which we made our discovery. A valid and reproducible high-throughput method for measuring the biomarker is needed for the proposed epidemiologic study on prognosis, and in future epidemiologic studies on eariy detection and active surveillance. 2) Conduct a nested case-control study to verify the association between the telomere biomarker, assessed using automated TELl-FISH, and risk of lethal prostate cancer. 3) Determine optimal outpoints to refine the telomere biomarker for prognosis using both cohorts. 4) Evaluate whether prevalence of the refined telomere biomarker differs across age, race, and other patient characteristics. Differences in biomarker prevalence may inform the racial disparity in disease aggressiveness. We will extensively use the Pathology, Biostatistics, and Administrative Gores. We expect the telomere biomarker will be translated for clinical prognostic utility for prostate cancer in a trial in 5 years.
We expect that the telomere biomarker may identify prostate cancer patients who require enhanced treatment and surveillance, and importantly, patients who may not need intensive additional treatment, and possibly may not require treatment at all. Improved risk stratification allowing for individualized clinical management has the potential to increase the benefit to risk, and reduce healthcare costs for prostate cancer.
|Shrestha, Eva; White, James R; Yu, Shu-Han et al. (2018) Profiling the Urinary Microbiome in Men with Positive versus Negative Biopsies for Prostate Cancer. J Urol 199:161-171|
|Lu, Yunqi; Hu, Zhongyi; Mangala, Lingegowda S et al. (2018) MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels. Cancer Res 78:64-74|
|Das, Swadesh K; Pradhan, Anjan K; Bhoopathi, Praveen et al. (2018) The MDA-9/Syntenin/IGF1R/STAT3 Axis Directs Prostate Cancer Invasion. Cancer Res 78:2852-2863|
|Karnes, R Jeffrey; Choeurng, Voleak; Ross, Ashley E et al. (2018) Validation of a Genomic Risk Classifier to Predict Prostate Cancer-specific Mortality in Men with Adverse Pathologic Features. Eur Urol 73:168-175|
|Menezes, Mitchell E; Bhoopathi, Praveen; Pradhan, Anjan K et al. (2018) Role of MDA-7/IL-24 a Multifunction Protein in Human Diseases. Adv Cancer Res 138:143-182|
|Jiang, Wen; Ulmert, David; Simons, Brian W et al. (2018) The impact of age on radium-223 distribution and an evaluation of molecular imaging surrogates. Nucl Med Biol 62-63:1-8|
|Tsang, Sabrina H; Peisch, Samuel F; Rowan, Brendan et al. (2018) Association between Trichomonas vaginalis and prostate cancer mortality. Int J Cancer :|
|Baena-Del Valle, Javier A; Zheng, Qizhi; Esopi, David M et al. (2018) MYC drives overexpression of telomerase RNA (hTR/TERC) in prostate cancer. J Pathol 244:11-24|
|Martino, Thiago; Kudrolli, Tarana A; Kumar, Binod et al. (2018) The orally active pterocarpanquinone LQB-118 exhibits cytotoxicity in prostate cancer cell and tumor models through cellular redox stress. Prostate 78:140-151|
|Kaur, Harsimar B; Guedes, Liana B; Lu, Jiayun et al. (2018) Association of tumor-infiltrating T-cell density with molecular subtype, racial ancestry and clinical outcomes in prostate cancer. Mod Pathol 31:1539-1552|
Showing the most recent 10 out of 750 publications