Identification of tumor-agnostic biomarkers for predicting prostate cancer progression and biochemical recurrence.

Autor:	Lautert-Dutra W; Department of Genetics, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil., Melo CM; Department of Genetics, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil., Chaves LP; Department of Genetics, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil., Souza FC; Division of Urology, Department of Surgery and Anatomy, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil., Crozier C; Diagnostic Development, Ontario Institute for Cancer Research, Toronto, ON, Canada., Sundby AE; Diagnostic Development, Ontario Institute for Cancer Research, Toronto, ON, Canada., Woroszchuk E; Diagnostic Development, Ontario Institute for Cancer Research, Toronto, ON, Canada., Saggioro FP; Department of Pathology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil., Avante FS; Division of Urology, Department of Surgery and Anatomy, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil., Dos Reis RB; Division of Urology, Department of Surgery and Anatomy, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil., Squire JA; Department of Genetics, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada., Bayani J; Diagnostic Development, Ontario Institute for Cancer Research, Toronto, ON, Canada.; Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2023 Oct 26; Vol. 13, pp. 1280943. Date of Electronic Publication: 2023 Oct 26 (Print Publication: 2023).
DOI:	10.3389/fonc.2023.1280943
Abstrakt:	The diverse clinical outcomes of prostate cancer have led to the development of gene signature assays predicting disease progression. Improved prostate cancer progression biomarkers are needed as current RNA biomarker tests have varying success for intermediate prostate cancer. Interest grows in universal gene signatures for invasive carcinoma progression. Early breast and prostate cancers share characteristics, including hormone dependence and BRCA1/2 mutations. Given the similarities in the pathobiology of breast and prostate cancer, we utilized the NanoString BC360 panel, comprising the validated PAM50 classifier and pathway-specific signatures associated with general tumor progression as well as breast cancer-specific classifiers. This retrospective cohort of primary prostate cancers ( n =53) was stratified according to biochemical recurrence (BCR) status and the CAPRA-S to identify genes related to high-risk disease. Two public cohort (TCGA-PRAD and GSE54460) were used to validate the results. Expression profiling of our cohort uncovered associations between PIP and INHBA with BCR and high CAPRA-S score, as well as associations between VCAN , SFRP2 , and THBS4 and BCR. Despite low levels of the ESR1 gene compared to AR , we found strong expression of the ER signaling signature, suggesting that BCR may be driven by ER-mediated pathways. Kaplan-Meier and univariate Cox proportional hazards regression analysis indicated the expression of ESR1 , PGR , VCAN , and SFRP2 could predict the occurrence of relapse events. This is in keeping with the pathways represented by these genes which contribute to angiogenesis and the epithelial-mesenchymal transition. It is likely that VCAN works by activating the stroma and remodeling the tumor microenvironment. Additionally, SFRP2 overexpression has been associated with increased tumor size and reduced survival rates in breast cancer and among prostate cancer patients who experienced BCR. ESR1 influences disease progression by activating stroma, stimulating stem/progenitor prostate cancer, and inducing TGF-β. Estrogen signaling may therefore serve as a surrogate to AR signaling during progression and in hormone-refractory disease, particularly in prostate cancer patients with stromal-rich tumors. Collectively, the use of agnostic biomarkers developed for breast cancer stratification has facilitated a precise clinical classification of patients undergoing radical prostatectomy and highlighted the therapeutic potential of targeting estrogen signaling in prostate cancer. Competing Interests: JB has the patent application “A Molecular Classifier for Personalized Risk Stratification for Patients with Prostate Cancer” under consideration. Status: PCT, Filing date: June 18, 2021, International Application No.: PCT/CA2021/050837, PCT Application Title: Molecular Classifiers for Prostate Cancer. Previous US Provisional Status: Filing Date: June 18, 2020, US Provisional Patent No. 63/040.692, US Provisional Application Title: Use of Molecular Classifiers to Diagnose, Treat, and Prognose Prostate Cancer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. (Copyright © 2023 Lautert-Dutra, Melo, Chaves, Souza, Crozier, Sundby, Woroszchuk, Saggioro, Avante, dos Reis, Squire and Bayani.)
Databáze:	MEDLINE
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