A recent study published in the Journal of Cancer Research and Clinical Oncology explored genetic predictors of prostate cancer progression to help identify its clinical outcomes. Conducted by researchers from the D'Or Institute for Research and Education (IDOR), the University of São Paulo (USP), and the São Paulo Cancer Institute (ICESP), the study focused on the role of the androgen receptor (AR), its variant AR-V7, and the p160 gene family.
Prostate cancer: a complex and deadly disease
Prostate cancer is one of the leading causes of death among men, claiming more than 40 lives daily in Brazil. One of its biggest challenges is predicting which cases will become more aggressive, as the disease varies greatly between individuals. To uncover genetic clues that could help in early detection of high-risk cases, researchers focused on specific genes commonly associated with prostate cancer progression.
Investigating key genes
The study analyzed five key genes:
AR (androgen receptor) – Plays a crucial role in male traits and prostate cancer progression.
AR-V7 (a variant of AR) – Linked to castration-resistant prostate cancer (CRPC), which continues to progress despite androgen-suppressing treatments.
p160 gene family (SRC-1, SRC-2, and SRC-3) – Co-activators of AR that influence cancer aggressiveness.
The research involved 155 patients who underwent radical prostatectomy (prostate removal) between 1994 and 2012, as well as tissue samples from 11 healthy individuals as a control group. Using qPCR, a technique that amplifies and quantifies DNA or RNA, the scientists measured gene expression levels in the collected tissue samples. Their goal was to investigate the relationship between genetic profiles and clinical characteristics, such as cancer recurrence and progression to CRPC.
Linking gene expression to clinical outcomes
The results showed that, except for SRC-1, all analyzed genes had higher activation levels in cancer patients compared to the control group. While SRC-1 did not reach statistical significance, its average expression was still higher in cancer patients, and the study suggested its relevance in metastatic cancer progression, indicating some potential as a prognostic factor.
Another key finding was that AR gene expression was not directly linked to the expression of its auxiliary genes (SRC-1, SRC-2, and SRC-3) or to AR-V7. However, AR-V7 was strongly associated with the p160 family genes, suggesting that AR-V7's ability to help prostate cancer cells resist hormone therapy depends on these auxiliary genes, especially SRC-3.
Additionally, SRC-2 and SRC-3 were significantly linked to high-risk prostate cancer, while excessive AR activation was associated with a 73.2% higher risk of early recurrence. AR-V7 expression also showed a 62.1% increase in early recurrence risk. These findings underscore the importance of androgen signaling in prostate cancer recurrence and tumor development.
The study suggests that these genes could serve as potential prognostic biomarkers for prostate cancer. While SRC-1 showed distinct activation in metastatic cases, SRC-2 and SRC-3 had expression changes that may help identify more aggressive malignancies.
The authors emphasize that these correlations require further investigation, particularly the association between SRC-3 and AR-V7, which could provide deeper insights into the role of p160 family proteins in CRPC development. These promising findings pave the way for future studies on the role of androgen-related genes in prostate cancer prognosis, contributing to advancements in personalized treatment approaches for the disease.
