Abstract
A clinical dilemma in the management of prostate cancer (PCa) is to distinguish men with aggressive disease who need definitive treatment from men who may not require immediate intervention. Accurate prediction of disease behavior is critical because radical treatment is associated with high morbidity. Here, we highlight the cancer/testis antigens (CTAs) as potential PCa biomarkers. The CTAs are a group of proteins that are typically restricted to the testis in the normal adult but are aberrantly expressed in several types of cancers. Interestingly, >90% of CTAs are predicted to belong to the realm of intrinsically disordered proteins (IDPs), which do not have unique structures and exist as highly dynamic conformational ensembles, but are known to play important roles in several biological processes. Using prostate-associated gene 4 (PAGE4) as an example of a disordered CTA, we highlight how IDP conformational dynamics may regulate phenotypic heterogeneity in PCa cells, and how it may be exploited both as a potential biomarker as well as a promising therapeutic target in PCa. We also discuss how in addition to intrinsic disorder and post-translational modifications, structural and functional variability induced in the CTAs by alternate splicing represents an important feature that might have different roles in different cancers. Although it is clear that significant additional work needs to be done in the outlined direction, this novel concept emphasizing (multi)functionality as an important trait in selecting a biomarker underscoring the theranostic potential of CTAs that is latent in their structure (or, more appropriately, the lack thereof), and casts them as next generation or “smart” biomarker candidates.
Highlights
Prostate cancer (PCa) is one of the most prevalent forms of cancer in older men over the age of 50
Notwithstanding the slight disparity in the cancer/testis antigens (CTAs) that appear to discriminate disease progression, this study further demonstrated the potential of the CTAs as PCa biomarkers [51] using achieved samples
The authors evaluated prostate-associated gene 4 (PAGE4) as a biomarker to discern symptomatic and asymptomatic benign prostate hypertrophy (BPH), it is plausible that serum PAGE4 levels could discern PCa from normal and substitute for prostate-specific antigen (PSA) given that, in the adult human male, PAGE4 is remarkably prostate-specific marker and is undetectable in the normal adult prostate [108,147]
Summary
Prostate cancer (PCa) is one of the most prevalent forms of cancer in older men over the age of 50. It is important for physicians and patients to know the likelihood of disease progression following radical prostatectomy Considered together, it follows that there is a critical need to identify reliable biomarkers that may be used for better diagnosis as well as to distinguish most of the low-GS tumors that will remain indolent from the few that are truly aggressive to better treat and manage PCa. The advent of advanced technologies and sophisticated bioinformatics algorithms has fueled the discovery of novel biomarkers that include serum-, urine- and tissue-based assays that may supplement PSA testing, or even replace it over time (reviewed in [20,21,22,23,24,25,26,27,28]). Notwithstanding the slight disparity in the CTAs that appear to discriminate disease progression, this study further demonstrated the potential of the CTAs as PCa biomarkers [51] using achieved samples
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