Cancer/Testis Antigens: “Smart” Biomarkers for Diagnosis and Prognosis of Prostate and Other Cancers

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.

MAGEA1 inhibits the expression of BORIS via increased promoter methylation

“…Cancer testis antigens (CTAs) have been extensively studied in a variety of cancers of diverse histological origin and germinal cells (Lim et al, 2012;Zajac et al, 2017). However, the majority of these studies focused on the correlative expression data and/or on evaluating their immunotherapeutic targeting or tumor biomarker values, with limited studies on their gene expression regulation and even fewer on their cellular function in cancer cells (Lim et al, 2012;Kulkarni and Uversky, 2017).…”

Hypomethylation‐activated cancer‐testis gene SPANXC promotes cell metastasis in lung adenocarcinoma

“…The procedure of germ cell formation and tumorigenesis has significant similarities, involving cell immortalization, migration and invasion, induction of meiosis . CT genes have been known as prospective cancer markers and objectives for therapy . The activation of CT gene expression in various types of tumours was observed .…”

“…7 CT genes have been known as prospective cancer markers and objectives for therapy. 20 The activation of CT gene expression in various types of tumours was observed. 21,22 Previous study found that the activation frequency of CT gene is much changeful depending on cancer type, the melanomas, the liver and lung cancers could show a high rate of recurrence.…”

Cancer/Testis Antigens Differentially Expressed in Prostate Cancer: Potential New Biomarkers and Targets for Immunotherapies

“…CTAs by definition are normally expressed in testis and other developmentally regulated tissues (e.g., placenta) but are aberrantly expressed in many types of cancers [19]. This unique pattern of expression makes these genes attractive candidates as biomarkers and, together with their immunogenic capacity, also good targets for the development of cancer immunotherapy [20][21][22]. The aberrant expression of CTAs in different cancer types is associated with phenotypic changes that confer cancer cells added advantages for proliferation and survival [23,24].…”