Advances in Biomedical and Health Sciences (Jan 2022)
Expression of tissue PSA in breast cancer is associated with less aggressive disease and lower chance of tumor relapse
Abstract
Background: Human kallikrein 3 (hK3), also known as Prostatic specific antigen (PSA), was considered as one of the most useful markers for the detection as well as management of prostate cancer. While PSA was thought to be a prostatic tissue-specific protein, many reports suggest the presence of extraprostatic PSA in different tissues, including the breast. Few reports showed PSA immunoreactivity in breast cancer tissues and suggest a favorable prognostic role of PSA in breast cancer. However, most of those studies were not conclusive or restricted to small scale studies limiting their clinical significance. Methods: We used a bioinformatical approach to investigate the association between tissue PSA expression levels and different clinicopathological parameters in breast cancer using different publicly available databases. Further validation was done using our patient cohort of 40 surgical breast samples obtained from patients attending Al Kadhemyia Teaching Hospital – Iraq. Results: Using a cohort of 593 breast lesion samples extracted from the TCGA database using the ONCOMINE database, our results showed no significant upregulation of PSA mRNA levels in breast cancer samples compared to healthy tissue (P = 0.1). The same trend was also observed in our patient cohort with positive immunoreactivity in 50% (5 samples) of benign lesions compared to 36.66% (11 samples) in breast cancer samples. In addition, investigating the correlation between mRNA PSA expression and different clinicopathological parameters using the Breast Cancer Gene-Expression Miner v4.0 database and ONCOMINE databases, revealed a significant association between PSA expression and tumor grade (P = 0.0001), breast cancer subtype (P < 0.0001), in addition to early-stage disease presented as smaller tumor size and absence of LN involvement. The same trend confirmed with our patient cohort. Moreover, our analysis using KM plotter (4000 breast cancer samples) showed a significant association between higher PSA mRNA levels and favorable patient outcomes presented as prolonged relapse-free survival (RFS) (P < 0.0001). Conclusions: Our results clearly demonstrate the possibility of using tissue mRNA and protein levels of PSA as a marker to identify patients with a favorable outcome and lower risk of tumor recurrence. Our results also highlight the need for more efforts to investigate the biological role of PSA in breast cancer.
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