Abstract
Although many patients are cured from prostate cancer (PCa) by surgery only, there are still patients who will experience rising prostate-specific antigen (PSA) levels after surgery, a condition known as biochemical recurrence (BCR). Novel protein prognostic markers in PCa tissue might enable finding better treatment for those patients experiencing BCR with a high chance of metastasis. In this study, we aimed to identify altered proteins in prostate cancer tissue, and to evaluate their potential role as prognostic markers. We used two proteomics strategies to analyse 34 prostate tumours (PCa) and 33 normal adjacent prostate (NAP) tissues. An independent cohort of 481 samples was used to evaluate the expression of three proteins: AGR2, FASN and LOX5 as prognostic markers of the disease. Tissue microarray immunohistochemical staining indicated that a low percentage of positive tumour cells for AGR2 (HR (95% CI) = 0.61 (0.43-0.93)), and a low percentage of positive tumour cells for LOX5 expression (HR (95% CI) = 2.53 (1.23-5.22)) are predictors of BCR after RP. In contrast, FASN expression had no prognostic value for PCa.
Highlights
Prostate cancer (PCa) remains to date the most commonly diagnosed cancer in men in the Western world [1]
Many patients are cured from this disease after radical prostatectomy (RP) [2], one third of patients will show an increment in serum prostate-specific antigen (PSA) levels - known as biochemical recurrence (BCR)-[3]
anterior gradient protein 2 (AGR2) is a predictor of biochemical recurrence after performing Tissue Microarray (TMA) immunostaining in the Evaluation set (Figure 4), confirming previous reports for this protein as biomarker for prostate cancer (PCa) [13,14,15]
Summary
Prostate cancer (PCa) remains to date the most commonly diagnosed cancer in men in the Western world [1]. Many patients are cured from this disease after radical prostatectomy (RP) [2], one third of patients will show an increment in serum PSA levels - known as biochemical recurrence (BCR)-[3]. For those patients, more frequent follow-up and adjuvant therapies are often required to limit progression of the disease [3, 4]. There is a high need for robust molecular markers that can distinguish indolent cases of PCa from those that will recur after initial treatment [3, 4] Small molecules, such as metabolites and lipids, have been associated with the progression of different types of cancer, including PCa [5]. These findings suggest that the AA pathway might play an important role in www.oncotarget.com
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