Tissue proteomics outlines AGR2 AND LOX5 as markers for biochemical recurrence of prostate cancer

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.

Differential tissue expression of extracellular vesicle‐derived proteins in prostate cancer

“…The FASN TMA analyses have recently been published as part of the tissue proteomics study and revealed that expression among the PCa samples was higher in GS < 7 and GS = 7 (49.0% and 34.6%, respectively) than in GS > 7 (5.4%). This is in agreement with previous studies …”

“…From this list, 10 proteins were identified as higher expressed in PCa‐derived EVs of which expression of 3 proteins (XPO1, FASN, and PDCD6IP) were further analyzed for EV and tissue expression. For a first validation, we compared the 263 proteins to a shotgun mass spectrometry database recently published which 34 PCa (n = 22 GS 6, n = 12 GS≥ 7) and 33 NAP tissues were compared using label‐free quantification . In this database, a total of 2865 proteins were identified from which 798 proteins were statistically significant differentially expressed between normal prostate and PCa (FDR < 0.01).…”

“…A, Overlap of proteins between the discovery set of extracellular vesicle‐associated proteins (n = 263) and the proteins differentially expressed between prostate cancer (PCa) and normal adjacent prostate (NAP) tissue (n = 798) . B, Protein expression (LOG10 normalized) of XPO1 and PDCD6IP in NAP (n = 33) and PCa tissue (n = 34) and in C, Gleason score < 7 (n = 22) vs Gleason score ≥ 7 (n = 12) [Color figure can be viewed at wileyonlinelibrary.com]…”

“…Protein fractions from tissue RNA isolations with RNA‐Bee of 67 PCa tissue samples (33 NAP and 34 PCa) were selected and stored at −80°C as described in Rodriguez et al Samples were thawed and 50 µL precipitated with cold acetone and microcentrifugation. After 10 minutes, the supernatant was removed and the pellet washed twice with cold acetone.…”

“…The objective of this study was to investigate whether the PCa EV‐associated expression could be reproduced in tissue analyses of larger cohorts of patients. Result for FASN has been published previously …”