Abstract
Simple SummaryProstate tumors are heterogeneous with unpredictable outcomes, ranging from harmless to aggressive, metastatic and deadly disease. Current diagnostic methods have limited ability to predict disease aggressiveness. New biomarkers are urgently needed to improve risk stratification, preferably involving non-invasive procedures. The aim of this prospective study was to assess the prognostic value of the inflammation markers S100A9 and S100A12 together with the monocyte count in blood samples from a cohort of 121 prostate cancer patients. We show that high monocyte count and high mRNA levels of S100A9, S100A12 are associated with poor outcome in patients with metastases at diagnosis. Our results suggest that analysis of these factors in blood could identify patients who are in direct need of additional treatment to conventional androgen deprivation therapy (ADT).Increasing evidence indicates calcium-binding S100 protein involvement in inflammation and tumor progression. In this prospective study, we evaluated the mRNA levels of two members of this family, S100A9 and S100A12, in peripheral blood mononuclear cells (PBMCs) in a cohort of 121 prostate cancer patients using RT-PCR. Furthermore, monocyte count was determined by flow cytometry. By stratifying patients into different risk groups, according to TNM stage, Gleason score and PSA concentration at diagnosis, expression of S100A9 and S100A12 was found to be significantly higher in patients with metastases compared to patients without clinically detectable metastases. In line with this, we observed that the protein levels of S100A9 and S100A12 in plasma were higher in patients with advanced disease. Importantly, in patients with metastases at diagnosis, high monocyte count and high levels of S100A9 and S100A12 were significantly associated with short progression free survival (PFS) after androgen deprivation therapy (ADT). High monocyte count and S100A9 levels were also associated with short cancer-specific survival, with monocyte count providing independent prognostic information. These findings indicate that circulating levels of monocytes, as well as S100A9 and S100A12, could be biomarkers for metastatic prostate cancer associated with particularly poor prognosis.
Highlights
Prostate tumors are heterogeneous and with an unpredictable outcome, ranging from tumors causing no symptoms to aggressive, metastatic and deadly disease
We show that mRNA expression of both S100A9 and S100A12 was positively correlated with monocyte count, suggesting that a population of monocytes could be one source of these proteins in peripheral blood mononuclear cells (PBMCs)
We have previously shown that heme oxygenase-1 (HO-1)-positive macrophages are abundant in prostate bone metastases and at higher levels than in primary tumors [47]
Summary
Prostate tumors are heterogeneous and with an unpredictable outcome, ranging from tumors causing no symptoms to aggressive, metastatic and deadly disease. Previous studies have shown that systemic inflammation, measured by combining C-reactive protein and albumin, is associated with excess risk of death from prostate cancer [8] This suggests that inflammatory cells and inflammatory markers in the circulation could have prognostic value. Studies of mRNA expression signatures in whole blood from patients with castration resistant prostate cancer (CRPC) have indicated that a dysfunctional immune system might be a key factor in determining poor prognosis [25,26,27] In this prospective study, the aim was to evaluate the level distribution of S100A9 and S100A12 in peripheral blood mononuclear cells (PBMCs) and its prognostic value in prostate cancer patients. We show that high expression of S100A9 and S100A12 and a high monocyte count are associated with poor outcome in patients with metastases at diagnosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
