Dynamic Soluble IL-6R/Soluble gp130 Ratio as a Potential Indicator for the Prostate Malignancy Phenotype-A Multicenter Case-Control Study

Abstract

Objective: Prostate tumors, if prostate cancer or adenoma, represent a major public health challenge. Progress in research on inflammation has revealed a connection between inflammation, immunity, and cancer. In this context, this study aimed to find IL-6 signaling systemic abnormalities in the inflammatory tumor microenvironment.

Material and methods: This study was case-controlled, multicentered, and included 86 patients, 43 diagnosed with BPH and 43 diagnosed with PCa, between January 2019 and January 2020. The study group was homogenous and the studied parameters were IL-6 complex (IL-6, soluble receptor IL-6R, soluble glycoprotein gp130), acute phase proteins (C reactive protein-CRP, acid alpha1 glycoprotein-AGPA, ferritin, albumin, transferrin), and oxidative stress-associated variables (malondialdehyde-MDA, carbonylated protein-PCO, 8-hydroxy-deoxy guanosine-8-OHdG, total antioxidant status-bTAS).

Results: The inflammatory microenvironment determined IL-6 signaling alterations (over-regulation of sIL-6R and suppression of sgp130 in PCa versus BPH), changes in acute phase reaction markers (increased serum levels of CRP, AGPA, ferritin, and decreased serum levels of albumin, transferrin) that were much more evident in PCa compared to BPH, an imbalance between macromolecular oxidative damage (MDA, PCO, 8-OHdG) and endogenous antioxidants (TAS) that was more accentuated in PCa compared with BPH, and a representative association between the sIL-6R/sgp130 ratio and inflammatory/oxidative stress-related factors only in PCa patients.

Conclusions: Our study reconfirms the anterior concept that IL-6 promotes prostatic tumorigenesis. In this study, we first demonstrated that a high sIL-6R/sgp130 ratio facilitates prostate malignancy.

Keywords: IL-6 signaling; acute phase reaction; inflammation; microenvironment; oxidative stress; prostate tumors.

Figure 1

Schematic illustration of IL-6 signaling IL-interleukin; IL-6R-IL6 receptor; mIL-6R-membranar-IL-6R; gp130-glycoprotein; sIL-6R-soluble IL-6R; sgp130-soluble; gp130; jak/STAT-Janus kinase/signal transducers and activators of transcription; MAPK-Mitogen-activated protein kinase; and PI3K- Phosphoinositide 3-kinase.