The interplay of growth differentiation factor 15 (GDF15) expression and M2 macrophages during prostate carcinogenesis

Authors

Sudha M. Sadasivan, Henry Ford HealthFollow
Yalei Chen, Henry Ford HealthFollow
Nilesh S. Gupta, Henry Ford HealthFollow
Xiaoxia Han, Henry Ford HealthFollow
Kevin R. Bobbit, Henry Ford HealthFollow
Dhananjay A. Chitale, Henry Ford HealthFollow
Sean R. Williamson, Henry Ford HealthFollow
Andrew G. Rundle
Deliang Tang
Benjamin A. Rybicki, Henry Ford HealthFollow

Recommended Citation

Sadasivan SM, Chen Y, Gupta NS, Han X, Bobbitt KR, Chitale DA, Williamson SR, Rundle AG, Tang D, and Rybicki BA. The interplay of GDF15 (growth differentiation factor 15) expression and M2 macrophages during prostate carcinogenesis. Carcinogenesis 2020.

Document Type

Article

Publication Date

8-12-2020

Publication Title

Carcinogenesis

Abstract

M2 (tumor-supportive) macrophages may upregulate growth differentiation factor 15 (GDF15), which is highly expressed in prostate tumors, but the combined utility of these markers as prognostic biomarkers are unclear. We retrospectively studied 90 prostate cancer cases that underwent radical prostatectomy as their primary treatment and were followed for biochemical recurrence (BCR). These cases also had a benign prostate biopsy at least 1 year or more before their prostate cancer surgery. Using computer algorithms to analyze digitalized immunohistochemically stained slides, GDF15 expression and the presence of M2 macrophages based on the relative density of CD204- and CD68-positive macrophages were measured in prostate: (i) benign biopsy, (ii) cancer and (iii) tumor-adjacent benign (TAB) tissue. Both M2 macrophages (P = 0.0004) and GDF15 (P < 0.0001) showed significant inter-region expression differences. Based on a Cox proportional hazards model, GDF15 expression was not associated with BCR but, in men where GDF15 expression differences between cancer and TAB were highest, the risk of BCR was significantly reduced (hazard ratio = 0.26; 95% confidence interval = 0.09-0.94). In addition, cases with high levels of M2 macrophages in prostate cancer had almost a 5-fold increased risk of BCR (P = 0.01). Expression of GDF15 in prostate TAB was associated with M2 macrophage levels in both prostate cancer and TAB and appeared to moderate M2-macrophage-associated BCR risk. In summary, the relationship of GDF15 expression and CD204-positive M2 macrophage levels is different in a prostate tumor environment compared with an earlier benign biopsy and, collectively, these markers may predict aggressive disease.

PubMed ID

32614434

ePublication

ePub ahead of print

Volume

41

Issue

8

First Page

1074

Last Page

1082