Chemerin and Chemokine-like Receptor 1 Expression in Ovarian Cancer Associates with Proteins Involved in Estrogen Signaling

Chemerin, a pleiotropic adipokine coded by the RARRES2 gene, has been reported to affect the pathophysiology of various cancer entities. To further approach the role of this adipokine in ovarian cancer (OC), intratumoral protein levels of chemerin and its receptor chemokine-like receptor 1 (CMKLR1) were examined by immunohistochemistry analyzing tissue microarrays with tumor samples from 208 OC patients. Since chemerin has been reported to affect the female reproductive system, associations with proteins involved in steroid hormone signaling were analyzed. Additionally, correlations with ovarian cancer markers, cancer-related proteins, and survival of OC patients were examined. A positive correlation of chemerin and CMKLR1 protein levels in OC (Spearman's rho = 0.6, p < 0.0001) was observed. Chemerin staining intensity was strongly associated with the expression of progesterone receptor (PR) (Spearman ' s rho = 0.79, p < 0.0001). Both chemerin and CMKLR1 proteins positively correlated with estrogen receptor beta (ER beta) and estrogen-related receptors. Neither chemerin nor the CMKLR1 protein level was associated with the survival of OC patients. At the mRNA level, in silico analysis revealed low RARRES2 and high CMKLR1 expression associated with longer overall survival. The results of our correlation analyses suggested the previously reported interaction of chemerin and estrogen signaling to be present in OC tissue. Further studies are needed to elucidate to which extent this interaction might affect OC development and progression.

Automated summary

Chemerin, a pleiotropic adipokine coded by the RARRES2 gene, and its receptor CMKLR1 were found to be positively correlated in ovarian cancer. Chemerin staining intensity was also strongly associated with the expression of progesterone receptor. Both chemerin and CMKLR1 proteins showed positive correlations with estrogen receptor beta and estrogen-related receptors. However, neither chemerin nor CMKLR1 protein levels were associated with the survival of ovarian cancer patients. Further studies are needed to understand the extent to which this interaction affects ovarian cancer development and progression.