Immunoregulatory protein V-set and immunoglobulin domain-containing 4 is overexpressed in patients with endometriosis

V-set and immunoglobulin domain-containing 4 (VSIG4) is a potent negative regulator of T-cell responses and is suggested to regulate antitumor immunity. This study investigates whether VSIG4 is significantly expressed in endometriosis patients and the association between VSIG4 levels and serum cancer antigen (CA)-125 levels, VSIG4 levels and endometriosis severity.

Tumor tissues and peripheral blood samples were obtained during surgery from 42 endometriotic cyst and 21 nonendometriotic tumor patients. The levels of VSIG4 mRNA, VSIG4 protein expression in tumor tissue and serum soluble VSIG4 concentration were compared between the two groups. After dividing the cohort using the optimized cut-off values obtained by receiver operating characteristic curve analysis, we examined the association between VSIG4 levels and serum CA-125 levels, VSIG4 levels and the factors indicating endometriosis severity.

The expressions of VSIG4 mRNA, VSIG4 protein and serum VSIG4 concentration were significantly increased in the endometriotic cyst group compared with the control group (P = 0.001, 0.002 and 0.049, respectively). The optimized VSIG4 cut-off values for endometriosis prediction were 0.71, 0.32 and 144.37 pg/mL, respectively. After cohort division using these values, high VSIG4 levels group showed significantly elevated CA-125 compared with low VSIG4 level group (P = 0.010, 0.043 and 0.039, respectively). There was no association between VSIG4 levels and the factors indicating endometriosis severity.

The expression of VSIG4 in endometriosis patients is increased compared with nonendometriotic tumor patients, and higher VSIG4 levels are significantly associated with higher serum CA-125 levels. VSIG4 may be importantly involved in the immunological alteration of endometriosis.