VSIG4 is highly expressed and correlated with poor prognosis of high-grade glioma patients

The high-grade glioma (HGG) remains as the greatest challenge for cancer management worldwide. Identification of novel therapeutics and diagnostic method is in urgent need. The V-set and immunoglobulin domain-containing protein 4 (VSIG4) is a complement receptor for C3b/iC3b and inhibits cytotoxic T lymphocytes activation, which may play important roles in glioma oncogenesis. In this study, we performed immunohistochemistry in tissue microarray to determine the expression of VSIG4 in malignant glioma and normal brain. We then applied univariate and multivariate analyses to evaluate the expression of VSIG4 and correlated with prognosis of glioma patients. We have shown that VSIG4 was significantly elevated in high-grade glioma compared with those of normal brain tissues (P<0.001). We have also found that high VSIG4 expression was an independent prognostic factor for a shorter progression-free survival (PFS) and overall survival (OS) in high-grade glioma patients [hazard ratio (HR) =1.786, P=0.011 and HR=2.199, P=0.001, respectively]. Patients with low VSIG4 expression had a significantly longer median OS and PFS than those with high VSIG4 expression. Subgroup analysis stratifying HGG patients by both VSIG4 expression and tumor grade further confirmed the independent prognostic role of VSIG4 in HGG patients, while no adjuvant radiotherapy, small extent of resection and higher tumor grade were other three independent risk factors for HGG poor prognosis. Similar findings were also obtained using data from Cancer Genome Atlas (TCGA). Together, our results support that VISG4 can be used as a prognostic factor and potentially an immunotherapeutic target for glioma.