B7-H6 as a Diagnostic Biomarker for Cervical Squamous Cell Carcinoma

Abstract

Background: B7-H6, a newly discovered member of the immunoglobulin superfamily, exerts antitumor effects by binding to NKP30 receptor on natural killer cells; it has important clinical implications. Cell surface ectodomain shedding of B7-H6 generates soluble B7-H6 (sB7-H6), which is highly expressed and serves as a valuable biomarker in multiple tumors, but the clinical significance and diagnostic value of B7-H6 in cervical squamous cell carcinoma (CSCC) remains unclear. Objective: To assess the expression and diagnostic value of B7-H6 in CSCC. Methods: In this study, 69 cervical specimens were analyzed for B7-H6 expression: 25 paired CSCC tissues were examined using quantitative real-time polymerase chain reaction, and 24 paraffin-embedded CSCC tissues and 20 normal tissues were analyzed immunohistochemically. Furthermore, plasma samples from 30 CSCC patients and 24 healthy controls were examined using ELISA. Results: B7-H6 mRNA and protein levels were significantly higher in CSCC tissues than in adjacent normal cervical tissues (p < 0.05). Immunohistochemical analysis revealed that high B7-H6 expression correlated with stromal invasion (p = 0.043), lymphovascular space involvement (p = 0.005), lymph node metastasis (p = 0.019), and International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.002). Moreover, ELISA results demonstrated that the sB7-H6 concentration in peripheral blood was higher in CSCC patients than in healthy controls (p < 0.0001). Notably, at the optimal cutoff point of 0.076 ng/mL, sB7-H6 showed 93.3% sensitivity and 62.5% specificity in the discrimination of CSCC patients from healthy controls. Conclusions: B7-H6 mRNA and protein levels are markedly increased in CSCC tissues and peripheral blood samples, and the B7-H6 level can be used as a biomarker for predicting the severity of CSCC disease and discriminating CSCC patients from healthy controls.

Keywords: B7-H6; NKP30; cervical squamous cell carcinoma; diagnostic biomarker; soluble B7-H6.