Novel immune checkpoint CD112 and CD112R can be potential prognosis biomarker in immune infiltration of cervical cancer

CD112 (encoded by the gene NECTIN2) and CD112R (encoded by the gene PVRIG) are new immune checkpoints. They are expressed in both PD-L1-negative and PD-L1-positive tumour tissues. However, their expression pattern and biological significance in cervical cancer remain unknown. In this study, we obtained the expression of CD112/CD112R and clinical prognosis in cervical cancer via multiple databases. The results were further investigated using real-time quantitative PCR (RT-qPCR) in cytology specimens and immunohistochemical staining (IHC) in tissue microarray (TMA). Furthermore, Receiver-Operating-Characteristics (ROC) analysis and Kaplan-Meier Cox regression were used to assess the clinical significance and prognosis of CD112/CD112R in cervical cancer patients. CD112 and CD112R were highly increased in almost all tumours, including cervical cancer. RT-qPCR and IHC results were consistent with the above. Also, NECTIN2 (CD112) mRNA expression increased with the development of cervical lesions. In addition, we found that CD112 mRNA expression had a high AUC of 0.849, and an optimal cut-off was 0.465 to predict more than high-grade cervical lesions (CIN2+). CD112 expression is an independent prognostic factor. Furthermore, over-expression of CD112 was significantly related to poor overall survival (OS) (HR = 2.97, 95%CI = 1.05–8.44) and disease-free survival (DFS) (HR = 3.15, 95% CI = 1.15–8.61). However, over-expression of CD112R was associated with poor OS (HR = 2.87, 95% CI = 1.01–8.14), but not DFS. The results demonstrated that CD112 and CD112R expression computationally inferred with immune cell infiltration in cervical cancer, but not with other immune checkpoints. This study demonstrated that CD112/CD112R expression increased in cervical cancer. Together, these data position CD112 as a prognostic and immune-association biomarker, and suggest the CD112/CD112R axis merits further functional and therapeutic investigation rather than immediate designation as a validated immunotherapy target.