The B7-H4 coregulatory molecule is a member of the B7 family of molecules, which play a central role in the regulation of antigen-specific T cell-mediated immune responses. B7-H4, also referred to as B7x or B7S1, is a ligand within the B7 family that has been implicated as a negative regulator of T cell-mediated immunity. Robust B7-H4 protein expression is primarily restricted to activated T cells, B cells, dendritic cells, and monocytes.

Nemo-like kinase (NLK), a serine/threonine protein kinase, has been implicated in tumor development and progression, and plays an important role in diverse signaling pathways by phosphorylating a variety of transcription factors. Recent studies demonstrated that altered expression of NLK was observed in various types of human cancers. However, the clinical significance of NLK expression in gallbladder cancer (GBC) remains largely unknown. In this study, we focused on the clinical significance of NLK in GBC, and found that nuclear NLK protein overexpression was frequently detected in GBC tissues. The overexpression of NLK was significantly correlated with histological grade, TNM stage, and perineural invasion. The results of Kaplan-Meier analysis indicated that a high expression level of NLK resulted in a significantly poorer prognosis of GBC patients (P = 0.002). Furthermore, multivariate Cox regression analysis showed that high NLK expression was an independent prognostic factor for GBC patients (HR = 3.077). In conclusion, overexpression of NLK is closely related to progression of GBC, and NLK could be used as a potential prognostic marker for GBC patients.

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