Altered expression of NKX3.1 has significant prognostic value in gallbladder cancer

Abstract

Introduction: NKX3.1, an androgen regulated prostate specific transcription factor, inhibits prostate tumorigenesis. However, its role in GBC is not understood. We aimed to investigate NKX3.1 expression profile to define its role in GBC. Methods: We analyzed the expression of NKX3.1 in 52 GBC and 52 paired adjacent control samples at mRNA level through Real time RT-PCR and validated at protein level through Western blotting. The transcript level data was correlated with clinico-pathological parameters. Promoter hypermethylation was analyzed through methylation specific PCR (MSP). Results: NKX3.1 shows down regulation in 55.8%, up regulation in 25% whereas no change in 19.2% of samples. Its mRNA expression is significantly down regulated in late stage tumors (p =0.0103), in tumors with nodal metastasis (p =0 .0036) and in high grade tumors (p =0 .0173). Interestingly, NKX3.1 is significantly higher in male patients than female patients (p =0 .0057). Kaplan-Meyier analysis reveals prolonged median survival of patients with higher level of NKX3.1 expression compared with patients having low or no change in expression. Conclusion: Our findings suggest that loss or lower expression of NKX3.1 may be a critical in determining the phenotype of GBC. Its expression profile may serve as positive prognostic marker for GBC. © 2019 Elsevier Inc.