HLA-G 14 bp insertion/deletion polymorphism is a prognostic factor for non-small-cell lung cancer

Abstract

Objective To study the correlation between human leucocyte antigen-G (HLA-G) 14 bp insertion/deletion (I/D) polymorphism and susceptibility to non-small cell lung cancer (NSCLC) as well as poor prognosis in NSCLC. Methods A total of 113 patients with NSCLC and 150 age- and sex-matched healthy subjects were genotyped by PCR to analyze the HLA-G 14 bp insertion/deletion polymorphism in them. Epidermal growth factor receptor (EGFR) gene mutation in patients with NSCLC was detected by using amplification refractory mutation system (AMRS). Expression of HLA-G in NSCLC tissues was detected with immunohistochemistry. All patients with NSCLS were followed up to collect survival data, which were further analyzed with Kaplan-Meier method. Results The frequency of HLA-G 14 bp D/D genotype was significantly higher in the patients with NSCLC than that in the healthy subjects (χ2=3.907, P=0.048, OR=1.66). Among the patients with NSCLC, HLA-G 14 bp I/I genotype carriers had a shorter overall survival time as compared with that of HLA-G 14 bp I/D or HLA-G 14 bp D/D genotype carriers (P=0.005). Patients who received chemotherapy or radiation had significantly shorter survival time than those received EGFR-targeted therapy (P=0.001). Among patients who were positive for EGFR mutation, HLA-G 14 bp D/D genotype carriers had longer survival time than those carrying HLA-G 14 bp I/I or HLA-G 14 bp I/D genotype (P=0.041). The expression of HLA-G was closely correlated with HLA-G 14 bp polymorphism in patients with NSCLC (P=0.001). Conclusion These data, reported for the first time, indicates that HLA-G 14 bp polymorphism might be a genetic factor related to the susceptibility to NSCLC and associated with survival in patient with NSCLC after excluding the interference of molecular targeted agents. Key words: HLA-G; Polymorphism; Non-small-cell lung cancer; Targeted therapy