Correlation Of The PD-l1 Polymorphisms And SPD-l1 To Esophageal Squamous Cell Carcinoma In China

Objective : Tumor immune evasion plays an important role in the physiopathological process of tumor genesis,invasion and metastasis. It is well established that engagement of PD-1/PD-L1 delivers a potent coinhibitory signal to T cells, resulting in T cell exhaustion and dysfunction timely to prevent excessive immune injury and maintain self-balance of the immune system. It has been reported that PD-1/PD-L1 pathway plays a critical role in tumor immunity, autoimmune and chronic viral infectious diseases. In this study, firstly, we selected 3 single nucleiotides polymorphisms (SNPs) located in the PD-L1 gene as the gene markers. By using the case-control association analysis, we will investigate the relationship between ESCC and the single SNP and the haplotypes which consist of these SNPs. Secondly, we revealed the relationship between the expression of sPD-L1 and the occurrence and development of ESCC in order to provide a new biomarker for the treatment and a new early diagnosis of ESCC.Methods:In the present study, on one hand, to analyze the relationship between PD-L1 gene polymorphism and susceptibility of ESCC, Allele Specific amplification(ASA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RPLP) was used for the polymorphism of PD-L1 gene in blood DNA from ESCC patients and normal blood samples. On the other hand, to evaluate the biological significance of sPD-L1 in the patients with ESCC, the serum from ESCC patients were collected and detected by the established sPD-L1 ELISA.Results: (1). In this study, we genotyped three single nucleotide polymorphisms (SNP1, rs2297136 A>G; SNP2, rs4143815 C>G; SNP3, rs74589371 A>C) located within the PD-L1 gene. Statistically significant differences were found for rs4143815 C>G and the recessive model were accepted as the best inheritance model. We also showed that the haplotype-G C A composed of three SNPs exhibited significant association with the disease (P =0.029), this haplotype was more frequently observed in cases than in controls (OR: 0.22, 95 % CI: 0.06– 0.84).(2). ELISA visualization show that soluble PD-L1 existed in ESCC patients and healthy person's sera. The serum sPD-L1 levels in patients with ESCC were significantly higher than those in healthy controls (P < 0.001). The soluble expression of PD-L1 was closely correlated to the length of the ESCC (P < 0. 05).Conclusion: (1). The rs4143815 C>G in PD-L1 gene are significantly associated with ESCC and Lymph node metastasis in Han Chinese patients. One single haplotype composed of three markers is associated with ESCC. These results suggest that a common ESCC predisposing variant in the PD-L1 gene might play an important predisposing role in the pathogenesis of ESCC. Our study provides further evidence that the PD-L1 gene is involved in the susceptibility to ESCC in the Han Chinese population.(2). The soluble PD-L1 expression was increased in ESCC patients'serum, and closely correlated to the length of the tumor. The soluble PD-L1 may be a new marker of diagnosis for ESCC. Measurement of serum PD-L1, not only provide useful information for distinctive diagnosis of ESCC, but also is a good target in evaluation of disease extent in patients with ESCC.