Prognostic Value Of LAG-3 And Stromal Tumor-infiltrating Lymphocytes In Advanced Gastric Adenocarcinoma

Objective:This study analyzed the densities of stromal tumor-infiltrating lymphocytes and expression of LAG-3 protein in advanced gastric adenocarcinoma,to investigate the correlation between stromal tumor-infiltrating lymphocytes,LAG-3and prognosis of patients with advanced gastric adenocarcinoma.Materials and Methods:The clinicopathological characteristics and follow-up data of 260 patients with advanced gastric adenocarcinoma were collected.The percentage of stromal TILs was reported semi-quantitatively by histological section evaluation,the LAG-3 protein was detected by using Immunohistochemistry.According to the expression of Epstein-Barr virus,mismatch repair proteins,E-cadherin,and p53,260 cases of advanced gastric adenocarcinoma were divided into five subtypes.To investigate the correlation between the densities of sTIL,the expression of LAG-3protein and prognosis of patients with advanced gastric adenocarcinoma.Result:1.Clinicopathological characteristics: 260 cases of advanced gastric adenocarcinoma,with a median age 60 years(range from 17 to 87 years).There were 176 males and 84 females.The tumor size range from 1 to 17cm;88 cases occurred in the esophagus-gastric junction,85 cases occurred in the gastric fundus,80 cases occurred in the gastric antrum,7 cases occurred in the whole stomach;156 cases underwent postoperative adjuvant treatment.Histopathologically,69 were intestinal subtype,136 were diffuse subtype,and 55 were mixed type according to Lauren classification.Lymph node metastasis,ascular invasion,perineural invasion,distant metastasis were occured in 214,187,114,30,5respectively.This group of gastric cancer cases were divided into the following five subtypes: EBV-positive in 20 cases(7.7%),mismatch repair-deficient expression in 8 cases(3.1%),aberrant E-cadherin expression in 43 cases(16.5%),aberrant p53 expression in 72 cases(27.7%),normal p53 expression in 117 cases(45%).2.The densities of sTIL and expression of LAG-3 in patients with advanced gastric adenocarcinoma: Among the 260 cases,high densities of sTIL were detected in 173 cases(66.5%).LAG-3 high was observed in 160 cases(61.5%).Meanwhile,these cases were divided into four groups according to the densities of sTIL and the expression of LAG-3: typeⅠ: 48 cases(18.5%)were LAG-3 low /sTIL low;typeⅡ: 52 cases(20%)were LAG-3 low /sTIL high;typeⅢ: 39 patients(15%)were LAG-3 high /sTIL low;type Ⅳ: 121 cases(46.5%)were LAG-3 high/sTIL high.3.Prognosis: Kaplan-Meier survival analysis showed that the prognosis of patients is related to age,tumor size,tumor location,Lauren classification,perineural invasion,ascular invasion,T staging,lymph node metastasis,distant metastasis,TNM staging,postoperative adjuvant chemotherapy,protein classification(P<0.05).Meanwhile,we observed that high densities of sTIL and LAG-3 high have superior survival outcomes.COX multivariate analysis showed age(P=0.002),tumor size(P < 0.001),Lauren classification(P=0.006),postoperative adjuvant chemotherapy(P=0.028),protein classification(P=0.036)are an independent prognostic factors for patients,LAG-3 high/sTIL low is an poor prognostic factor for gastric patients.Conclusion:1.LAG-3 high and high densities of sTIL have superior survival outcomes in advanced gastric adenocarcinoma.2.Age,tumor size,Lauren classification,postoperative adjuvant chemotherapy and protein subtype were independent prognostic factors for patients with advanced gastric adenocarcinoma.3.Patients with LAG-3 high/sTIL low have poor prognosis in advanced gastric adenocarcinoma.4.LAG-3 and sTIL may be helpful in screening patients with advanced gastric adenocarcinoma with poor prognosis.