The PD-L1 Expression And Contrast-enhanced Ultrasonography In Gastric Cancer And Their Clinical Significance

BackgroundGastric cancer is one of the most common malignant cancers in the world,with high morbidity and mortality rate.Because of the primary cancer's biological characteristics,combined with recurrence after treatment and the fact that most patients are diagnosed at a developed stage,the prognosis of gastric cancer remains poor,with 5-year survival rates low as 25%~30% in advanced patients.Currently the treatment for advanced stages the combined methods of surgery,chemotherapy and radiotherapy.Due to the absence of efficient treatment methods,and the lack of mechanisms to monitor metastasis and predicting prognosis,the standard therapies among advanced gastric cancer patients does not reach satisfactory results in patients' survival.Accumulating studies show that PD-1/PD-L1 pathway plays a major role in immunosuppression of the microenviroment of tumors,PD-L1 increases apoptosis of antigen-specific human T-cell clones and inhibits the activation of CD4 and CD8 T-cells in vitro.Clinical evidence shows that blocking PD-1/PD-L1 pathway can reinforce T cell functions.Clinical trials of monoclonal antibodies targeting PD-1/PD-L1 in gastric carcinoma displayed some positive results,but the objective remission rate maintain low,with many side effects.Despite many controversies on predictions of the prognosis of anti-PD-L1 immunotherapy,most studies show that it's a significant factor.The underlying mechanisms between the expression of PD-L1 and the clinical pathology and prognosis of gastric carcinoma remain ambiguous;furthermore,individual biomarkers cannot represent the prognosis integratively.The use of contrast-enhanced ultrasonography(CEUS)has its many benefits comparing to traditional CT scans,including detecting the depth of invasions in gastric cancers,accurately detecting metastasis in abdominal cavity lymph nodes,aiding the diagnosis of gastric cancers.This paper is based on the preliminary studies,bring together the expression of a biomarker PD-L1 and the results of transabdominal sonography and contrast-enhanced ultrasonography,assessing the correlations betweent the two,and ultimately whether it's beneficial for the prognosis of gastric cancer patients.Objectives1.Review the correlations between the expression of PD-L1 of gastric adenocarcinoma and its clinical pathology2.Assess the correspondence between the expression of PD-L1 and gastric cancer ultrasonography results.3.Assess the correspondence between the expression of PD-L1 and gastric cancer CEUS results.4.Assess the correspondence between the expression of PD-L1,gastric cancer CEUS results and the prognosis of patients.Methods1.A total number of 105 patients diagnosed with gastric carcinoma after sugery were enrolled in the study,their clinical datas were gathered and a followup up to 42 months ensued.2.PD-L1 expression of all surgical specimens were analyzed by immunohistochemical examinations.3.Record and analyze all the results of transabdominal sonography and CEUS.4.Assess the correspondence between the expression of PD-L1,gastric cancer CEUS results and the prognosis of patients.Results1.The clinical data of 105 patients diagnosed with gastric carcinoma after surgery were gathered,consisting of 71 male and 34 female,the average age is 51.11 years old.Followup from 36 months to 66 months(42 months average),median survival time is 24.0 months.2.The expression of PD-L1 is irrelevant with age,sex and the size of the tumor.However,it is highly expressed in tumors with deep invasion(P=0.040),metastasis in the lymph nodes(P=0.020)and high defferentiation.(P=0.040)3.Assessing the correspondence between the expression of PD-L1 and gastric cancer ultrasonography results show that PD-L1 is highly expressed in the following cases: hypoechoic tumors,gastric wall thickness >7mm,tumors located at the antrum,peripheral invasions.4.Assessing the correspondence between the expression of PD-L1 and gastric cancer CEUS results show that the intensity of CEUS is positively correlated with expression of PD-L1(P=0.0003).5.52 cases of high expression of PD-L1,53 cases of low expression,the MST of both groups is 20.0 months and 33.0 months,respectively,indicating significant difference.(HR 1.93;95% CI: 1.123-3.320,P= 0.017)6.56 patients has CEUS results,21 strong positive cases and 35 negative cases,the MST of both group is 16.5 months and 34.0 months,respectively,indicating significant difference.(HR 3.85;95%CI,1.535-9.679,P=0.004)7.13 cases show both PD-L1 high expression and strong postitve CEUS results(24%),the MST is 16.0 months;28 cases show both negative(50%),with its MST goes beyond the deadline,indicating significant differences.(HR:5.18;95%CI: 2.08-12.92,P=0.0004)Conclusions1.The expression of PD-L1 is irrelevant with age,sex and the size of the tumor.It is relevant with the depth of invasion,level of defferentiation and severity of metastasis.High expressions of PD-L1 are found in tumors with deep invasion,metastasis in the lymph nodes and high defferentiation.2.Assessing the correspondence between the expression of PD-L1 and gastric cancer ultrasonography results show that the expression of PD-L1 is irrelevant with metastasis of neighboring lymph nodes.It is correlated with hypoechoic tumors,the thickness of gastric wall,the position of the tumor and peripheral invasions.PD-L1 is highly expressed in the following cases: hypoechoic tumors,gastric wall thickness >7mm,tumors located at the antrum,peripheral invasions.3.The intensity of CEUS is correlated with expression of PD-L1,high intensities show high expressions of PD-L1.4.Patients with both high PD-L1 expression and strong positive CEUS results have overall shorter survival time,the difference has statistical significance.5.Ultrasonography and CEUS parameter could be considered as the predictors of the response of PD-L1 blocker treatment in clinical practice.