| Objective:To explore the relationship between clinicopathological features,postoperative treatment characteristics and progonisis in patients with stage I-III gastric cancer after radical gastrectomy.We analyzed the relationship between mutated gene,TMB and prognosis in patients with stage III gastric cancer after radical gastrectomy.In the meanwhile,we tested the expression level of PD-1/PD-L1 in the tissues of gastric cancer and explored the relationship between the factors expression and prognosis.Finally,We expect to search for biomarkers that can effectively predict the risk of recurrence and metastasis,and survival prognosis.Methods:The clinical and complete follow-up data of patients with stage I-III gastric cancer who underwent radical gastrectomy in our hospital from January 2009 to December 2014 were retrospectively analyzed.The relationship between clinicopathological features,postoperative treatment characteristics and prognosis was analyzed.The mutated gene,TMB and microsatellite instability in 38 patients with stage III gastric cancer after radical gastrectomy were analyzed by Next Generation Sequencing.The postoperative tumor tissues and paracancerous histopathological sections were collected and the expression of PD-1 and PD-L1 was detected by immunohistochemistry.The SPSS 25.0 software package was used to analyze the correlation between the above factors and clinicopathological features and survival.Gene analysis and mapping were used statistical software package R,GraphPad Prism and Cluster Profiler.Results:1.A total of 334 patients with stage I-III gastric cancer were enrolled.The median follow-up time was 83.4 months.At the end of follow-up(September 1st,2018),there were 191 cases was recurrence or metastasis(57.2%)and 178 cases died(53.5%),the median DFS was 34.8months,the median OS was 61.0 months,the 5-years disease free survival rate was 45.0%,and 5-year overall survival rate was 50.1%.COX regression analysis indicated that tumor size,tumor location,presence of signet ring cell,presence of cancer nodules and TNM stages were independent prognostic factors that affect the median DFS and the median OS.2.The results of Next Generation Sequencing in 38 patients with stage III gastric cancer after radical gastrectomy showed that 63 tumour-related genes mutations were found.The top five high-frequency mutated genes were TP53(26/38),ARID1A(9/38),CCNE1(9/38),KRAS(5/38),PTEN(4/38).There was no significant difference in gene mutation frequency between the long-term survival group and the short-term survival group(P>0.05).There was no significant difference in gene mutation frequency between early and late recurrence groups(P>0.05).Through the analysis of GO gene function and KEGG pathway enrichment,it was found that the mutant genes were significantly enriched in PI3K-Akt signaling pathway and MAPK signaling pathway.Log-rank test showed that the mOS in the TMB>10 Muts/Mb group was significantly longer than the TMB<10Muts/Mb group(Not Reached VS 29.42months,P=0.038).3.The positive expression rate of PD-L1 in tumor tissues was 44.0%(147/334),which was significantly higher than that in adjacent tissues(0/20).PD-L1-positive patients had a worse prognosis than the patients with negative expression(mDFS:44.47 months VS 22.31 months,P=0.039;mOS:84.14 months VS 40.12months,P=0.006).PD-L1was an independent prognostic factor that affect the median DFS and the median OS.4.The positive expression rate of PD-1 in tumor tissues was 37.7%(126/334),which was significantly higher than that in adjacent tissues(1/20).The expression level of PD-1 did not affect mDFS and mOS.The expression level of PD-1 was not correlated with mDFS and mOS.5.There was no significant correlation between the expression of PD-L1 and PD-1 in the tissues of gastric cancer.6.There was no significant correlation between the expression of PD-L1 and TMB.Conclusion:1.The high frequency mutated genes in patients with stage Ⅲ gastric cancer were TP53,ARID1A,CCNE1,KRAS,PTEN.There was no significant difference in gene mutation frequency between the long-term survival group and the short-term survival group,and also between early and late recurrence groups.The mutant genes were significantly enriched in PI3K-Akt signaling pathway and MAPK signaling pathway.The mOS in the TMB>10 Muts/Mb group was significantly prolonged.2.Tumor size,tumor location,presence of signet ring cell,presence of cancer nodules,TNM stages and the expression of PD-L1 were independent prognostic factors that affect the median DFS and the median OS in gastric cancer patients underwent radical gastrectomy. |
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