The Therapeutic And Prognostic Value Of Immune Factors In Gastric And Colon Cancer

Objective: Gastric cancer and colon cancer are the most common malignant cancer in human digestive system.According to the Global Cancer(GLOBOCAN)2018,in2018,the number of new cases of gastric cancer and colon cancer in the world were1.03 million and 1.09 million,respectively.With the improvement of diagnosis and treatments,the overall survival of patients with gastric cancer and colon cancer has been extended.However,due to the insidious onset and rapid progress,most patients have extensive infiltration and metastasis when diagnosed.In addition,there is still a lack of effective treatment for advanced gastric cancer and colon cancer,with great differences in clinical treatment benefits between individuals and poor prognosis.Therefore,there is an urgent need to explore new therapeutic targets and prognostic biomarkers.The occurrence and development of malignant tumors are closely related to the immune system of the body.In recent years,anti-tumor immunotherapy has developed rapidly,such as oncolytic viruses therapy,Chimeric antigen receptor redirected T cells(CAR-Ts)and immune checkpoint inhibitors,etc.The immune status of patients and tumor infiltrating immune cells are important influencing factors of anti-tumor immunity and have prognostic significance.Therefore,the therapeutic and prognostic value of immune factors in gastric cancer and colon cancer has important research significance.Methods:Part 1: Explore the ceRNA regulatory network of the B7 family in gastric cancer(1)The expression characters of each member of the B7 family in gastric cancer and adjacent tissues are analyzed in the TCGA datasets and GEPIA online database;(2)Bioinformatics analysis are used to screen the upstream regulatory micro RNA and lncRNA of the B7 family in gastric cancer,and construct a ceRNA regulatory network;(3)qRT-PCR are used to verify the predicted ceRNA regulatory network;Part 2: Explore the prognostic value of peripheral blood immune cell subsets in metastatic colon cancer.(1)This study collected 158 patients with metastatic colon cancer.Patients’ medical records and genetic test reports were inquired.(2)Chi-square test was used to analyze the relationship between baseline peripheral blood immune cell subsets and clinicopathological parameters;(3)Kaplan-Meier and Log-rank tests were used to analyze the relationship between clinicopathological parameters and baseline peripheral immune cell subsets and OS of patients with metastatic colon cancer.(4)COX univariate/multivariate regression analysis was used to identify the indendent factors in metastatic colon cancer;Results: Part 1: 1.The expression levels of B7-H3 and B7-H5 are the highest in gastric cancer tissues;compared with normal tissues,B7-2,B7-H2,B7-H3,B7-H6,and B7-H7 are up-regulated in gastric cancer tissues;2.lncRNA XIST and COX10-AS1 may act as ceRNA on B7 family by regulating miR-302 family and miR-520 family;3.In HGC-27 and SNU216 gastric cancer cell lines,the expression of miR-302 family and miR-520 d was up-regulated,and the expression of other B7 family members except B7-1 was down-regulated after knocking down COX10-AS1 and XIST.Part2:Chi-square test results showed that the baseline peripheral blood CD4+T cells,CD3+T cells,NK cells and B cells of BRAF wild-type metastatic colon cancer patients are higher than those of BRAF mutant patients;The baseline peripheral blood CD8+T cells of KRAS wild-type patients patients are higher than those of KRAS mutant patients;2.Survival analysis showed that peripheral blood CA19-9,KRAS,BRAF are poor prognostic factors,and peripheral blood ALB,CD4+ T cells,CD8+ T cells and NK cells are protective prognostic factors for metastatic colon cancer.Especially in patients with liver metastases,normal CD4+ T cell and NK cell levels indicate a longer OS.3.Baseline peripheral blood ALB,NK cell and KRAS gene mutations are independent prognostic factors for metastatic colon cancer.Conclusion: 1.lncRNA XIST and COX10-AS1 may act as ceRNA on the B7 family by regulating the miR-302 family and the miR-520 family.2.CD4+T cells,CD8+T cells and NK cells are the protective prognostic factors of metastatic colon cancer,and NK cells are independent prognostic factors.