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Immune cell and immune related molecular for GC risk: A study combining the transcriptome and Mendelian randomization
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  • Shuran Chen,
  • jiabao yin,
  • pengcheng li,
  • zhong tong
Shuran Chen
Hefei City First People's Hospital
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jiabao yin
Second People's Hospital of Hefei
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pengcheng li
Hefei City First People's Hospital
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zhong tong
Hefei City First People's Hospital

Corresponding Author:[email protected]

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Abstract

Background: Gastric cancer(GC) is a common and poor prognosis malignant solid tumour, the application of immunotherapy has improved the prognosis of patients greatly, but the precise immunotherapy strategy is still the difficult problem of immunotherapy. Mendel randomization is a way to demonstrate exposure and outcomes at a causal level. Mendel randomization trial is therefore an excellent way of looking at the causal link between immune cells and the risk of GC, with the aim of providing new insights into immunotherapy regimens for GC patients. Method: Genetic instrumental variables(IVs) for GC were obtained from a genome wide association study (GWAS). Inverse-variance weighted (IVW) method was used as the primary analysis. Simple-median method, weighted-median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test were used as the further analysis. Uni-cox and lasso were used to select genes related to GC and survival model was constructed. Through many data of GC patients, we further explored the relationship between risk models and prognosis of GC patients, association between tumour mutation load(TMB) and microsatellite instability state(MSI). Result: We obtained 731 immune cells from previous studies. From these cells, we screened six immune cells closely associated with GC. Based on the SNPs of 6 immune cells, we obtained 77 genes. After Cox and lasso analysis, we obtained 5 immune cell related genes. The 5-gene risk model can divide patients into two GC groups with different prognosis. High risk GC patients had higher suppressive immune cell infiltration, lower TMB, lower tumour cell stemness, and higher TIDE scores. Conclusion: This study based on a variety of data from MR analysis demonstrated the association between immune cells and GC risk at the causal level. 6 immune cell-related genes are associated with TMB, MSI and immunotherapy sensitivity in GC patients.