Abstract
Tumor mutation burden (TMB) was a promising marker for immunotherapy. We aimed to investigate the prognostic role of TMB and its relationship with immune cells infiltration in gastric cancer (GC). We analyzed the mutation landscape of all GC cases and TMB of each GC patient was calculated and patients were divided into TMB-high and TMB-low group. Differentially expressed genes (DEGs) between the two groups were identified and pathway analysis was performed. The immune cells infiltration in each GC patient was evaluated and Kaplan–Meier analysis was performed to investigate the prognostic role of immune cells infiltration. At last, hub immune genes were identified and a TMB prognostic risk score (TMBPRS) was constructed to predict the survival outcome of GC patients. The relationships between mutants of hub immune genes and immune infiltration level in GC was investigated. We found higher TMB was correlated with better survival outcome and female patients, patients with T1-2 and N0 had higher TMB score. Altogether 816 DEGs were harvested and pathway analysis demonstrated that patients in TMB-high group were associated with neuroactive ligand–receptor interaction, cAMP signaling pathway, calcium signaling pathway. The infiltration of activated CD4+ memory T cells, follicular helper T cells, resting NK cells, M0 and M1 macrophages and neutrophils in TMB-high group were higher compared than that in TMB-low group and high macrophage infiltration was correlated with inferior survival outcome of GC patients. Lastly, the TMBPRS was constructed and GC patients with high TMBPRS had poor prognosis.
Highlights
According to the statistics in 2018, over 1 million newly diagnosed cases and almost 800000 cancer-related deaths have made gastric cancer (GC) one of the most intractable diseases worldwide
We obtained the somatic mutation data of GC patients from The Cancer Genome Atlas (TCGA) and chose the data processed by VarScan software
Human programmed death-1 (PD-1) is expressed on the surface of T cells and binds to the programmed death ligand 1 (PD-L1)/PD-L2 that are present on antigen-presenting cells (APCs)
Summary
According to the statistics in 2018, over 1 million newly diagnosed cases and almost 800000 cancer-related deaths have made gastric cancer (GC) one of the most intractable diseases worldwide. GC is ranked third in terms of incidence and fifth in terms of mortality [1]. The only curative measure for GC patients is surgery [2]. Most of the cases are diagnosed in advanced stage making complete resection impossible [3]. The prognosis of GC patients is partially decided by whether lymph nodes were involved [4]. Chemotherapy before or after surgery was proved to increase the benefit of patients. Monoclonal drugs target human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor receptor 2 (VEGFR2) have been applied in the clinical practice [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
