Prognostic impact and immunotherapeutic implications of NETosis‐related gene signature in gastric cancer patients

肿瘤科 内科学 医学 癌症 比例危险模型 免疫疗法 基因 生物 遗传学
作者
Tian Xia,Zhenhua Wei,Hongzhi Wang,Gao-Min Liu
出处
期刊:Journal of Cellular and Molecular Medicine [Wiley]
标识
DOI:10.1111/jcmm.18087
摘要

Abstract The role of NETosis and its related molecules remains unclear in gastric cancer. The data used in this study was directly downloaded from the Cancer Genome Atlas (TCGA) database. All analysis and plots are completed in R software using diverse R packages. In our study, we collected the list of NETosis‐related genes from previous publications. Based on the list and expression profile of gastric cancer patients from the TCGA database, we identified the NETosis‐related genes significantly correlated with patients survival. Then, CLEC6A, BST1 and TLR7 were identified through LASSO regression and multivariate Cox regression analysis for prognosis model construction. This prognosis model showed great predictive efficiency in both training and validation cohorts. We noticed that the high‐risk patients might have a worse survival performance. Next, we explored the biological enrichment difference between high‐ and low‐risk patients and found that many carcinogenic pathways were upregulated in the high‐risk patients. Meanwhile, we investigated the genomic instability, mutation burden and immune microenvironment difference between high‐ and low‐risk patients. Moreover, we noticed that low‐risk patients were more sensitive to immunotherapy (85.95% vs. 56.22%). High‐risk patients were more sensitive to some small molecules compounds like camptothecin_1003, cisplatin_1005, cytarabine_1006, nutlin‐3a (−)_1047, gemcitabine_1190, WZ4003_1614, selumetinib_1736 and mitoxantrone_1810. In summary, our study comprehensively explored the role of NETosis‐related genes in gastric cancer, which can provide direction for relevant studies.

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