Xiao Chen, Dong Tao, Yang Linhui, Jin Liangzi, Lin Weiguo, Zhang Faqin, Han Yuanyuan, Huang Zhijian
Department of Gastroenterology, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, China.
Department of Digestion, Yidu Central Hospital of Weifang, Weifang, China.
Front Oncol. 2022 May 18;12:904304. doi: 10.3389/fonc.2022.904304. eCollection 2022.
Gastric cancer (GC) is the fifth commonest cancer and the third commonest reason of death causing by cancer worldwide. Currently, tumor immunology and ferropotosis develop rapidly that has made gastric cancer be treated in new directions. So, finding the potential targets and prognostic biomarkers for immunotherapy combined with ferropotosis is urgent.
By mining TCGA, immune-related genes, ferropotosis-related genes and immune-ferropotosis-related differentially expressed genes (IFR-DEGs) were identified. The independent prognostic value of IFR-DEGs was determined by differential expression analysis, prognostic analysis, and univariate and lasso regression analysis. Then, based on the prognostic risk model, the correlation between IFR-DEGs and immune scores, immune checkpoints were evaluated. Besides, we predicted the response of high and low risk groups to drugs.
A 15-gene prognostic feature was constructed. The high-risk group had a poorer prognosis than the low-risk group. High-risk group had higher level of Treg immune cell infiltration compared with that in the low-risk group, and the tumor purity, immune checkpoint PD-1 and CTLA4, and immunity in the high-risk group were higher than those in the low-risk group. These results indicate that immune ferropotosis-related genes migh be potential predictors of STAD's response to ICI immunotherapy biomarkers. In addition, the response of small molecule drugs such as Nilotini, Sunitinib, Imatinib, etc. for high and low risk groups was predicted.
IFRSig can be regarded as an independent prognostic feature and may estimate OS and clinical treatment response in patients with STAD. IFRSig also has important correlation with immune microenvironment. A new understanding of the immune-ferropotosis-related genes during the occurrence and development of STAD is provided in this study.
胃癌（GC）是全球第五大常见癌症，也是癌症导致死亡的第三大常见原因。目前，肿瘤免疫学和铁死亡发展迅速，为胃癌治疗带来了新方向。因此，迫切需要寻找免疫治疗联合铁死亡的潜在靶点和预后生物标志物。
通过挖掘TCGA数据库，鉴定免疫相关基因、铁死亡相关基因以及免疫 - 铁死亡相关差异表达基因（IFR - DEGs）。通过差异表达分析、预后分析以及单变量和套索回归分析确定IFR - DEGs的独立预后价值。然后，基于预后风险模型，评估IFR - DEGs与免疫评分、免疫检查点之间的相关性。此外，我们预测了高风险组和低风险组对药物的反应。
构建了一个包含15个基因的预后特征。高风险组的预后比低风险组差。与低风险组相比，高风险组的调节性T细胞（Treg）免疫细胞浸润水平更高，且高风险组的肿瘤纯度、免疫检查点PD - 1和CTLA4以及免疫水平均高于低风险组。这些结果表明，免疫铁死亡相关基因可能是胃腺癌（STAD）对免疫检查点抑制剂（ICI）免疫治疗生物标志物反应的潜在预测指标。此外，还预测了尼罗替尼、舒尼替尼、伊马替尼等小分子药物对高风险组和低风险组的反应。
IFRSig可被视为一个独立的预后特征，可能用于估计STAD患者的总生存期（OS）和临床治疗反应。IFRSig也与免疫微环境具有重要相关性。本研究为STAD发生发展过程中免疫 - 铁死亡相关基因提供了新的认识。
