Hu Jian, Pei Wenceng, Jiang Minren, Huang Ying, Dong Fuyun, Jiang Zhenyou, Xu Ying, Li Zihuang
Department of Oncology Radiotherapy, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China.
Department of Gastroenterology, Civil Aviation Hospital of Shanghai, Shanghai, China.
Cancer Cell Int. 2022 Mar 5;22(1):107. doi: 10.1186/s12935-022-02487-0.
DFNA5 (GSDME) belongs to Gasdermin familily that is involved in a variety of cancers and triggers cell pyroptosis after chemical treatment. However, the relationship in DFNA5 between prognosis and immune cells in diverse cancers has been receiving little attention. Tumor immune cells infiltration and exhaustion may associate with patients prognosis. The roles of DFNA5 in tumor immune cells infiltration and exhaustion have not been clarified.
The expression level of DFNA5 was determined by the Tumour Immune Estimation Resource and the Oncomine database. Then the impacts of DFNA5 in prognosis were assessed by Kaplan-Meier plotter and ULACAN. The correlations between DFNA5 and tumour-infiltrating lymphocytes were explored by TIMER. In addition, the relationships in the expression levels of DFNA5 and typical genes combination of tumour-infiltrating lymphocytes were analysed by GEPIA and TIMER. In this study, we screened the chemokine and immune related proteins interacted with DFNA5 using TurboID system to explore the instantaneous or weak interactions.
DFNA5 significantly influences the prognosis in different cancers according to The Cancer Genome Atlas (TCGA). The expression levels of DFNA5 showed positive correlations to the infiltration of macrophages, CD8 + T cells, CD4 + T cells in liver hepatocellular carcinoma (LIHC), colon adenocarcinoma (COAD), and lung adenocarcinoma (LUAD). DFNA5 expression displayed obvious correlations with multiple lymphocytes gene makers in COAD, LIHC and LUAD. DFNA5 expression has effects on the prognosis of liver hepatocellular carcinoma and LUAD. DFNA5 upregulated the expression levels of PDCD1 and CD274 in a dose-dependent manner. Chemokine and immune related proteins interact with DFNA5.
These results indicate that DFNA5 is related to patient prognosis and immune cells, consisting of macrophages, CD4 + T cells, and CD8 + T cells, in diverse cancers. In addition, DFNA5 expression might contribute to the regulation of T cell exhaustion, tumour-associated macrophages (TAMs), and Tregs in COAD, LIHC and LUAD. DFNA5 may regulate immune infiltration via EIF2AK2. IFNGR1 was related to the functions of PD-L1 expression and PD-1 checkpoint pathway. These results indicate that DFNA5 levels may be act as a prognostic factor and predict the degrees of immune cells infiltration in LIHC and LUAD.
DFNA5（GSDME）属于Gasdermin家族，参与多种癌症，并在化学处理后引发细胞焦亡。然而，DFNA5在不同癌症中的预后与免疫细胞之间的关系一直未受到太多关注。肿瘤免疫细胞浸润和耗竭可能与患者预后相关。DFNA5在肿瘤免疫细胞浸润和耗竭中的作用尚未阐明。
通过肿瘤免疫评估资源和Oncomine数据库确定DFNA5的表达水平。然后通过Kaplan-Meier绘图仪和ULACAN评估DFNA5对预后的影响。通过TIMER探索DFNA5与肿瘤浸润淋巴细胞之间的相关性。此外，通过GEPIA和TIMER分析DFNA5表达水平与肿瘤浸润淋巴细胞典型基因组合之间的关系。在本研究中，我们使用TurboID系统筛选与DFNA5相互作用的趋化因子和免疫相关蛋白，以探索瞬时或弱相互作用。
根据癌症基因组图谱（TCGA），DFNA5显著影响不同癌症的预后。在肝细胞癌（LIHC）、结肠腺癌（COAD）和肺腺癌（LUAD）中，DFNA5的表达水平与巨噬细胞、CD8 + T细胞、CD4 + T细胞的浸润呈正相关。DFNA5表达与COAD、LIHC和LUAD中的多种淋巴细胞基因标志物显示出明显的相关性。DFNA5表达对肝细胞癌和LUAD的预后有影响。DFNA5以剂量依赖的方式上调PDCD1和CD274的表达水平。趋化因子和免疫相关蛋白与DFNA5相互作用。
这些结果表明，DFNA5与不同癌症患者的预后和免疫细胞有关，这些免疫细胞包括巨噬细胞、CD4 + T细胞和CD8 + T细胞。此外，DFNA5表达可能有助于调节COAD、LIHC和LUAD中的T细胞耗竭、肿瘤相关巨噬细胞（TAM）和调节性T细胞。DFNA5可能通过EIF2AK2调节免疫浸润。IFNGR1与PD-L1表达和PD-1检查点通路的功能有关。这些结果表明，DFNA5水平可能作为预后因素，并预测LIHC和LUAD中免疫细胞浸润的程度。
Zotero 插件
