Liu Xuehe, Xie Feiyan, Ding Jin, Li Suhua, Li Jixi
State Key Laboratory of Genetic Engineering, School of Life Sciences and Huashan Hospital, Shanghai Engineering Research Center of Industrial Microorganisms, MOE Engineering Research Center of Gene Technology, Fudan University, Shanghai, China.
Clinical Cancer Institute, Center for Translational Medicine, Naval Medical University, Shanghai, China.
Front Oncol. 2023 Mar 30;13:1164214. doi: 10.3389/fonc.2023.1164214. eCollection 2023.
Gasdermin (GSDM)-mediated cell lytic death plays an essential role in immunity and tumorigenesis. Despite the association of gasdermin B (GSDMB) with the tumorigenesis of various cancers, whether GSDMB functions as a prognostic biomarker in renal cell carcinoma remains poorly understood. Here, we explored the potential immunological functions and the prognostic value of GSDMB across multiple tumors with The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, including analyzing the relationship between GSDMB expression and prognosis, tumor-immune system interactions, immunomodulators, and immune cell infiltration of different tumors. Importantly, elevated expression of GSDMB is an essential factor for the poor prognosis of kidney renal clear cell carcinoma (KIRC) patients, suggesting that it might be helpful to predict a survival benefit from a clinical therapy regimen. Furthermore, GSDMB expression promoted the level of CD4+ T-cell infiltration of the tumors but is significantly negatively associated with immature dendritic cells (iDCs) in KIRC. Additionally, we identified TNFRSF25 and TNFSF14 as immunostimulators highly correlated with GSDMB expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses showed that GSDMB and its interacting proteins might affect tumor growth through the serine metabolism pathway. Our current results demonstrate a promising therapeutic strategy targeting GSDMB and provide new insights into GSDMB as an immunological and prognostic biomarker for KIRC.
Gasdermin(GSDM)介导的细胞溶解性死亡在免疫和肿瘤发生中起着至关重要的作用。尽管gasdermin B(GSDMB)与多种癌症的肿瘤发生有关,但GSDMB在肾细胞癌中是否作为一种预后生物标志物仍知之甚少。在这里,我们利用癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据库,探索了GSDMB在多种肿瘤中的潜在免疫功能和预后价值,包括分析GSDMB表达与预后、肿瘤-免疫系统相互作用、免疫调节剂以及不同肿瘤免疫细胞浸润之间的关系。重要的是,GSDMB表达升高是肾透明细胞癌(KIRC)患者预后不良的一个重要因素,这表明它可能有助于预测临床治疗方案中的生存获益。此外,GSDMB表达促进了肿瘤中CD4 + T细胞浸润水平,但与KIRC中的未成熟树突状细胞(iDCs)显著负相关。此外,我们确定TNFRSF25和TNFSF14为与GSDMB表达高度相关的免疫刺激因子。京都基因与基因组百科全书(KEGG)和基因本体论(GO)富集分析表明,GSDMB及其相互作用蛋白可能通过丝氨酸代谢途径影响肿瘤生长。我们目前的结果证明了一种针对GSDMB的有前景的治疗策略,并为GSDMB作为KIRC的免疫和预后生物标志物提供了新的见解。