焦亡核心分子GSDME作为与预后和免疫相关的肝癌新型生物标志物

Pyroptotic Core Molecule GSDME as a Novel Biomarker for Liver Cancer Related to Prog-nosis and Immunity

摘要: 目的：GSDME (DFNA5)是焦亡执行蛋白gasdermin家族基因成员之一。大量研究表明GSDME表达与肿瘤发生发展之间存在很强的相关性。然而，GSDME在肝癌中的表达和生物学功能仍不清楚。方法：我们使用TIMER2.0数据库探讨了泛癌中GSDME的mRNA表达情况。还使用GEPIA和UALCAN数据库来确定HCC中GSDME的mRNA表达和蛋白表达。UALCAN用于分析GSDME和肝癌亚组分级之间的关系。还使用Kaplan-Meier研究了GSDME的表达与肝癌预后的相关性。使用TIMER2.0数据库分析了GSDME表达与肝癌微环境中免疫细胞浸润和免疫检查点之间的相关性。免疫组织化学技术(HPA)用于探索GSDME蛋白在HCC和正常肝组织中的表达情况。结果：与正常组织相比，GSDME在肝癌中表达上调。肝癌中高GSDME表达预示有较高的组织分级、肿瘤分期和较多的淋巴结转移，同时高GSDME表达预示总生存期和疾病特异性生存期较差。GSDME的表达与肝癌中B细胞、CD4+T细胞、巨噬细胞、中性粒细胞和NK细胞的浸润水平显着相关。同时GSDME的表达与免疫治疗检查点PD-1、CTLA4和PD-L1的表达显著相关。结论：我们的研究结果表明GSDME在HCC中过表达，并且GSDME表达与HCC中的免疫浸润和预后显着相关。因此，GSDME可作为肝癌免疫治疗和预后的生物标志物。

Abstract: Objective: GSDME (DFNA5) is one of the gene members of pyroptotic executive protein gasdermin family. A large number of studies have shown that there is a strong correlation between the expres-sion of GSDME and the development of tumors. However, the expression and biological functions of GSDME in HCC remain unclear. Methods: We used the TIMER2.0 database to explore the mRNA ex-pression of GSDME in pan-cancer. The GEPIA and UALCAN databases were also used to determine the mRNA expression and protein expression of GSDME in HCC. UALCAN was used to analyze the re-lationship between GSDME and liver cancer subgroup grades. The correlation between the expres-sion of GSDME and the prognosis of liver cancer was also investigated using Kaplan-Meier. The cor-relation between GSDME expression and immune cell infiltration and immune checkpoints in the HCC microenvironment was analyzed using the TIMER2.0 database. Immunohistochemical tech-nique (HPA) was used to explore the expression of GSDME protein in HCC and normal liver tissues. Results: Compared with normal tissues, the expression of GSDME was up-regulated in HCC. High GSDME expression in HCC predicted higher tissue grade, tumor stage and more lymph node metas-tasis, while high GSDME expression predicted poor overall survival and disease-specific survival. The expression of GSDME was significantly correlated with the infiltration levels of B cells, CD4+T cells, macrophages, neutrophils and NK cells in HCC. At the same time, the expression of GSDME was significantly correlated with the expression of immunotherapy checkpoints PD-1, CTLA4 and PD-L1. Conclusion: Our findings suggest that GSDME is overexpressed in HCC, and GSDME expression is sig-nificantly associated with immune infiltration and prognosis in HCC. Therefore, GSDME may serve as a biomarker for immunotherapy and prognosis in HCC.