GasderminE基因(GSDME)在耳聋和癌症中起作用。然而,在癌症中的作用和机制是复杂的,相同的基因在不同类型的癌症中表现出不同的机制和作用。在线数据库,如GEPIA2,cBioPortal,和DNMIVD,用于全面分析GSDME概况,DNA甲基化,突变,诊断,肿瘤组织和匹配的健康组织患者的预后。Western印迹和RT-PCR用于监测癌细胞系中虫草素(CD)对GSDME的调节。我们发现GSDME表达在八种癌症中显著上调(ACC,DLBC,GBM,HNSC,LGG,PAAD,SKCM,和THYM),并在七种癌症中显著下调(COAD,KICH,LAML,OV,READ,UCES,和UCS)。总生存期仅在ACC中更长,但在四种癌症中更短,包括COAD,KIRC,LIHC,STAD,与相应的正常组织相比,GSDME在癌症中高表达。此外,GSDME的高表达与ACC的不良预后呈负相关,GSDME的低表达与COAD的不良预后呈负相关,提示GSDME可能是这两种癌症类型的良好预后因素。因此,结果表明,这7个CpG位点的DNA甲基化构成了区分不同肿瘤与邻近健康组织的潜在有效标志。GSDME的基因突变在多种肿瘤中经常观察到,UCES的频率最高。此外,CD处理抑制不同癌细胞系的GSDME表达,而GSDME的过表达促进细胞迁移和侵袭。因此,我们已经系统地成功地阐明了GSDME表达谱,诊断值,和泛癌症的预后价值。用CD靶向GSDME意味着通过增加化学疗法的敏感性在某些类型的癌症中具有治疗意义和抗肿瘤作用的机制。总之,我们的研究可能为临床诊断提供策略和生物标志物,预测,和通过靶向GSDME治疗癌症。
The Gasdermin E gene (GSDME) plays roles in deafness and cancers. However, the roles and mechanisms in cancers are complex, and the same gene exhibits different mechanisms and actions in different types of cancers. Online databases, such as GEPIA2, cBioPortal, and DNMIVD, were used to comprehensively analyze GSDME profiles, DNA methylations, mutations, diagnosis, and prognosis in patients with tumor tissues and matched healthy tissues. Western blotting and RT-PCR were used to monitor the regulation of GSDME by Cordycepin (CD) in cancer cell lines. We revealed that GSDME expression is significantly upregulated in eight cancers (ACC, DLBC, GBM, HNSC, LGG, PAAD, SKCM, and THYM) and significantly downregulated in seven cancers (COAD, KICH, LAML, OV, READ, UCES, and UCS). The overall survival was longer only in ACC, but shorter in four cancers, including COAD, KIRC, LIHC, and STAD, when GSDME was highly expressed in cancers compared with the corresponding normal tissues. Moreover, the high expression of GSDME was negatively correlated with the poor prognosis of ACC, while the low expression of GSDME was negatively correlated with the poor prognosis of COAD, suggesting that GSDME might serve as a good prognostic factor in these two cancer types. Accordingly, results indicated that the DNA methylations of those 7 CpG sites constitute a potentially effective signature to distinguish different tumors from adjacent healthy tissues. Gene mutations for GSDME were frequently observed in a variety of tumors, with UCES having the highest frequency. Moreover, CD treatment inhibited GSDME expression in different cancer cell lines, while overexpression of GSDME promoted cell migration and invasion. Thus, we have systematically and successfully clarified the GSDME expression profiles, diagnostic values, and prognostic values in pan-cancers. Targeting GSDME with CD implies therapeutic significance and a mechanism for antitumor roles in some types of cancers via increasing the sensitivity of chemotherapy. Altogether, our study may provide a strategy and biomarker for clinical diagnosis,
prognostics, and treatment of cancers by targeting GSDME.