Xie Hao, Wu Zhaoying, Li Zhenhan, Huang Yong, Zou Junwei, Zhou Hailang
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Wannan Medical College, Wuhu, China.
School of Clinical Medicine, Wannan Medical College, Wuhu, China.
Front Genet. 2022 Aug 22;13:995333. doi: 10.3389/fgene.2022.995333. eCollection 2022.
ZEB2 is a protein-coding gene that is differentially expressed in tumors and can regulate the growth of tumor cells. This study investigated the specific regulatory mechanism of ZEB2 in COAD, a common cancer with high rates of morbidity and mortality. Multi-omics panoramic display of expression and function of ZEB2 in colon cancer. R software was used to study the expression of ZEB2 in 33 types of cancer. Furthermore, RT-PCR was used to detect the expression of ZEB2 in colon cancers and para-cancer tissues, as well as in colon cancer cells and normal cells. The ssGSEA was then used to explore the relationship between ZEB2 and immune cells, with UALCAN, EWAS and MEXPRESS applied to explore the methylation of ZEB2. The relationship between immunomodulators and chemokines (or receptors) based on expression data, copy number data, methylation data, and mutation data of ZEB2 was investigated using TISIDB. Finally, a protein interaction network of ZEB2 was constructed, and GO and KEGG analyses were performed on the differentially expressed genes. ZEB2 is downregulated in most cancers, including COAD. The infiltration of the immune cells NK CD56 and Th17 cells was negatively correlated with ZEB2 expression, while the other 22 cells were positively correlated with ZEB2 expression. The DNA methylation of ZEB2 and the methylation of the ZEB2 protein on the EWAS website increased significantly. Analysis of the methylation levels and ZEB2 expression revealed that only the DNA methylation level and the expression of ZEB2 were significantly negatively correlated. The tumor-infiltrating lymphocytes positively correlated with the expression of ZEB2 but negatively correlated with the methylation of ZEB2. The same trend was observed for immunomodulators, chemokines, and receptors. The network showed that the protein performed certain biological functions, thereby affecting disease symptoms. These findings provide evidence that ZEB2-based therapy may represent a powerful treatment strategy for COAD.
ZEB2是一种在肿瘤中差异表达且可调节肿瘤细胞生长的蛋白质编码基因。本研究探讨了ZEB2在发病率和死亡率较高的常见癌症——结肠癌（COAD）中的具体调控机制。对ZEB2在结肠癌中的表达和功能进行多组学全景展示。使用R软件研究ZEB2在33种癌症中的表达。此外，采用RT-PCR检测ZEB2在结肠癌组织、癌旁组织、结肠癌细胞和正常细胞中的表达。然后使用单样本基因集富集分析（ssGSEA）来探究ZEB2与免疫细胞之间的关系，运用UALCAN、表观基因组关联研究（EWAS）和MEXPRESS来探究ZEB2的甲基化情况。利用TISIDB基于ZEB2的表达数据、拷贝数数据、甲基化数据和突变数据研究免疫调节剂与趋化因子（或受体）之间的关系。最后，构建ZEB2的蛋白质相互作用网络，并对差异表达基因进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析。ZEB2在包括COAD在内的大多数癌症中表达下调。免疫细胞自然杀伤细胞（NK）CD56和辅助性T细胞17（Th17）的浸润与ZEB2表达呈负相关，而其他22种细胞与ZEB2表达呈正相关。ZEB2的DNA甲基化以及EWAS网站上ZEB2蛋白的甲基化显著增加。甲基化水平与ZEB2表达分析表明，只有DNA甲基化水平与ZEB2表达呈显著负相关。肿瘤浸润淋巴细胞与ZEB2表达呈正相关，但与ZEB2甲基化呈负相关。免疫调节剂、趋化因子和受体也观察到相同趋势。该网络表明该蛋白质发挥了某些生物学功能，从而影响疾病症状。这些发现为基于ZEB2的治疗可能成为COAD的有效治疗策略提供了证据。
