Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, PR China.
Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong Province, PR China.
Clin Immunol. 2022 Jul;240:109045. doi: 10.1016/j.clim.2022.109045. Epub 2022 May 23.
By multiple transcriptome datasets (TCGA, GSE59102, GSE25727, GSE27020 and GSE65858) and multi-omics (RNA-seq, SNP, CNV, DNA methylation) in-depth analysis, we found that cancer germline antigen (CGA) family/genes MAGEB2 is involved in the imitation, progression and prognosis in LC as well as correlated positively with lymphatic metastasis and negatively with DNA methylation. Then, in vitro experiment verified that MAGEB2 expression renders significant alteration in LC tissues and cells via immunohistochemical (IHC), qRT-PCR and western blot (WB), and up-regulation of MAGEB2 expression could facilitate the proliferation, migration and invasion of LC cells and vice versa. Subsequently, MAGEB2 knockdown suppressed tumor growth and lung metastasis in vivo animal experiment, while MAGEB2 overexpression promoted tumor growth and lung metastasis. Lastly, MAGEB2 is significantly associated with immune cell infiltration (CD8+ T cells particularly, IHC staining confirmed that as the protein expression of MAGEB2 increased, the protein level of CD8 (representing tumor-infiltrating CD8 + T cells) decreased in vitro), immunomodulators (knockdown or overexpression of MAGEB2 on LC cell lines can significantly affect the chemokine/cytokine secretion in vitro), and immunogenicity(TMB) in LC, which hints that MAGEB2 is tightly correlated with immune characteristics and might guide more effective immunotherapy strategies for LC patients.
通过多个转录组数据集（TCGA、GSE59102、GSE25727、GSE27020 和 GSE65858）和多组学（RNA-seq、SNP、CNV、DNA 甲基化）的深入分析，我们发现癌症种系抗原（CGA）家族/基因 MAGEB2 参与了 LC 的模拟、进展和预后，并与淋巴转移呈正相关，与 DNA 甲基化呈负相关。然后，体外实验通过免疫组织化学（IHC）、qRT-PCR 和 Western blot（WB）验证了 MAGEB2 表达在 LC 组织和细胞中发生了显著改变，上调 MAGEB2 表达可促进 LC 细胞的增殖、迁移和侵袭，反之亦然。随后，在体内动物实验中，MAGEB2 敲低抑制了肿瘤生长和肺转移，而 MAGEB2 过表达促进了肿瘤生长和肺转移。最后，MAGEB2 与免疫细胞浸润（尤其是 CD8+T 细胞）显著相关（IHC 染色证实，随着 MAGEB2 蛋白表达的增加，体外 CD8（代表肿瘤浸润性 CD8+T 细胞）的蛋白水平降低）、免疫调节剂（LC 细胞系中 MAGEB2 的敲低或过表达可显著影响体外趋化因子/细胞因子的分泌）和 LC 的免疫原性（TMB），这表明 MAGEB2 与免疫特征密切相关，可能为 LC 患者指导更有效的免疫治疗策略。
