多组学分析 N6-甲基腺苷读码器 IGF2BP3 作为泛癌的有前途的生物标志物。
Multi-omics analysis of N6-methyladenosine reader IGF2BP3 as a promising biomarker in pan-cancer.
机构信息
Department of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
出版信息
Front Immunol. 2023 Jan 25;14:1071675. doi: 10.3389/fimmu.2023.1071675. eCollection 2023.
BACKGROUND
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) has been reported to exhibit an oncogenic effect as an RNA-binding protein (RBP) by promoting tumor cell proliferation, migration and invasion in several tumor types. However, a pan-cancer analysis of IGF2BP3 is not currently available, and the exact roles of IGF2BP3 in prognosis and immunology in cancer patients remain enigmatic. The main aim of this study was to provide visualization of the systemic prognostic landscape of IGF2BP3 in pan-cancer and to uncover the potential relationship between IGF2BP3 expression in the tumor microenvironment and immune infiltration profile.
METHODS
Raw data on IGF2BP3 expression were obtained from GTEx, CCLE, TCGA, and HPA data portals. We have investigated the expression patterns, diagnostic and prognostic significance, mutation landscapes, functional analysis, and functional states of IGF2BP3 utilizing multiple databases, including HPA, TISIDB, cBioPortal, GeneMANIA, GESA, and CancerSEA. Moreover, the relationship of IGF2BP3 expression with immune infiltrates, TMB, MSI and immune-related genes was evaluated in pan-cancer. IGF2BP3 with drug sensitivity analysis was performed from the CellMiner database. Furthermore, the expression of IGF2BP3 in different grades of glioma was detected by immunohistochemical staining and western blot.
RESULTS
We found that IGF2BP3 was ubiquitously highly expressed in pan-cancer and significantly correlated with diagnosis, prognosis, TMB, MSI, and drug sensitivity in various types of cancer. Besides, IGF2BP3 was involved in many cancer pathways and varied in different immune and molecular subtypes of cancers. Additionally, IGF2BP3 is critically associated with genetic markers of immunomodulators in various cancers. Finally, we validated that IGF2BP3 protein expression was significantly higher in glioma than in normal tissue, especially in GBM.
CONCLUSIONS
IGF2BP3 may be a potential molecular biomarker for diagnosis and prognosis in pan-cancer, especially for glioma. It could become a novel therapeutic target for various cancers.
背景
胰岛素样生长因子 2 mRNA 结合蛋白 3（IGF2BP3）已被报道作为一种 RNA 结合蛋白（RBP）发挥致癌作用，促进多种肿瘤类型的肿瘤细胞增殖、迁移和侵袭。然而，目前还没有关于 IGF2BP3 的泛癌分析，IGF2BP3 在癌症患者中的预后和免疫学中的确切作用仍然是个谜。本研究的主要目的是提供 IGF2BP3 在泛癌中的系统预后景观的可视化，并揭示肿瘤微环境中 IGF2BP3 表达与免疫浸润谱之间的潜在关系。
方法
从 GTEx、CCLE、TCGA 和 HPA 数据门户获得 IGF2BP3 表达的原始数据。我们利用多个数据库（包括 HPA、TISIDB、cBioPortal、GeneMANIA、GESA 和 CancerSEA）研究了 IGF2BP3 的表达模式、诊断和预后意义、突变景观、功能分析和功能状态。此外，在泛癌中评估了 IGF2BP3 表达与免疫浸润、TMB、MSI 和免疫相关基因的关系。从 CellMiner 数据库进行 IGF2BP3 药物敏感性分析。此外，通过免疫组织化学染色和 Western blot 检测不同级别胶质瘤中 IGF2BP3 的表达。
结果
我们发现 IGF2BP3 在泛癌中普遍高度表达，与各种类型癌症的诊断、预后、TMB、MSI 和药物敏感性显著相关。此外，IGF2BP3 参与了许多癌症途径，在不同的免疫和分子亚型癌症中存在差异。此外，IGF2BP3 与各种癌症中免疫调节剂的遗传标志物密切相关。最后，我们验证了 IGF2BP3 蛋白表达在胶质瘤中明显高于正常组织，尤其是在 GBM 中。
结论
IGF2BP3 可能是泛癌中诊断和预后的潜在分子标志物，特别是对胶质瘤。它可能成为各种癌症的新的治疗靶点。
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