DataSheet_1_Multi-omics analysis of N6-methyladenosine reader IGF2BP3 as a promising biomarker in pan-cancer.zip

BackgroundInsulin-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.
MethodsRaw 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.
ResultsWe 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.
ConclusionsIGF2BP3 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（Insulin-like growth factor 2 mRNA-binding protein 3, IGF2BP3）作为一种RNA结合蛋白（RNA-binding protein, RBP），已被报道在多种肿瘤类型中通过促进肿瘤细胞增殖、迁移与侵袭发挥致癌作用。然而，目前尚无针对IGF2BP3的泛癌分析，其在癌症患者预后及免疫学层面的确切作用仍不明朗。本研究的核心目标是可视化呈现IGF2BP3在泛癌中的系统性预后全景图谱，并揭示肿瘤微环境中IGF2BP3表达与免疫浸润特征之间的潜在关联。
方法 IGF2BP3表达的原始数据取自基因型-组织表达（Genotype-Tissue Expression, GTEx）、癌症细胞系百科全书（Cancer Cell Line Encyclopedia, CCLE）、癌症基因组图谱（The Cancer Genome Atlas, TCGA）及人类蛋白质图谱（Human Protein Atlas, HPA）的数据门户。本研究依托HPA、TISIDB、cBioPortal、GeneMANIA、基因集富集分析（GESA）、CancerSEA等多个数据库，对IGF2BP3的表达模式、诊断与预后价值、突变全景、功能特征及功能状态展开了系统性探究。此外，本研究在泛癌队列中评估了IGF2BP3表达与免疫浸润、肿瘤突变负荷（Tumor Mutation Burden, TMB）、微卫星不稳定性（Microsatellite Instability, MSI）及免疫相关基因的相关性。通过CellMiner数据库完成了IGF2BP3的药物敏感性分析。进一步，本研究采用免疫组织化学染色与蛋白质印迹（Western Blot）实验，检测了IGF2BP3在不同级别胶质瘤中的表达水平。
结果 本研究发现，IGF2BP3在泛癌中普遍呈高表达状态，且与多种癌症的诊断、预后、TMB、MSI及药物敏感性显著相关。此外，IGF2BP3参与多条癌症相关通路，并在不同免疫亚型与分子亚型的肿瘤中存在表达异质性。同时，IGF2BP3与多种癌症的免疫调节因子遗传标记物密切关联。最后，本研究验证发现，胶质瘤组织中IGF2BP3的蛋白表达水平显著高于正常组织，尤以胶质母细胞瘤（Glioblastoma, GBM）最为显著。
结论 IGF2BP3有望成为泛癌诊断与预后评估的潜在分子生物标志物，尤其针对胶质瘤。其或可作为多种癌症的新型治疗靶点，具备潜在的临床转化价值。