P14.06 Dysregulation of m6a Reader IGF2BP1 in Lung Adenocarcinoma Affects the Immune Microenvironment and Indicates a Poor Recovery

Abstract

IGFII mRNA-binding protein 1 (IGF2BP1, also known as IMP1), a m6a reader gene, expressed only in a few adult human tissues, but common highly expressed in a various of malignant tumors. Previous studies have shown that IGF2BP1 overexpression may influence MAPK/ERK signaling pathway by promoting kras or pkcα expression in breast cancer or melanoma. Inhibiting IGF2BP1 expression enhances the effects of braf-inhibitor and braf-MEK inhibitors. IGF2BP1 is also required for β-actin mRNA localization, which promote cell migration. These results drivers us to the study the function role of IGF2BP1 in LUAD initiation and progression. IGF2BP1 expression data and clinical information were abtained from RNA-sequencing datasets in TCGA. Bioinformatics analyses including differential expression analysis, and weighted gene coexpression network analysis were used to find the potential changes of gene expressions and its coexpression network. LUAD and paired tumor adjacent normal lung tisses were stained with IGF2BP1 IHC antibody to explore the protein level differences between normal and tumor tissues. Kaplan-Meier analysis, cox univariate and multivariate analyses were performed on the overall survival LUAD patients to illustrate the clinical role of IGF2BP1. Those genes coexpressed with IGF2BP1 were analyzed by Gene Ontology (GO). Transcriptome sequencing data of TCGA LUAD datasets analysis showed that IGF2BP1 transcripts was significantly highly expressed in LUAD tissues compared with normal lung tissues and was related to LUAD various clinical pathological stages. IGF2BP1 IHC analytical comparison demonstrated that LUAD tumor cells was highly stained comparable with normal cells. Kaplan-Meier analysis showed that patients with high IGF2BP1 RNA level in LUAD tissues had considerably shorter overall survival than patients low expression. Coexpression genes functional analysis were enriched with 37 GO terms. GO analysis revealed that the coexpression genes mainly participated in some immunological process including antigen processing and presentation via MHC class Ib, regulation of myeloid cell differentiation, antigen processing and presentation of endogenous antigen, positive regulation of T cell mediated cytotoxicity, regulation of T cell mediated cytotoxicity, regulation of adaptive immune response. These genes own function,such as mRNA 5'-UTR binding, enhancer sequence-specific DNA binding, enhancer binding, translation regulator activity, mRNA 3'-UTR binding, RNA polymerase II distal enhancer sequence-specific DNA binding. Our results showed that highly expressed IGF2BP1 in LUAD indicates shorter overall survival rate and poorer recovery. Its coexpression network influences the Immune microenvironment through DNA or RNA binding manner, which suggested that IGF2BP1 worked as a m6a reader might be developed as novel therapeutic targets for LUAD.