Systematic Analysis of the Expression Profile and Prognostic Significance of the IGF2BP Family in Lung Adenocarcinoma

Abstract

Background: Lung adenocarcinoma (LUAD)，the most common type of lung cancer associated with poor prognosis, has become a major health problem for human health. IGF2BPs are types of N6-methyladenosine reader proteins, comprising IGF2BP1, IGF2BP2, and IGF2BP3, that promote LUAD progression. However, the expression profiles and prognostic value of IGF2BPs in LUAD remain unclear. Objective: To analyze the expression profiles and prognostic significance of the IGF2BP family in lung adenocarcinoma. Methods: In our study, we utilized LUAD patient and normal or para-carcinoma tissue data from TCGA database and the GTEx project. Using survival analysis, Kaplan–Meier curves, and Cox proportional hazards model, we analyzed the expression profiles and prognostic significance of the IGF2BP family. Results: Patients with high expression levels of IGF2BPs showed significant association with poor overall survival (p < 0.05). Moreover, the somatic mutation rates of IGF2BP1, IGF2BP2, IGF2BP3 were determined as 2.65, 1.59, and 1.76%, respectively, by investigating the genetic mutation. In addition, there were significant associations between TMB and IGF2BP family expression profiles, which positively correlated with the expression of PD-1 (p < 0.05). Cox proportional hazard model for LUAD showed the risk score for IGF2BP1, p-TNM stage, and so forth, all independent prognostic indicators for LUAD patients. Finally, the co-expression genes were obtained to build a PPI network and analyze the hub genes of the IGF2BP family. Conclusion: Our study provides further insights into the role of the IGF2BP family in LUAD and identifies 10 genes that may be associated with IGF2BPs in LUAD patients.

IGF2BP2, an RNA‐binding protein regulates cell proliferation and osteogenic differentiation by stabilizing SRF mRNA

“…IGF2BP regulatory proteins are RBPs that modulate cellular functions including cell proliferation, differentiation, migration, and cancer invasion (Ramesh‐Kumar & Guil, 2022). We have previously shown that IGF2BP2 protein expression plays a significant role in lung adenocarcinoma development and progression (Zhou et al, 2022). IGF2BP family proteins are N 6 ‐methyladenosine (m 6 A) regulators.…”

m6A readers, writers, erasers, and the m6A epitranscriptome in breast cancer

“…YTHDF1, with METTL14, promoted double-stranded break (DSB) DNA damage repair and YTHDF1 knockdown increased sensitivity to adriamycin, cisplatin, and olaparib in MDA-MB-231 cells (Sun et al 2022). FOXM1, which promotes BC metastasis, is a YTHDF1 target and binding of YTHDF1 to FOXM1 mRNA for accelerated translation of FOXM1 in MCF-7 cells (Chen et al 2022). Binding of YTHDF1 to PKM2 mRNA stabilized the transcript to increase translation efficiency, which increased glycolytic activity in MBA-MD-231 and MCF-7 cells (Yao et al 2022).…”

“…For example, HNRNPC expression promoted cell proliferation by inducing MAPK signaling in MDA-MB-231 and MCF-7 cells (Lv et al 2021). HNRNPK promotes invasion and metastasis in MDA-MB-231 and MDA-MB-468 cells by interacting with PROX1 and stimulating the WNT pathway (Zhu et al 2022).…”

Roles and therapeutic implications of m6A modification in cancer immunotherapy

“…Simultaneously, FTO inhibition enhances the response to anti-PD-1 therapy in mice ( 130 ). The IGF2BP family, a regulatory subunit of m6A readers, is positively correlated with PD-1 expression, demonstrating that m6A modification regulated by the IGF2BP family may have potential benefits for patients with lung adenocarcinoma treated with ICIs ( 133 ). In recent years, integrative and comprehensive genomic and molecular analyses have been established to explore potential prognostic targets predicting the response of patients with pancreatic cancer to immunotherapy.…”