Expression and prognostic analyses of the insulin-like growth factor 2 mRNA binding protein family in human pancreatic cancer

Abstract

Background Despite advances in early diagnosis and treatment, cancer remains the leading cause of mortality worldwide. The insulin-like growth factor 2 mRNA binding protein (IGF2BP) family has been reported to be involved in a variety of human malignant tumours. However, little is known about their expression and prognostic value in human pancreatic cancer. Therefore, we performed a detailed cancer versus normal differential analysis. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to analyse the mRNA expression levels of the IGF2BP family in various cancers, including pancreatic cancer. Then, the LinkedOmics and GEPIA databases were used to assess the relation between the expression levels of IGF2BPs and overall survival (OS). Then, univariate and multivariate Cox regression analyses were performed, and subgroups based on grade and stage were analysed. The signalling pathways associated with IGF2BP2 and IGF2BP3 were then investigated via gene set enrichment analysis (GSEA). Results IGF2BP2 and IGF2BP3 were associated with each subset of OS based on grade and stage. Further clinical correlation analysis of IGF2BP2 and IGF2BP3 confirmed that IGF2BP2 and IGF2BP3 are fundamental factors in promoting pancreatic cancer progression. Conclusion IGF2BP2 and IGF2BP3 are key factors in promoting the progression of pancreatic cancer and are closely related to overall survival.

Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis

“…Lastly, in order to further verify the expression status of altered RBPs in pancreatic cancer cell lines and tissue samples, we explored the published literature and used The Protein Atlas data. There were multiple studies where actually the expression of these specific RBPs was estimated in several pancreatic cancer cell lines or patient tissues using qPCR and/or Western blotting or immunohistochemical analysis; convincingly supporting our results ( Supplementary Table S8 ) ( Fernández-Salas et al, 2000 ; Kong et al, 2010 ; Bhatti et al, 2011 ; Taniuchi et al, 2014a ; Cai et al, 2015 ; Taniuchi et al, 2015 ; Schultz et al, 2017 ; Tang et al, 2017 ; Yu et al, 2017 ; Nguyen et al, 2019 ; Cui et al, 2020 ; Konishi et al, 2021 ). Immunohistochemistry results for IGF2BP3, PAIP2B, and SIDT2 have already been shown in Figure 2 , and we additionally present the results for the rest of the five RBPs in pancreatic cancer tissues as shown in Supplementary Figure S4 , which strongly validate their expression in patient samples signifying their importance in the disease.…”

Whole genome sequencing identifies rare germline variants enriched in cancer related genes in first degree relatives of familial pancreatic cancer patients

“… 41 The presently detected missense mutations in the gene may cause dysregulation of its tumor suppressor activity, thereby promoting the development of PDAC. Likewise, increased expression of IGF2BP3 (insulin‐like growth factor 2 mRNA‐binding protein 3) was found to promote invasiveness and metastasis of PDAC, 42 , 43 while dysregulation of SGK2 (serum/glucocorticoid regulated kinase 2) affected treatment response in PDAC. 44 The RIF1 gene has emerged as a conserved regulator of chromosome maintenance, acting to control DNA replication and repair.…”

The Emerging Role of RNA N6-Methyladenosine Modification in Pancreatic Cancer

“…Consistent with IGF2BP1, IGF2BP2 was also significantly upregulated in PC tissues and cell lines (128,(169)(170)(171)(172) (Table 4). A high expression of IGF2BP2 predicted a shorter OS of PC patients (128,(160)(161)(162)(169)(170)(171)(172)(173) (Table 4). Knockdown of IGF2BP2 significantly reduced PC cell growth and invasion (128,162,169,171,172) (Table 4).…”