Insulin-Like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1) Is a Prognostic Biomarker and Associated with Chemotherapy Responsiveness in Colorectal Cancer

Abstract

Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an RNA-binding protein and serves as a post-transcriptional fine-tuner regulating the expression of mRNA targets. However, the clinicopathological roles of IGF2BP1 in colorectal cancer (CRC) remains limited. Thus, we aimed to elucidate the clinical significance and biomarker potentials of IGF2BP1 in CRC. A total of 266 specimens from two sets of CRC patients were collected. IGF2BP1 expression was studied by immunohistochemical (IHC) staining. The Kaplan-Meier survival plot and a log-rank test were used for survival analysis. The Cox proportional hazards model was applied to determine the survival impact of IGF2BP1. Public datasets sets from The Cancer Genome Atlas (TCGA) and Human Cancer Metastasis Database (HCMDB), receiver operating characteristic (ROC) plotter, and two CRC cell lines, HCT-116 and DLD-1, were used for validating our findings. We showed that IGF2BP1 was overexpressed in tumor specimens compared to 13 paired normal parts by examining the immunoreactivity of IGF2BP1 (p = 0.045). The increased expression of IGF2BP1 in primary tumor parts was observed regardless of metastatic status (p < 0.001) in HCMDB analysis. IGF2BP1 expression was significantly associated with young age (59.6% vs. 46.7%, p-value = 0.043) and advanced stage (61.3% vs. 40.0%, p-value = 0.001). After controlling for confounding factors, IGF2BP1 remained an independent prognostic factor (HR = 1.705, p-value = 0.005). TCGA datasets analysis indicated that high IGF2BP1 expression showed a lower 5-year survival rate (58% vs. 65%) in CRC patients. The increased expression of IGF2BP1 in chemotherapy non-responder rectal cancer patients was observed using a ROC plotter. Overexpression of IGF2BP1 promoted the colony-forming capacity and 5-fluorouracil and etoposide resistance in CRC cells. Here, IGF2BP1 was an independent poor prognostic marker in CRC patients and contributed to aggressive phenotypes in CRC cell lines.

The Importance of SNPs at miRNA Binding Sites as Biomarkers of Gastric and Colorectal Cancers: A Systematic Review

“…The risk of colorectal cancer incidence significantly increases in carriers with the C allele in SNP rs6504593 located in IGF2BP1 (Insulin-Like Growth Factor-2 Binding Protein-1) [ 22 ]. Based on the literature, the expression level of IGF2BP1 in different types of cancer is changed [ 23 ]. Xie and colleagues indicated that miR-21 bound to SNP rs6504593 in IGF2BP1 could regulate the expression of IGF2BP1 and develop colorectal cancer risk.…”

m6A-binding protein IGF2BP1 promotes the malignant phenotypes of lung adenocarcinoma

“…IGF2BP1 is a new member of the m 6 A-binding proteins; it is widely expressed in the process of embryonic development and is gradually downregulated after birth. Previous research has found that IGF2BP1 has more than 3,000 mRNA targets ( 22 , 27 , 31 , 32 ). By regulating the stability of target mRNA, IGF2BP1 plays important roles in regulating cell migration, cell proliferation, and cell metabolism and maintaining the epithelial phenotype ( 13 , 23 , 27 ).…”

“…It has been shown that IGF2BP1 is associated with poor prognosis of 13 organs including lung, esophagus, breast, thyroid, and kidney ( 27 , 32 , 37 , 38 ). Conversely, there are also a small number of studies demonstrating the tumor-protective roles of IGF2BP1 in gallbladder carcinoma, colitis-associated carcinoma, colorectal cancer, and breast carcinoma ( 39 – 41 ).…”

The Insulin-like Growth Factor System and Colorectal Cancer

“…IGF2BP family consists of three members which exert negative effects in the late phase of embryo development; their expression is lost in adults and may be reactivated in tumors [ 181 , 182 ]. IGF2BP1 was evaluated as an independent prognostic marker in CRC associated with the responsiveness to chemotherapy [ 183 ]. Although IGF2BP expression is generally related to worse prognosis, opposing overall effects of different IGF2BP members in different cells were detected [ 48 ].…”