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

Hung-Ming Chen,Shung-Haur Yang,Jeng-Kai Jiang,Ching-Liang Ho,Hao-Wei Teng,Chung-Chi Yang,Shih-Ching Chang,Wei-Lun Hwang,Yee Chao,Wei-Shone Chen,Shih-Ching Huang,Tsai-Tsen Liao,Chun-Chi Lin

doi:10.3390/ijms22136940

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.

Highlights

Colorectal cancer (CRC) is one of the most malignant cancers globally
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) Was Overexpressed in colorectal cancer (CRC) Tumors Comparing to Normal Counterparts
In an attempt to explore the clinical significance of IGF2BP1 in the tumorigenesis and progression of CRC, we collected two sets of CRC specimens and examined the expression level of IGF2BP1 at the protein level by IHC staining

Summary

Introduction

Colorectal cancer (CRC) is one of the most malignant cancers globally. It was estimated that more than 1.8 million new CRC cases and 881,000 CRC-related deaths occurred in 2018 [1,2]. Around one-third of patients with stage I–III CRC advanced to metastatic CRC (mCRC). 30–40% of patients with CRC were stage. Despite advances in chemotherapy, including 5-fluorouracil (5-FU), irinotecan, oxaliplatin, bevacizumab, cetuximab, regoragenib, lonsurf, BRAF inhibitors, and anti-PD-L1/PD-1 agents, the median overall survival (OS) in mCRC is approximately. CRC patients often suffered from drug resistance, which is positively associated with poor prognosis of CRC [4]. There is a need to find new druggable targeted genes for treating patients with metastatic CRC

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