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Systematic analysis of IGF2BP family members in non-small-cell lung cancer
Liping Gong1, Qin Liu2, Ming Jia2
1Department of Academic Research, The Secondary Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China.
Background:
The insulin-like growth factor-2 mRNA-binding proteins 1, 2, and 3 (IGF2BP1, IGF2BP2, and IGF2BP3) are known to be involved in tumorigenesis, metastasis, prognosis, and cancer immunity in various human cancers, including non-small cell lung cancer (NSCLC). However, the literature on NSCLC largely omits the specific context of lung squamous cell carcinoma (LUSC), an oversight we aim to address.
Methods:
Our study evaluated the differential expression of IGF2BP family members in tumors and normal tissues. Meta-analyses were conducted to assess the prognostic value of IGF2BPs in lung adenocarcinoma (LUAD) and LUSC. Additionally, correlations between IGF2BPs and tumor immune cell infiltration, mutation characteristics, chemotherapy sensitivity, and tumor mutation burden (TMB) were investigated. GSEA was utilized to delineate biological processes and pathways associated with IGF2BPs.
Results:
IGF2BP2 and IGF2BP3 expression were found to be upregulated in LUSC patients. IGF2BP2 mRNA levels were correlated with cancer immunity in both LUSC and LUAD patients. A higher frequency of gene mutations was observed in different IGF2BP1/2/3 expression groups in LUAD compared to LUSC. Meta-analyses revealed a significant negative correlation between overall survival (OS) and IGF2BP2/3 expression in LUAD patients but not in LUSC patients. GSEA indicated a positive association between VEGF and IGF2BP family genes in LUAD, while matrix metallopeptidase activity was inversely correlated with IGF2BP family genes in LUSC. Several chemotherapy drugs showed significantly lower IC50 values in high IGF2BP expression groups in both LUAD and LUSC.
Conclusion:
Our findings indicated that IGF2BPs play different roles in LUAD and LUSC. This divergence highlights the need for tailored therapeutic strategies and prognostic tools, cognizant of the unique molecular profiles of LUAD and LUSC.
Insights
Insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) show distinct roles in lung cancer subtypes. IGF2BP2 and IGF2BP3 are upregulated in lung squamous cell carcinoma (LUSC), with varying prognostic impacts and therapeutic implications for LUSC versus lung adenocarcinoma (LUAD).
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genomics
Background:
- Insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) are implicated in various cancers, but their specific roles in lung squamous cell carcinoma (LUSC) remain under-explored.
- Existing literature on non-small cell lung cancer (NSCLC) often overlooks the distinct molecular characteristics of LUSC compared to lung adenocarcinoma (LUAD).
Purpose of the Study:
- To investigate the differential expression and prognostic significance of IGF2BP family members (IGF2BP1, IGF2BP2, IGF2BP3) in LUSC and LUAD.
- To explore the correlations between IGF2BP expression and tumor immunity, mutation profiles, chemotherapy sensitivity, and biological pathways in these lung cancer subtypes.
Main Methods:
- Differential gene expression analysis in tumor versus normal tissues.
- Meta-analyses to assess the prognostic value of IGF2BPs in LUAD and LUSC.
- Correlation analyses with tumor immune cell infiltration, mutation characteristics, TMB, and chemotherapy sensitivity.
- Gene Set Enrichment Analysis (GSEA) to identify associated biological processes.
Main Results:
- IGF2BP2 and IGF2BP3 were upregulated in LUSC. IGF2BP2 mRNA correlated with cancer immunity in both LUSC and LUAD.
- Prognostic meta-analyses showed negative correlations between IGF2BP2/3 and overall survival in LUAD, but not LUSC.
- GSEA revealed associations with VEGF in LUAD and matrix metallopeptidase activity in LUSC. High IGF2BP expression correlated with increased chemotherapy sensitivity.
Conclusions:
- IGF2BPs exhibit distinct roles and prognostic implications in LUAD and LUSC.
- The findings underscore the necessity for subtype-specific therapeutic strategies and prognostic biomarkers in lung cancer.
- Targeted therapies and prognostic tools should consider the unique molecular landscape of LUAD versus LUSC.
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