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Insulin-like growth factor 2 mRNA-binding protein 2 is a therapeutic target in ovarian cancer
Jia Yuan1,2, Xin Li1,2, Fanchen Wang1,2
1Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai 201508, China.
Abstract:
Ovarian cancer (OC) is a fatal gynecologic disease. The most common treatment for OC patients is surgery combined with chemotherapy but most patients at advanced stages eventually develop relapse due to chemoresistance. This study examined the role and function of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in OC. We observed that the expression of IGF2BP2 mRNA and protein was up-regulated in OC cells and tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. An increase in IGF2BP2 expression at mRNA and protein levels was verified by the analyses of The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), respectively. Gene Expression Omnibus (GEO) and Cancer Cell Line Encyclopedia (CCLE) databases were applied to analyze the expression and clinical value of IGF2BP2. Gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses explored biological functions and the involvement of IGF2BP2 in cell growth. Indeed, the knockdown of IGF2BP2 resulted in the inhibition of OC cell proliferation evaluated by the Cell Counting Kit-8 assay. Genomic amplification of IGF2BP2 partly accounted for its overexpression. High expression of IGF2BP2 was associated with signal transducer and activator of transcription 1 (STAT1) and drug sensitivity and was correlated with an unfavorable survival outcome in OC patients. Furthermore, the responsiveness of chemotherapy and immunotherapy were analyzed using the "pRRophetic" R package and The Cancer Immune Atlas (TCIA) database, respectively. The low expression of IGF2BP2 was associated with chemoresistance but with high tumor microenvironment scores and tumor-infiltrating immune cells, suggesting that immunotherapy may apply in chemoresistant patients. The alteration of IGF2BP2 expression may respond to chemotherapy and immunotherapy. Thus, IGF2BP2 shows potential as a therapeutic target and diagnostic biomarker for OC.
Insights
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is overexpressed in ovarian cancer (OC), driving cell growth. Targeting IGF2BP2 may offer new therapeutic and diagnostic strategies for OC patients, potentially improving immunotherapy responses.
Area of Science:
- Gynecologic Oncology
- Molecular Biology
- Cancer Genomics
Background:
- Ovarian cancer (OC) is a leading cause of cancer death, with frequent relapse due to chemoresistance.
- Effective therapeutic targets and biomarkers for OC remain critical.
Purpose of the Study:
- To investigate the role and clinical significance of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in ovarian cancer.
- To evaluate IGF2BP2 as a potential therapeutic target and diagnostic biomarker for OC.
Main Methods:
- Quantitative real-time PCR and Western blot for IGF2BP2 expression analysis in OC tissues and cells.
- Analysis of TCGA, CPTAC, GEO, and CCLE databases for IGF2BP2 expression and clinical correlation.
- GSEA, KEGG, and GO analyses for functional exploration; Cell Counting Kit-8 assay for proliferation assessment.
- Bioinformatic analysis of chemoresistance and immunotherapy response using "pRRophetic" and TCIA.
Main Results:
- IGF2BP2 mRNA and protein expression were significantly upregulated in OC.
- IGF2BP2 overexpression, partly due to genomic amplification, correlated with poor survival and STAT1 expression.
- Knockdown of IGF2BP2 inhibited OC cell proliferation.
- Low IGF2BP2 expression was linked to chemoresistance but higher tumor immune infiltration, suggesting immunotherapy potential.
Conclusions:
- IGF2BP2 is a key driver of OC cell proliferation and is associated with unfavorable patient outcomes.
- IGF2BP2 expression levels may predict response to chemotherapy and immunotherapy.
- IGF2BP2 represents a promising therapeutic target and diagnostic biomarker for ovarian cancer.
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