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Background <p>The insulin-like growth factor (IGF) family plays a critical role in cancer progression, with the insulin-like growth factor-1 receptor IGF-1Rsignificantly regulating cellular growth through specific signaling pathways. These pathways may enhance cell proliferation and colorectal cancer (CRC) advancement. Some studies suggest an association between serum IGF levels and reduced CRC risk. To further elucidate this relationship, we conducted a systematic literature review and meta-analysis investigating the association between blood IGF levels and CRC onset.</p> Methods <p>A comprehensive search was conducted in PubMed, Scopus and Web of Science databases for studies published until February 15, 2025. A total of 71 eligible studies, comprising 7360 CRC cases and 15982 controls, were included. Gene expression data for IGF-1, IGF-1R, insulin receptor substrates (IRS1), IGF-2, and insulin-like growth factor-binding protein 3 (IGFBP3) were analyzed. The pooled effect estimates with 95% confidence intervals (CIs) were calculated to assess relationships between gene expression levels and CRC susceptibility. Statistical analyses were performed using STATA version 14.0 and R, version 4.4.1.</p> Results <p>The meta-analysis demonstrated a significant association between elevated circulating IGF-1 levels and an increased risk of colorectal cancer (WMD = 11.24; 95% CI: 4.18–18.30; <i>p</i> = 0.002) as well as precancerous colorectal lesions (WMD = 21.35; 99% CI: 3.37–34.89; <i>p</i> = 0.002). Conversely, reduced IGFBP-3 levels were significantly associated with a higher CRC risk (WMD = − 138.20; 95% CI: −231.77 to − 44.64; <i>p</i> = 0.004). No significant association was observed for IGF-2 (WMD = − 5.40; 95% CI: −35.11 to 24.31.</p> Conclusions <p>Elevated IGF1 levels and reduced IGFBP3 levels are correlated with increased CRC risk, suggesting a potential role of these factors in CRC development. These findings provide insight into CRC pathogenesis and could inform future diagnostic and therapeutic approaches.</p>

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Circulating protein levels of insulin-like growth factor 1 signaling pathway and the predisposition to colorectal carcinogenesis: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Fatemeh Naderi Noukabadi,
  • Elahe Daskar Abkenar,
  • Sascha Tierling,
  • Sajad Shojaee,
  • Sara Ashtari,
  • Amir Sadeghi,
  • Nayeralsadat Fatemi

摘要

Background

The insulin-like growth factor (IGF) family plays a critical role in cancer progression, with the insulin-like growth factor-1 receptor IGF-1Rsignificantly regulating cellular growth through specific signaling pathways. These pathways may enhance cell proliferation and colorectal cancer (CRC) advancement. Some studies suggest an association between serum IGF levels and reduced CRC risk. To further elucidate this relationship, we conducted a systematic literature review and meta-analysis investigating the association between blood IGF levels and CRC onset.

Methods

A comprehensive search was conducted in PubMed, Scopus and Web of Science databases for studies published until February 15, 2025. A total of 71 eligible studies, comprising 7360 CRC cases and 15982 controls, were included. Gene expression data for IGF-1, IGF-1R, insulin receptor substrates (IRS1), IGF-2, and insulin-like growth factor-binding protein 3 (IGFBP3) were analyzed. The pooled effect estimates with 95% confidence intervals (CIs) were calculated to assess relationships between gene expression levels and CRC susceptibility. Statistical analyses were performed using STATA version 14.0 and R, version 4.4.1.

Results

The meta-analysis demonstrated a significant association between elevated circulating IGF-1 levels and an increased risk of colorectal cancer (WMD = 11.24; 95% CI: 4.18–18.30; p = 0.002) as well as precancerous colorectal lesions (WMD = 21.35; 99% CI: 3.37–34.89; p = 0.002). Conversely, reduced IGFBP-3 levels were significantly associated with a higher CRC risk (WMD = − 138.20; 95% CI: −231.77 to − 44.64; p = 0.004). No significant association was observed for IGF-2 (WMD = − 5.40; 95% CI: −35.11 to 24.31.

Conclusions

Elevated IGF1 levels and reduced IGFBP3 levels are correlated with increased CRC risk, suggesting a potential role of these factors in CRC development. These findings provide insight into CRC pathogenesis and could inform future diagnostic and therapeutic approaches.