Evaluation of Serum Levels of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor-Binding Protein 3 in Patients With Colorectal Cancer: A Case-Control Study

Rania Naguib, Mohamed Abouegylah, Sherif Sharkawy, Amel A Fayed, Hend Naguib, Rania Naguib, Mohamed Abouegylah, Sherif Sharkawy, Amel A Fayed, Hend Naguib

Abstract

Background/aim: Limited information is available about the relationship between colorectal cancer (CRC) and serum concentration of insulin-like growth factor 1 (IGF1) and insulin-like growth factor-binding protein 3 (IGFBP3). This study aims to compare the serum levels of IGF1and IGFBP3 in colorectal cancer cases and controls and to assess the relationship between their level and the demographic and histopathological characteristics.

Methods: A case-control study in which 50 patients with colorectal cancer and 50 controls matched by gender and age were compared regarding the demographic characteristics and the level of both IGF1 and IGFBP3. The correlation with different clinicopathological features was assessed.

Results: Levels of IGF1 were significantly higher while levels of IGFBP3 were significantly lower among cases compared to control. IGF1 was significantly higher among patients with liver metastasis, lymph node (LN) spread, and lymphovenous invasions and did not show significant association with gender, smoking status, family history, or primary site of colorectal cancer. Lower IGFBP3 was significantly high among patients with liver and lymph node metastasis, lymphovenous invasion, and patients with positive family history. This significant negative correlation was also detected between IGFBP3 levels and the size of the tumor.

Conclusions: High IGF1 levels and low concentrations of IGFBP3 are related to colorectal cancer and were significantly associated with liver metastasis, lymph node spread, and lymphovenous invasions. Further research is recommended to investigate if circulating IGF1 and IGFBP3 levels can be used to identify people at high risk of colorectal cancer and to investigate potential lifestyle or pharmaceutical ways to lower IGF1 bioactivity as a risk reduction strategy.

Keywords: case control studies; clinicopathological features; colorectal cancer; insulin-like growth factor binding protein 3; insulin-like growth factor1.

Conflict of interest statement

The authors have declared that no competing interests exist.

Copyright © 2021, Naguib et al.

Figures

Figure 1. Correlation between IGF1 with height…
Figure 1. Correlation between IGF1 with height in case groups (n = 50)
IGF1: insulin-like growth factor 1, r: correlation coefficient, p: probability
Figure 2. Correlation between IGFBP3 with age…
Figure 2. Correlation between IGFBP3 with age in case groups (n = 50)
IGFBP3: insulin-like growth factor binding protein 3, r: correlation coefficient, p: probability
Figure 3. Correlation between IGFBP3 with height…
Figure 3. Correlation between IGFBP3 with height in cases group (n = 50)
IGFBP3: insulin-like growth factor binding protein 3, r: correlation coefficient, p: probability
Figure 4. Correlation between IGFBP3 with size…
Figure 4. Correlation between IGFBP3 with size in cases group (n = 50)
IGFBP3: insulin-like growth factor binding protein 3, r: correlation coefficient, p: probability

References

    1. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. CA Cancer J Clin. 2018;68:394–424.
    1. Global patterns and trends in colorectal cancer incidence and mortality. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Gut. 2017;66:683–691.
    1. Insulin-like growth factor 2 (IGF2) signaling in colorectal cancer-from basic research to potential clinical applications. Kasprzak A, Adamek A. Int J Mol Sci. 2019;20:4915.
    1. IGF2 signaling and regulation in cancer. Brouwer-Visser J, Huang GS. Cytokine Growth Factor Rev. 2015;26:371–377.
    1. The insulin-like growth factor system in multiple myeloma: diagnostic and therapeutic potential. Bieghs L, Johnsen HE, Maes K, et al. Oncotarget. 2016;7:48732–48752.
    1. Insulin-like growth factor-related components and the risk of liver cancer in a nested case-control study. Adachi Y, Nojima M, Mori M, et al. Tumour Biol. 2016;37:15125–15132.
    1. Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies. Rinaldi S, Cleveland R, Norat T, et al. Int J Cancer. 2010;126:1702–1715.
    1. Clinicopathological significance and impact on outcomes of the gene expression levels of IGF-1, IGF-2 and IGF-1R, IGFBP-3 in patients with colorectal cancer: Overexpression of the IGFBP-3 gene is an effective predictor of outcomes in patients with colorectal cancer. Yamamoto N, Oshima T, Yoshihara K, et al. Oncol Lett. 2017;13:3958–3966.
    1. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Clayton PE, Banerjee I, Murray PG, Renehan AG. Nat Rev Endocrinol. 2011;7:11–24.
    1. Matrix metalloproteinase-7 triggers the matricrine action of insulin-like growth factor-II via proteinase activity on insulin-like growth factor binding protein 2 in the extracellular matrix. Miyamoto S, Nakamura M, Yano K, et al. Cancer Sci. 2007;98:685–691.
    1. Type I insulin-like growth factor receptor signaling in hematological malignancies. Vishwamitra D, George SK, Shi P, Kaseb AO, Amin HM. Oncotarget. 2017;8:1814–1844.
    1. Insulin-like growth factor (IGF) axis in cancerogenesis. Kasprzak A, Kwasniewski W, Adamek A, Gozdzicka-Jozefiak A. Mutat Res Rev Mutat Res. 2017;772:78–104.
    1. Cancer incidence in patients with acromegaly: a cohort study and meta-analysis of the literature. Dal J, Leisner MZ, Hermansen K, et al. J Clin Endocrinol Metab. 2018;103:2182–2188.
    1. Circulating levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 associate with risk of colorectal cancer based on serologic and Mendelian randomization analyses. Murphy N, Carreras-Torres R, Song M, et al. Gastroenterology. 2020;158:1300–1312.
    1. Specific metabolic biomarkers as risk and prognostic factors in colorectal cancer. Muc-Wierzgoń M, Nowakowska-Zajdel E, Dzięgielewska-Gęsiak S, et al. World J Gastroenterol. 2014;20:9759–9774.
    1. Circulating liver function markers and colorectal cancer risk: a prospective cohort study in the UK Biobank. He MM, Fang Z, Hang D, et al. Int J Cancer. 2021;148:1867–1878.
    1. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, Stampfer MJ. J Natl Cancer Inst. 1999;91:620–625.
    1. Circulating C-reactive protein concentrations and risks of colon and rectal cancer: a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Aleksandrova K, Jenab M, Boeing H, et al. Am J Epidemiol. 2010;172:407–418.
    1. Alterations in serum levels of insulin-like growth factors and insulin-like growth-factor-binding proteins in patients with colorectal cancer. el Atiq F, Garrouste F, Remacle-Bonnet M, Sastre B, Pommier G. Int J Cancer. 1994;57:491–497.
    1. IGF-1R, IGF-1 and IGF-2 expression as potential prognostic and predictive markers in colorectal-cancer. Peters G, Gongoll S, Langner C, et al. Virchows Arch. 2003;443:139–145.
    1. Expression of IGF-1 and IGF-1R and their relation to clinicopathological factors in colorectal cancer. Shiratsuchi I, Akagi Y, Kawahara A, et al. Anticancer Res. 2011;31:2541–2545.
    1. A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Giovannucci E, Pollak MN, Platz EA, et al. Cancer Epidemiol Biomarkers Prev. 2000;9:345–349.
    1. Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. Kaaks R, Toniolo P, Akhmedkhanov A, et al. J Natl Cancer Inst. 2000;92:1592–1600.
    1. Plasma insulin, IGF-binding proteins-1 and -2 and risk of colorectal cancer: a prospective study in northern Sweden. Palmqvist R, Stattin P, Rinaldi S, et al. Int J Cancer. 2003;107:89–93.
    1. IGF-1, IGF-2 and IGFBP-3 in prediagnostic serum: association with colorectal cancer in a cohort of Chinese men in Shanghai. Probst-Hensch NM, Yuan JM, Stanczyk FZ, Gao YT, Ross RK, Yu MC. Br J Cancer. 2001;85:1695–1699.
    1. A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women. Wei EK, Ma J, Pollak MN, Rifai N, Fuchs CS, Hankinson SE, Giovannucci E. Cancer Epidemiol Biomarkers Prev. 2005;14:850–855.

Source: PubMed

3
Subscribe