Local IGFBP-3 MRNA Expression, Apoptosis and Risk of Colorectal Adenomas
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Background: IGF binding protein-3 (IGFBP-3) regulates the bioavailability of insulin-like growth factors I and II, and has both anti-proliferative and pro-apoptotic properties. Elevated plasma IGFBP-3 has been associated with reduced risk of colorectal cancer (CRC), but the role of tissue IGFBP-3 is not well defined. We evaluated the association between tissue or plasma IGFBP-3 and risk of colorectal adenomas or low apoptosis.
Methods: Subjects were consenting patients who underwent a clinically indicated colonoscopy at UNC Hospitals and provided information on diet and lifestyle. IGFBP-3 mRNA in normal colon was assessed by real time RT-PCR. Plasma IGFBP-3 was measured by ELISA and apoptosis was determined by morphology on H & E slides. Logistic regression was used to compute odds ratio (OR) and 95% confidence intervals.
Results: We observed a modest correlation between plasma IGFBP-3 and tissue IGFBP-3 expression (p = 0.007). There was no significant association between plasma IGFBP-3 and adenomas or apoptosis. Tissue IGFBP-3 mRNA expression was significantly lower in cases than controls. Subjects in the lowest three quartiles of tissue IGFBP-3 gene expression were more likely to have adenomas. Consistent with previous reports, low apoptosis was significantly associated with increased risk of adenomas (p = 0.003). Surprisingly, local IGFBP-3 mRNA expression was inversely associated with apoptosis.
Conclusion: Low expression of IGFBP-3 mRNA in normal colonic mucosa predicts increased risk of adenomas. Our findings suggest that local IGFBP-3 in the colon may directly increase adenoma risk but IGFBP-3 may act through a pathway other than apoptosis to influence adenoma risk.
Chen J, Zhuang W, Xia Y, Yin X, Tu M, Zhang Y PeerJ. 2023; 11:e15554.
PMID: 37397026 PMC: 10312159. DOI: 10.7717/peerj.15554.
Ding T, Peng Y, Hong C, Huang B, Liu C, Luo Y Discov Oncol. 2022; 13(1):128.
PMID: 36409444 PMC: 9679126. DOI: 10.1007/s12672-022-00591-1.
Aslan A, Erdem H, Akcay Celik M, Sahin A, Cankaya S Med Sci Monit. 2019; 25:5510-5517.
PMID: 31341157 PMC: 6676992. DOI: 10.12659/MSM.915335.
Clinical significance of serum IGFBP-3 in colorectal cancer.
Hou Y, Luo P, Ji G, Chen H J Clin Lab Anal. 2019; 33(6):e22912.
PMID: 31218761 PMC: 6642311. DOI: 10.1002/jcla.22912.
Molnar B, Galamb O, Peterfia B, Wichmann B, Csabai I, Bodor A BMC Cancer. 2018; 18(1):695.
PMID: 29945573 PMC: 6020382. DOI: 10.1186/s12885-018-4609-x.