Metabolic syndrome and colorectal cancer: is hyperinsulinemia/insulin receptor-mediated angiogenesis a critical process?
Metabolic syndrome and colorectal cancer: is hyperinsulinemia/insulin receptor-mediated angiogenesis a critical process?
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DOI：
10.1016/j.jgo.2013.11.004
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发表时间：
2014-01
影响因子：
3
通讯作者：
Extermann M
中科院分区：
文献类型：
--
作者：
Liu JJ;Druta M;Shibata D;Coppola D;Boler I;Elahi A;Reich RR;Siegel E;Extermann M
代谢综合征（MS）的组成部分与结直肠癌的风险和预后单独相关；然而，对主要机制的理解是缺乏的。前瞻性纳入21例可切除结直肠癌患者（10例多发性硬化症，11例非多发性硬化症）。根据世界卫生组织的标准对患者进行MS分类，并检测循环血管内皮生长因子（VEGF）、白细胞介素-6 （IL-6）、胰岛素样生长因子-1 （IGF-1）、空腹胰岛素和肿瘤中IGF-1受体（IGF-1R）、胰岛素受体（IR）和晚期糖基化终产物受体（RAGE）的表达。术后6个月复查循环标志物。MS组的基线和术后空腹胰岛素水平显著高于对照组（p < 0.001和0.003）。两组循环IL-6、VEGF、IGF-1及游离IGF-1无显著差异。免疫组化（IHC）结果显示，IGF-1R在肿瘤组织中的表达明显高于正常组织（p < 0.001），而IR的表达无显著差异。有趣的是，64%的肿瘤在肿瘤间质内或周围的血管中表现出高IR阳性，而在远离肿瘤的血管中则没有。逆转录聚合酶链反应（RT-PCR）证实肿瘤IGF-1R过表达（80%），但MS与非MS患者间无差异。67%的患者存在肿瘤RAGE过表达，两组间呈均匀分布。高胰岛素血症是区分结直肠癌患者与ms的唯一显著因素。肿瘤周围微血管中IR的优先过表达表明，高胰岛素血症可能通过促进血管生成来促进结直肠癌的生长。
Components of metabolic syndrome (MS) have been individually linked to colorectal cancer risk and prognosis; however, an understanding of the dominant mechanisms is lacking. Twenty-one patients (10 MS; 11 non-MS) with resectable colorectal cancer were prospectively enrolled. Patients were classified for MS by the World Health Organization criteria and tested for circulating vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), fasting insulin, and tumor expression of IGF-1 receptor (IGF-1R), insulin-receptor (IR) and receptor for advanced glycation end-products (RAGE). Circulating markers were re-tested 6 months after surgery. The MS group had significantly higher baseline and post-operative fasting insulin levels (p < 0.001 and 0.003). No differences were observed in circulating IL-6, VEGF, IGF-1 and free IGF-1. By immunohistochemistry (IHC), IGF-1R expression was significantly higher in tumor vs. normal tissues (p < 0.001) while IR expression showed no difference. Interestingly, 64% of tumors demonstrated high IR positivity in the vessels within or surrounding the tumor stroma, but not in the vessels away from the tumor. By reverse transcription polymerase chain reaction (RT-PCR), tumor IGF-1R over-expression (80%) was confirmed, but there was no difference between MS and non-MS patients. Tumor RAGE over-expression was found in 67% of patients and was equally distributed between the two groups. Hyperinsulinemia was the only significant factor distinguishing patients with colorectal cancer who have MS. The preferential over-expression of IR in the peri-tumoral microvessels suggests that hyperinsulinemia might contribute to colorectal cancer growth by enhancing angiogenesis.