Keshk Walaa Arafa, Zineldeen Doaa Hussein, Wasfy Rania E L-sayed, El-Khadrawy Osama Helmy
Department of Medical Biochemistry, Faculty of Medicine, Tanta University, El-Geish Street, Tanta, El-Gharbia, Egypt,
Med Oncol. 2014 Oct;31(10):192. doi: 10.1007/s12032-014-0192-4. Epub 2014 Aug 31.
Obesity is a major health problem which heightens the risk of several chronic illnesses including cancer development particularly colon cancer. The underlying pathophysiology of obesity associated colon cancer remains to be elucidated. The purpose of this current study was to determine fatty acid synthase (FASN) activity/expression, oxidized low-density lipoprotein (ox-LDL) level and redox status under the context of anthropometric measurements and lipid profile to find their potential role as interacting biomarkers relating obesity to colon cancer initiation and progression via nuclear factor kappa-B (NF-κB) signaling. This study was conducted upon Egyptian individuals; 30 obese subjects with colon cancer, 11 nonobese and 11 obese subjects without colon cancer. FASN gene expression, NF-κB immunoreactivity, and serum ox-LDL level were estimated by real-time PCR, immunohistochemistry and immunoassay, respectively. FASN activity, glycemic status, obesity, and oxidative stress indices were also assessed. It was found that FASN expression and activity were statistically increased in obese with colon cancer (P=0.021 and 0.018, respectively), with statistically significant increase in patients with advanced grading. Moreover, NF-κB immunoreactivity and serum ox-LDL level were significantly increased in obese colon cancer patients with significantly higher levels in those with advanced grading (all P<0.05). Dyslipidemia, insulin resistance, and oxidative stress indices were worsened in obese patients with colon cancer. These results revealed that FASN and ox-LDL as well as oxidative stress may increase the risk of obesity related colon cancer, particularly via NF-κB signaling and could be used as potential predictive and prognostic biomarkers for obesity complicated with colon cancer.
肥胖是一个主要的健康问题，它会增加多种慢性疾病的风险，包括癌症，尤其是结肠癌的发生风险。肥胖相关结肠癌的潜在病理生理学机制仍有待阐明。本研究的目的是在人体测量和血脂谱的背景下，确定脂肪酸合酶（FASN）活性/表达、氧化型低密度脂蛋白（ox-LDL）水平和氧化还原状态，以发现它们作为相互作用的生物标志物，通过核因子κB（NF-κB）信号传导将肥胖与结肠癌的发生和发展联系起来的潜在作用。本研究针对埃及个体进行；30名患有结肠癌的肥胖受试者、11名非肥胖受试者和11名无结肠癌的肥胖受试者。分别通过实时PCR、免疫组织化学和免疫测定法估计FASN基因表达、NF-κB免疫反应性和血清ox-LDL水平。还评估了FASN活性、血糖状态、肥胖和氧化应激指标。结果发现，患有结肠癌的肥胖者中FASN的表达和活性在统计学上有所增加（分别为P=0.021和0.018），在高级别分期的患者中增加具有统计学意义。此外，肥胖结肠癌患者的NF-κB免疫反应性和血清ox-LDL水平显著增加，在高级别分期患者中水平更高（所有P<0.05）。患有结肠癌的肥胖患者的血脂异常、胰岛素抵抗和氧化应激指标恶化。这些结果表明，FASN和ox-LDL以及氧化应激可能会增加肥胖相关结肠癌的风险，特别是通过NF-κB信号传导，并且可以用作肥胖合并结肠癌的潜在预测和预后生物标志物。
