Kosti Adam, Harry Chen Hung-I, Mohan Sumathy, Liang Sitai, Chen Yidong, Habib Samy L
Department of Cellular & Structural Biology, University of Texas Health Science Center, San Antonio, Texas.
Department of Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas.
Genes Cancer. 2015 Jan;6(1-2):62-70. doi: 10.18632/genesandcancer.51.
Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have screened whole human DNA genome from healthy control, patients with diabetes or renal cell carcinoma (RCC) or RCC+diabetes. We found that 883 genes gain/163 genes loss of copy number in RCC+diabetes group, 669 genes gain/307 genes loss in RCC group and 458 genes gain/38 genes loss of copy number in diabetes group, after removing gain/loss genes obtained from healthy control group. Data analyzed for functional annotation enrichment pathways showed that control group had the highest number (280) of enriched pathways, 191 in diabetes+RCC group, 148 in RCC group, and 81 in diabetes group. The overlap GO pathways between RCC+diabetes and RCC groups showed that nine were enriched, between RCC+diabetes and diabetes groups was four and between diabetes and RCC groups was eight GO pathways. Overall, we observed majority of DNA alterations in patients from RCC+diabetes group. Interestingly, insulin receptor (INSR) is highly expressed and had gains in copy number in RCC+diabetes and diabetes groups. The changes in INSR copy number may use as a biomarker for predicting RCC development in diabetic patients.
我们实验室最近的研究表明,糖尿病患者患肾癌的风险更高。在当前研究中,我们对健康对照、糖尿病患者、肾细胞癌(RCC)患者或RCC合并糖尿病患者的全人类DNA基因组进行了筛查。我们发现,在去除从健康对照组获得的增减基因后,RCC合并糖尿病组有883个基因拷贝数增加/163个基因拷贝数减少,RCC组有669个基因拷贝数增加/307个基因拷贝数减少,糖尿病组有458个基因拷贝数增加/38个基因拷贝数减少。功能注释富集通路的数据分析表明,对照组富集通路数量最多(280个),糖尿病合并RCC组有191个,RCC组有148个,糖尿病组有81个。RCC合并糖尿病组与RCC组之间重叠的GO通路有9个富集,RCC合并糖尿病组与糖尿病组之间有4个,糖尿病组与RCC组之间有8个GO通路。总体而言,我们观察到RCC合并糖尿病组患者的DNA改变最多。有趣的是,胰岛素受体(INSR)在RCC合并糖尿病组和糖尿病组中高表达且拷贝数增加。INSR拷贝数的变化可用作预测糖尿病患者RCC发生的生物标志物。