Novel Blood Biomarkers of Pancreatic Cancer-Associated Diabetes Mellitus Identified by Peripheral Blood-Based Gene Expression Profiles
Novel Blood Biomarkers of Pancreatic Cancer-Associated Diabetes Mellitus Identified by Peripheral Blood-Based Gene Expression Profiles
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通过外周血基因表达谱鉴定胰腺癌相关糖尿病的新型血液生物标志物
DOI：
10.1038/ajg.2010.32
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发表时间：
2010-07-01
影响因子：
9.8
通讯作者：
Wu, Yu Lian
中科院分区：
文献类型：
--
作者：
Huang, Hai;Dong, Xin;Wu, Yu Lian
目的：胰腺癌的预后仍然很差，因此，在早期发现高危人群中胰腺癌的能力对于改善其长期生存至关重要。本研究的目的是探索能够区分胰腺癌相关糖尿病和2型糖尿病的特异性生物标志物，用于胰腺癌的早期检测。从2006年1月至2008年7月，收集了25例诊断为胰腺癌并糖尿病的患者，27例胰腺癌不伴糖尿病的患者，25例年龄> 5年的糖尿病患者和25例健康对照者。在微阵列实验中使用了32个样本，以寻找胰腺癌相关糖尿病特异性差异表达基因。对101份血液样本进行实时荧光定量PCR检测，进一步验证了方法的有效性。结果：通过基因芯片分析，我们发现58个基因在胰腺癌相关糖尿病患者中是独特的，其中23个基因表达上调，35个基因表达下调。通过RT-PCR进一步验证了11个上调基因，并选择其中的两个基因vanin-1（VNN1）和基质金属蛋白酶9（MMP 9）进行Logistic回归分析。VNN1和MMP9的组合显示出胰腺癌相关糖尿病与2型糖尿病的最佳区分。MMP 9和VNN1的蛋白表达与基因表达一致。结论：我们的研究结果表明，VNN1和MMP 9的组合可作为一种新的血液生物标志物面板用于区分胰腺癌相关的糖尿病2型糖尿病。
OBJECTIVES: The prognosis of pancreatic cancer is still very poor, and the ability to detect pancreatic cancer in high-risk groups at an early stage is therefore essential for improving its long-term survival. The purpose of this study was to explore specific biomarkers that can differentiate pancreatic cancer-associated diabetes from type 2 diabetes, for the early detection of pancreatic cancer.METHODS: From January 2006 to July 2008, 102 peripheral blood samples were collected from 25 patients diagnosed with pancreatic cancer and diabetes, 27 patients with pancreatic cancer without diabetes, 25 patients with diabetes mellitus >5 years, and 25 healthy controls. Thirty-two samples were used in microarray experiments to find differentially expressed genes specific for pancreatic cancer-associated diabetes. The results were further validated by quantitative real-time PCR for 101 blood samples. Protein expression of selected genes in serum and tissues was also detected.RESULTS: Using microarray analysis, we found 58 genes to be unique in patients with pancreatic cancer associated diabetes, including 23 upregulated genes and 35 downregulated genes. Eleven upregulated genes were further validated by RT-PCR, and two of these genes-vanin-1 (VNN1) and matrix metalloproteinase 9 (MMP9)-were selected for logistic regression analysis. The combination of VNN1 and MMP9 showed the best discrimination of pancreatic cancer-associated diabetes from type 2 diabetes. The protein expression of MMP9 and VNN1 was in accordance with the gene expression.CONCLUSIONS: Our results indicate that the combination of VNN1 and MMP9 may be used as a novel blood biomarker panel for the discrimination of pancreatic cancer-associated diabetes from type 2 diabetes.