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胰腺导管腺癌与相邻正常胰腺组织及胰腺良性囊腺瘤的蛋白质组学分析

Proteomic analysis of pancreatic ductal adenocarcinoma compared with normal adjacent pancreatic tissue and pancreatic benign cystadenoma.

作者信息

Cui Yazhou, Tian Mei, Zong Meijuan, Teng Mujian, Chen Yu, Lu Jun, Jiang Jinbo, Liu Xiaoyong, Han Jinxiang

机构信息

Key Laboratory of Ministry of Health for Biotech-Drug, Shandong Medicinal Biotechnology Center, Shandong Academy of Medical Sciences, Jinan, PR China.

出版信息

Pancreatology. 2009;9(1-2):89-98. doi: 10.1159/000178879. Epub 2008 Dec 12.

Abstract

BACKGROUND

Dual expression of potential biomarkers in both benign and malignant pancreatic tumors was a major obstacle in the development of diagnostic biomarkers of early pancreatic cancer.

METHODS

To better understand the limitations of potential protein biomarkers in pancreatic cancer, we employed two-dimensional difference gel electrophoresis technology and tandem mass spectrometry to study protein expression profiles in pancreatic cancer tissues, benign pancreatic adenoma and normal adjacent pancreas. Seven differently expressed proteins were selected for validation by Western blot and/or immunohistochemistry.

RESULTS

21 spots were overexpressed and 24 spots were downexpressed in pancreatic cancer compared with benign and normal adjacent tissues. Our study demonstrated that three candidate pancreatic ductal adenocarcinoma biomarkers identified in previous studies, fructose-bisphosphate aldolase A, alpha-smooth muscle actin and vimentin, were also overexpressed in pancreatic cystadenoma, which might lower their further utility as biomarkers for pancreatic cancer. Aflatoxin B(1) aldehyde reductase (AKR7A2) was confirmed to be only highly expressed in pancreatic cancer, not in normal adjacent pancreas and benign tumors.

CONCLUSIONS

The protein profile pattern of pancreatic cystadenoma was more similar to normal adjacent pancreas than pancreatic cancer. We identified panels of the upregulated proteins in pancreatic cancer, which have not been reported in prior proteomic studies. AKR7A2 may be a novel potential biomarker for pancreatic cancer.

摘要

背景

潜在生物标志物在胰腺良性和恶性肿瘤中均有表达,这是早期胰腺癌诊断生物标志物开发的主要障碍。

方法

为了更好地了解胰腺癌中潜在蛋白质生物标志物的局限性,我们采用二维差异凝胶电泳技术和串联质谱法研究胰腺癌组织、胰腺良性腺瘤和正常胰腺组织中的蛋白质表达谱。选择7种差异表达的蛋白质通过蛋白质印迹法和/或免疫组织化学法进行验证。

结果

与良性和正常相邻组织相比,胰腺癌中有21个斑点过表达,24个斑点低表达。我们的研究表明,先前研究中鉴定出的三种候选胰腺导管腺癌生物标志物,即果糖二磷酸醛缩酶A、α平滑肌肌动蛋白和波形蛋白,在胰腺囊腺瘤中也过表达,这可能会降低它们作为胰腺癌生物标志物的进一步应用价值。黄曲霉毒素B(1)醛还原酶(AKR7A2)被证实仅在胰腺癌中高表达,在正常相邻胰腺和良性肿瘤中不表达。

结论

胰腺囊腺瘤的蛋白质谱模式与正常相邻胰腺比与胰腺癌更相似。我们鉴定出了胰腺癌中上调的蛋白质组,这在先前的蛋白质组学研究中尚未报道。AKR7A2可能是一种新型的潜在胰腺癌生物标志物。

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