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Protein deep sequencing applied to biobank samples from patients with pancreatic cancer.

Abstract：

PURPOSE:Pancreatic cancer is commonly detected at advanced stages when the tumor is no longer amenable to surgical resection. Therefore, finding biomarkers for early stage disease is urgent. Here, we show that high-definition mass spectrometry (HDMS(E)) can be used to identify serum protein alterations associated with early stage pancreatic cancer. METHODS:We analyzed serum samples from patients with resectable pancreatic cancer, benign pancreatic disease, and healthy controls. The SYNAPT G2-Si platform was used in a data-independent manner coupled with ion mobility. The dilution of the samples with yeast alcohol dehydrogenase tryptic digest of known concentration allowed the estimated amounts of each identified protein to be calculated (Silva et al. in Anal Chem 77:2187-2200, 2005; Silva et al. in Mol Cell Proteomics 5:144-156, 2006). A global protein expression comparison of the three study groups was made using label-free quantification and bioinformatic analyses. RESULTS:Two-way unsupervised hierarchical clustering revealed 134 proteins that successfully classified pancreatic cancer patients from the controls, and identified 40 proteins that showed a significant up-regulation in the pancreatic cancer group. This discrimination reliability was further confirmed by principal component analysis. The differentially expressed candidates were aligned with protein network analyses and linked to biological pathways related to pancreatic tumorigenesis. Pancreatic disease link associations could be made for BAZ2A, CDK13, DAPK1, DST, EXOSC3, INHBE, KAT2B, KIF20B, SMC1B, and SPAG5, by pathway network linkages to p53, the most frequently altered tumor suppressor in pancreatic cancer. CONCLUSION:These pancreatic cancer study candidates may provide new avenues of research for a noninvasive blood-based diagnosis for pancreatic tumor stratification.

journal_name

J Cancer Res Clin Oncol

journal_title

Journal of cancer research and clinical oncology

authors

Ansari D,Andersson R,Bauden MP,Andersson B,Connolly JB,Welinder C,Sasor A,Marko-Varga G

doi

10.1007/s00432-014-1817-x

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

369-80

issue

2

eissn

0171-5216

issn

1432-1335

journal_volume

141

pub_type

杂志文章

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