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Potential prognostic biomarkers of pancreatic cancer.

ABSTRACT: We evaluated whether pancreatic main duct fluid can provide protein biomarkers with prognostic value.Mass spectrometry proteomics was applied to as little as 20µL of fluid collected at the time of tumor surgical resection. Biomarker proteins identified for 27 patients were correlated with clinical outcomes.Thirteen patients had pancreatic ductal adenocarcinomas, 4 had intraductal papillary mucinous neoplasm with in situ adenocarcinoma, 5 had ampullary adenocarcinomas, 2 had intraductal papillary mucinous neoplasms, and 3 had benign diseases. In pathologic stage II or higher pancreatic ductal adenocarcinoma, moderate or high expression of S100A8 or S100A9 proteins was associated with a median disease recurrence-free survival of 5.8 months compared with 17.3 months in patients with low expression (P = 0.002). Median overall survival was 12.6 versus 27 months for patients with moderate to high versus low S100A8 and A9 expression (P = 0.02).This analysis suggests distinct proteomic signatures for pancreatic cancer. Patients in our study with elevated levels of S100A8 or A9 in the ductal fluid, a near absence of pancreatic enzymes, and high levels of mucins were found to have significantly worse prognosis. Although further validation is needed to corroborate these findings, analysis of pancreatic ductal fluid is a promising tool for identifying biomarkers of interest.

SUBMITTER: Chen KT

PROVIDER: S-EPMC3859961 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Potential prognostic biomarkers of pancreatic cancer.

Chen Kathryn T KT Kim Phillip D PD Jones Kelly A KA Devarajan Karthik K Patel Bhavinkumar B BB Hoffman John P JP Ehya Hormoz H Huang Min M Watson James C JC Tokar Jeffrey L JL Yeung Anthony T AT

Pancreas 20140101 1

<h4>Objectives</h4>We evaluated whether pancreatic main duct fluid can provide protein biomarkers with prognostic value.<h4>Methods</h4>Mass spectrometry proteomics was applied to as little as 20µL of fluid collected at the time of tumor surgical resection. Biomarker proteins identified for 27 patients were correlated with clinical outcomes.<h4>Results</h4>Thirteen patients had pancreatic ductal adenocarcinomas, 4 had intraductal papillary mucinous neoplasm with in situ adenocarcinoma, 5 had amp ...[more]

PMID: 24326364

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Project description:BackgroundPancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDA), is an aggressive malignancy associated with a low 5-year survival rate. Poor outcomes associated with PDA are attributable to late detection and inoperability. Most patients with PDA are diagnosed with locally advanced and metastatic disease. Such cases are primarily treated with chemotherapy and radiotherapy. Because of the lack of effective molecular targets, early diagnosis and successful therapies are limited. The purpose of this study was to screen key candidate genes for PDA using a bioinformatic approach and to research their potential functional, pathway mechanisms associated with PDA progression. It may help to understand the role of associated genes in the development and progression of PDA and identify relevant molecular markers with value for early diagnosis and targeted therapy.Materials and methodsTo identify novel genes associated with carcinogenesis and progression of PDA, we analyzed the microarray datasets GSE62165, GSE125158, and GSE71989 from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and the Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A protein-protein interaction (PPI) network was constructed using STRING, and module analysis was performed using Cytoscape. Gene Expression Profiling Interactive Analysis (GEPIA) was used to evaluate the differential expression of hub genes in patients with PDA. In addition, we verified the expression of these genes in PDA cell lines and normal pancreatic epithelial cells.ResultsA total of 202 DEGs were identified and these were found to be enriched for various functions and pathways, including cell adhesion, leukocyte migration, extracellular matrix organization, extracellular region, collagen trimer, membrane raft, fibronectin-binding, integrin binding, protein digestion, and absorption, and focal adhesion. Among these DEGs, 12 hub genes with high degrees of connectivity were selected. Survival analysis showed that the hub genes (HMMR, CEP55, CDK1, UHRF1, ASPM, RAD51AP1, DLGAP5, KIF11, SHCBP1, PBK, and HMGB2) may be involved in the tumorigenesis and development of PDA, highlighting their potential as diagnostic and therapeutic factors in PDA.ConclusionsIn summary, the DEGs and hub genes identified in the present study not only contribute to a better understanding of the molecular mechanisms underlying the carcinogenesis and progression of PDA but may also serve as potential new biomarkers and targets for PDA.

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Potential prognostic biomarkers of pancreatic cancer.

Publications

Potential prognostic biomarkers of pancreatic cancer.

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