Dataset Information

Comparative serum proteomics of Intraductal papillary mucinous neoplasias and pacreatic adenocarcinoma

ABSTRACT: IPMN tumors are considered precancerous and starting from low grade dysplasia some of them develop IPMN associated or concomitant pancreatic cancer. The prognosis of IPMN is good if the tumor is operated before malignant transformation occurs. On the other hand, not nearly all IPMNs undergo malignant transformation during the patient’s life time. differences in proteins found in serum samples could provide a way to differentiate IPMNs with different states of dysplasia. The aim of our study was to compare the serum protein profiles in sera of patients with IPMN with low or high grade dysplasia, IPMN associated carcinoma and healthy controls. We have quantified 436 serum proteins with two or more unique peptides from 55 serum samples including 11 healthy controls. These proteomic dataset was analyzed with advanced multivariate statistical data analysis techniques to find the protein features which could be used as potential biomarkers of various grades of dysplasia as well as to differentiate dysplasia samples from pancreatic carcinoma.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

SUBMITTER: Sakari Joenväärä

LAB HEAD: Risto Renkonen

PROVIDER: PXD009139 | Pride | 2019-08-19

REPOSITORIES: Pride

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Project description:Purpose: The diagnosis of high grade intraductal papillary mucinous neoplasm (IPMN) is difficult to distinguish from low grade IPMN. The aim of this study was to identify potential markers for the discrimination of high grade and invasive IPMN from low and moderate grade IPMN. Experimental Design: Laser capture microdissection was used to isolate distinct foci of low grade, moderate grade, high grade, and invasive IPMN from paraffin embedded archival tissue from 14 patients who underwent resection for IPMN. Most samples included multiple grades in the same specimen. Affymetrix Human Exon microarrays were used for gene expression analysis to compare low and moderate grade (LMD) IPMN to high grade and invasive (HgInv) IPMN. Results: When comparing samples of LMD dysplasia (n=15) to those demonstrating HgInv (n=13), 62 genes were identified as showing significant changes in expression (p≤0.05 and a 2-fold cutoff), with up-regulation of 41 in HgInv IPMN and down-regulation in 21. Changes in gene expression are associated with biological processes related to malignant behavior including cell motion, cell proliferation, response to hypoxia, and epithelial to mesenchymal transition. Hierarchical clustering analysis demonstrated the ability of these 62 differentially expressed genes to distinguish between LMD and HgInv samples. In addition, altered signaling in several TGFβ-related pathways was exhibited in the progression of IPMN to malignancy. Conclusions: This study identifies a set genes associated with the progression of IPMN to malignancy. These genes are potential markers that could be used to identify IPMN requiring surgical resection. Using laser capture microdissection, distinct foci of low (n=10), moderate (n=5), and high grade dysplasia (n=6) as well as invasive carcinoma (n=7) were isolated from paraffin embedded archival tissue of 14 patients who underwent resection for IPMN. Gene expression data from Affymetrix Human Exon 1.0ST microarrays was utilized to compare low and moderate grade IPMN to high and invasive IPMN.