Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas

Abstract

Solid-pseudopapillary neoplasm is an uncommon pancreatic tumor with distinct clinicopathologic features. Solid-pseudopapillary neoplasms are characterized by mutations in exon 3 of CTNNB1. However, little is known about the gene and microRNA expression profiles of solid-pseudopapillary neoplasms. Thus, we sought to characterize solid-pseudopapillary neoplasm-specific gene expression and identify the signaling pathways activated in these tumors. Comparisons of gene expression in solid-pseudopapillary neoplasm to pancreatic ductal carcinomas, neuroendocrine tumors, and non-neoplastic pancreatic tissues identified solid-pseudopapillary neoplasm-specific mRNA and microRNA profiles. By analyzing 1686 (1119 upregulated and 567 downregulated) genes differentially expressed in solid-pseudopapillary neoplasm, we found that the Wnt/b-catenin, Hedgehog, and androgen receptor signaling pathways, as well as genes involved in epithelial mesenchymal transition, are activated in solid-pseudopapillary neoplasms. We validated these results experimentally by assessing the expression of b-catenin, WIF-1, GLI2, androgen receptor, and epithelial-mesenchymal transitionrelated markers with western blotting and immunohistochemistry. Our analysis also revealed 17 microRNAs, especially the miR-200 family and miR-192/215, closely associated with the upregulated genes associated with the three pathways activated in solid-pseudopapillary neoplasm and epithelial mesenchymal transition. Our results provide insight into the molecular mechanisms underlying solid-pseudopapillary neoplasm tumorigenesis and its characteristic less epithelial cell differentiation than the other common pancreatic tumors.

Diagnosis and Management of Pancreatic Cystic Neoplasms

“…Recent gene expression profiling studies have demonstrated overactivation of the Wnt/b-catenin, hedgehog, and epithelial-to-mesenchymal transition signaling pathways in SPNs and may highlight new potential therapeutic targets for systemic disease. 69 …”

Distinct Protein Expression Profiles of Solid-Pseudopapillary Neoplasms of the Pancreas

“…Furthermore, among the up-regulated proteins, 24 (4.36% of 551 identified proteins) overlapped with the genes that were specifically up-regulated in SPNs on the mRNA array (1 119 genes, 3.6% of 31 334 genes from the mRNA array). 8 We evaluated the signaling pathways that were activated in SPNs according to the proteome data but did not find significant pathways. Therefore, we examined the expression of proteins involved in Wnt signaling, Hedgehog signaling, and androgen receptor signaling pathways, which we have previously reported as being activated in SPNs according to mRNA expression analysis.…”

Contribution of microRNA analysis to characterisation of pancreatic lesions: a review

“…Several papers have been based on a genome-wide analysis of miRNA expression of normal and lesional pancreatic specimens to distinguish expression signatures and associate this profile with diagnosis, prognosis or therapeutic interventions 16 17 21–24 26 29 30 38 39 42 45–48 54 62 69 75 78. It should be considered that a big limitation of microarray analysis is that the results need to be validated using a targeted technique, as qRT-PCR or ISH assays (see below).…”