Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma

Abstract

The non-neoplastic pancreatic parenchyma adjacent to infiltrating ductal adenocarcinoma demonstrates inflammation, fibrosis, acinar cell loss and small duct-like metaplasia of acinar cells. Similar morphologic changes are also observed in the setting of chronic pancreatitis. In addition, peritumoral acini have been shown to have alterations in gene expression even in the absence of morphological changes. To better understand the pancreatic acinar responses to infiltrating pancreatic ductal adenocarcinoma, we characterized gene expression patterns of pancreatic acinar tissue adjacent to infiltrating pancreatic ductal adenocarcinomas and compared them to gene expression patterns of acinar tissue affected by chronic pancreatitis as well as to those of normal pancreatic acini. Fresh-frozen pancreatic acinar tissue was microdissected from nine patients (three with pancreatic cancer, three with chronic pancreatitis, three with normal pancreata) using laser capture microdissection, and extracted RNA from each microdissection was subjected to two rounds of linear amplification and hybridized to oligonucleotide microarrays. Gene expression patterns were confirmed using quantitative RT-PCR and/or immunohistochemistry. A total of 20 genes was found to be overexpressed in peritumoral acinar tissue compared to normal acinar tissue and to acini affected by chronic pancreatitis. These 20 genes included pancreatitis-associated protein (HIP/PAP), a gene known to be overexpressed in acini adjacent to infiltrating pancreatic cancer, and the gene cartilage glycoprotein-39 (HC gp-39 or TKL-40). Serum HC gp-39 protein levels were significantly higher in patients with pancreatic cancer and in those with chronic pancreatitis than in controls without pancreatic disease. There was no significant difference in the levels of serum HC gp-39 in patients with pancreatic cancer and those with chronic pancreatitis. Our results demonstrate some of the molecular alterations in acinar cells that occur in response to adjacent infiltrating pancreatic ductal adenocarcinoma and reveal that such alterations can provide a rich source of markers of pancreatic cancer.

Reg3β Deficiency Impairs Pancreatic Tumor Growth by Skewing Macrophage Polarization

“…In addition, the use of microarrays allowed gene expression patterns to be characterized in pancreatic acinar tissue adjacent to infiltrating PDAC. The most abundantly expressed gene was Reg3b itself, which increased over 100-fold (35).…”

Protein Profiling of Microdissected Pancreas Carcinoma and Identification of HSP27 as a Potential Serum Marker

“…Despite enormous efforts, relevant markers useful for screening have been established in only a few tumor types (13,14 ), and no studies have found markers for early detection of pancreatic cancer (15)(16)(17)(18)(19). 2-DE, especially in combination with microdissection, seems an appropriate tool (19 ), but proteins in the peptide interval, as well as those of high hydrophobicity or of extreme isoelectric points, are difficult to separate and hence are typically neglected, resulting in a loss of potentially interesting proteins.…”

Evaluation of Topoisomerase IIa Expression in Pancreatic Ductal Adenocarcinoma: A Pilot Study Using Chromogenic in situ Hybridization and Immunohistochemistry on Tissue Microarrays

“…Previous studies have shown that the application of cDNA and TMAs for the detection of protein or gene alterations in human pancreatic non-neoplastic and cancer tissues is a reliable method of analysis [27][28][29][30] . Compared with their corresponding traditional larger sections, TMAs have been proven to provide concordant results in immunohistochemical studies, especially if they contain two or three cores from each case [31,32] .…”