Transthyretin, identified by proteomics, is overabundant in pancreatic juice from pancreatic carcinoma and originates from pancreatic islets

Abstract

Analyses of pancreatic juice by proteomics have identified many proteins that are overabundant in pancreatic cancer (PC) juice. The mechanism by which secretion of these proteins occur remains unclear. Pancreatic juice was collected from patients with three pancreatic diseases: PC, chronic pancreatitis (CP), and simple choledocholithiasis (CDS), and analyzed by 2-DE, MALDI-TOF/MS, and Western blot. Five PC cell lines, 30 PC tissues and their corresponding adjacent pancreatic tissues were used to validate the expression of genes which code for overabundant proteins in PC juice. The mRNA and protein levels were measured by RT-PCR and immunohistochemistry, respectively. Using proteomics, it was demonstrated that the protein transthyretin (TTR) was upregulated more than 2-fold in PC juice compared with CP and CDS, while apolipoprotein A-I, lithostathine, and regenerating islet-derived 1 beta precursor were downregulated more than 2-fold. Western blots confirmed that TTR was overabundant in the PC juice. However, TTR mRNA was not detected in any of the five PC cell lines, and was only detected in islet cells. By microscopy, it was shown that islet architecture was almost completely destroyed, and the islet's maximum diameter appeared larger in PC tissues than in normal. Some overabundant proteins in PC juice, such as TTR expressed only in islets, leak into the pancreatic ductal system due to hyperplasia and architectural damage in PC tissues. The destruction of organ and tissue architecture by tumor growth may result in novel tumor markers even if the markers are not secreted directly by tumor cells.

Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9

“…Given that the majority of pancreatic cancers are believed to arise from ductal cells (or possibly acinar cells that undergo acinar-to-ductal metaplasia) [22,23], elevation of SYCN in the circulation may be a secondary effect of the growing tumor through local tissue destruction. In pancreatic cancer, this has been recently studied for the protein transthyretin (TTR), an islet cell protein that is elevated in pancreatic juice from pancreatic cancer patients through destruction of islet cell architecture in the presence of invasive cancer [24]. A similar mechanism of local tissue destruction causing increased release of the protein may be occurring with SYCN.…”

Transthyretin as a novel candidate biomarker for preeclampsia

“…In addition, >100 TTR mutations have been shown to be associated with amyloid diseases, which induce tissue-selective deposition of amyloid to various organs (12,13). In a previous study, TTR was shown to be upregulated by two-fold in pancreatic cancer, thus, it was concluded that TTR may be used as a novel tumor marker (14). However, whether TTR may be used as a biomarker of PE remains unknown.…”

Prognostic and Predictive Protein Biomarkers in Laryngeal Squamous Cell Carcinoma—A Systematic Review

“…Transthyretin has been shown to be a potential biomarker in pancreatic cancer [56] [57], but its association with multiple inflammatory disease processes may reduce its usefulness as a cancer biomarker [58]. Similarly, the use of fibrin and cofilin as LSCC biomarkers is limited by its non-specificity even though it is involved with various carcinogenic processes [59] [60].…”