Abstract
Solid pseudopapillary tumor of the pancreas (SPTP) is a low-grade malignant tumor with a favorable prognosis after surgery. Many previous studies have focused on clinical features or pathological biomarkers of the disease, but a better understanding of the molecular mechanisms underlying SPTP may help guide future therapeutic strategies. Here, we used isobaric tags for relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify differentially expressed proteins in SPTP specimens. A total of 1171 proteins with a threshold of a 1.5-fold change and a p value ≤ 0.05 between SPTP tissue and matched normal pancreas tissue were identified for bioinformatics analysis. Mass spectrometry results were then further confirmed by assessing six representative proteins (ACADL, EPHX2, MSI2, DKK4, JUP, and DAD1) in individual specimens with immunohistochemistry. Upon mapping of the differentially expressed proteins to the Kyoto Encyclopedia of Genes and Genomes pathways database, we found several new cell-adhesion molecules that could be used as pathologic biomarkers. Furthermore, we observed that many endoplasmic reticulum-associated proteins were altered, suggesting that endoplasmic reticulum stress may play an important role in SPTP tumorigenesis. Seven proteins (ERO1LB, TRIM1, GRP94, BIP, SEC61B, P4HB, and PDIA4) in this pathway were further validated by immunohistochemistry, and six of them (except SEC61B) coincided to the LC-MS/MS results. This first comprehensive analysis of the SPTP proteome confirms proteins that have been implicated in earlier reports and reveals novel candidates and pathways that could be investigated further for clinical applications.
Highlights
From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R
To identify differentially expressed proteins in Solid pseudopapillary tumor of the pancreas (SPTP) we performed a study based on the technology of Liquid Chromatography (LC)-MS/MS combined with Strong Cation Exchange (SCX)
The isobaric tags for relative and absolute quantitation (iTRAQ) labeled peptides were fractionated by SCX chromatography and the eluted fractions were analyzed by LC-MS/MS
Summary
From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. Solid pseudopapillary tumor of the pancreas (SPTP) is an uncommon epithelial neoplasm of low malignant potential that occurs predominantly in young women. The authors concluded that SPTP with incomplete capsules often presented with malignant behavior and hypothesized that SPTP was probably caused by disordered pancreatic stem cell development [6]. Another group at the University of Kiel analyzed 59 patients and postulated that SPTP might be derived from genital ridge/ovarian anlage-related cells [7]. The SPTP proteome has not yet been systemically analyzed
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