iTRAQ-based quantitative proteomics reveals myoferlin as a novel prognostic predictor in pancreatic adenocarcinoma.
UNLABELLED
Histological differentiation is a major pathological parameter associated with poor prognosis in patients with pancreatic adenocarcinoma (PAC) and the molecular signature underlying PAC differentiation may involve key proteins potentially affecting the malignant characters of PAC. We aimed to identify the proteins which could be implicated in PAC prognosis. We used isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography-tandem mass spectrometry to compare protein expression in PAC tissues with different degrees of histological differentiation. A total of 1623 proteins were repeatedly identified by performing the iTRAQ-based experiments twice. Of these, 15 proteins were differentially expressed according to our defined criteria. Myoferlin (MYOF) was selected to validate the proteomic results by western blotting. Immunohistochemistry in a further 154 PAC cases revealed that myoferlin significantly correlated with the degree of histological differentiation (P=0.004), and univariate and multivariate analyses indicated that MYOF is an independent prognostic factor for survival (hazard ratio, 1.540; 95% confidence interval, 1.061-2.234; P=0.023) of patients with PAC after curative surgery. RNA interference-mediated knockdown of MYOF alleviated malignant phenotypes of both primary and metastatic PAC cell lines in vitro and in vivo. Thus, ITRAQ-based quantitative proteomics revealed the prognostic value of MYOF in PAC.


BIOLOGICAL SIGNIFICANCE
Our results provide the possibility of novel strategies for pancreatic adenocarcinoma management.
['Wang|Wan-Sheng|WS|', 'Liu|Xiao-Hui|XH|', 'Liu|Ling-Xiao|LX|', 'Lou|Wen-Hui|WH|', 'Jin|Da-Yong|DY|', 'Yang|Peng-Yuan|PY|', 'Wang|Xiao-Lin|XL|']
D000230:Adenocarcinoma D000368:Aged D000818:Animals D017209:Apoptosis D002135:Calcium-Binding Proteins D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D008565:Membrane Proteins D051379:Mice D008807:Mice, Inbred BALB C D008875:Middle Aged D009124:Muscle Proteins D009368:Neoplasm Transplantation D010190:Pancreatic Neoplasms D010641:Phenotype D011379:Prognosis D040901:Proteomics D034622:RNA Interference
Proteomics Myoferlin Prognosis iTRAQ Pancreatic neoplasms