Dysbindin as a novel biomarker for pancreatic ductal adenocarcinoma identified by proteomic profiling

Abstract

Pancreatic adenocarcinoma (PDAC) is known to have a poor prognosis partly because of lack of effective biomarkers. In the test set, we investigated dysbindin (DTNBP1) as a potential biomarker for PDAC by comparing preoperative and postoperative serum mass spectrometry (MS) proteomic profilings. Of the included 50 PDAC patients, 42 (positivity of 84.0%) detected a lower MS peak in postoperative serums than preoperative ones which was then identified as dysbindin. In the verification set, receiver operating characteristics (ROC) were used to assess diagnostic efficiency. 550 participants were included in the verification set [250 with PDAC, 80 with benign biliary obstruction (BBO), 70 with chronic pancreatitis (CP) and 150 healthy donors (HD)]. Dysbindin was increased in PDAC patient sera than in all controls. ROC curves revealed the optimum diagnostic cutoff for dysbindin was 699.16 pg/ml [area under curve (AUC) 0.849 (95% CI 0.812-0.885), sensitivity 81.9% and specificity 84.7%]. Raised concentration of dysbindin in sera could differentiate PDAC from BBO, CP and HD. Moreover, dysbindin maintained its diagnostic accuracy for PDAC patients who were CA19-9 negative [AUC 0.875 (95% CI 0.804-0.945), sensitivity 83.0%, specificity 89.0%] and for patients with benign biliary obstruction [AUC 0.849 (95% CI 0.803-0.894), sensitivity 82.3%, specificity 84.0%].Our discovery of dysbindin may complement measurement of CA19-9 in the diagnosis of PDAC and help to discriminate PDAC from other pancreatic diseases or begin biliary obstruction.

Analytically validated protein biomarkers of chronic pancreatitis and pancreatic cancer for potential clinical diagnosis with mass spectrometry

“…65 with AUC of 0.80 (sensitivity of 73.9% and specificity of 78.9). 68 The same team recently proved that dysbindin is an independent prognostic marker for PC. 71 Wu…”

“…Guo et al used offline 2D‐LC (size‐exclusion chromatography/reversed‐phase liquid chromatography (SEC‐RPLC)) coupled with MALDI‐TOF MS to screen the biomarker of pancreatic cancer in serum. They identified dysbindin (DTNBP1) as the potential protein biomarker for the discrimination of PC ( n = 250) from CP ( n = 70) with AUC of 0.80 (sensitivity of 73.9% and specificity of 78.9) . The same team recently proved that dysbindin is an independent prognostic marker for PC …”

Dysbindin facilitates invasion and metastasis by promoting phosphorylation of ERK in epithelial ovarian cancer

“…International Publisher and progression and significantly correlated with patients' prognosis. In a recent study, dysbindin showed significant correlation with pancreatic cancer and promoted tumor proliferation in vitro and in vivo [4,11]. Thus, improved knowledge of functions in dysbindin may help understand biology and provide optimal strategies in human cancers.…”

“…All the reactions were carried out in triplicate. The primers synthesized by Sangon Biotech were the following sequences which were reported previously [11]. The commonly used 2 -ΔΔCt method was performed to assess the target genes' expression [13].…”

“…To interfere with dysbindin expression, two different human dysbindin-targeting siRNA sequences, namely dysbindin-RNAi-1 and dysbindin-RNAi-2, were cloned to generate dysbindin-shRNA(s) with the sequences as previously reported [11] (synthesized by GenePharma). A scrambled shRNA was synthesized and inserted into dysbindin to generate the negative control.…”