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. 2023 Jan 20:2023:5145152.
doi: 10.1155/2023/5145152. eCollection 2023.

Differential Plasma Proteins Identified via iTRAQ-Based Analysis Serve as Diagnostic Markers of Pancreatic Ductal Adenocarcinoma

Xiubing Chen  1 , Xiaomin Liao  1 , Biaolin Zheng  1 , Feng Wang  1 , Feiran Chen  1 , Zhejun Deng  1 , Haixing Jiang  1 , Shanyu Qin  1
Affiliations

Differential Plasma Proteins Identified via iTRAQ-Based Analysis Serve as Diagnostic Markers of Pancreatic Ductal Adenocarcinoma

Xiubing Chen et al. Dis Markers. .

Abstract

Objective: We aimed to identify differentially expressed proteins in the plasma of patients with pancreatic cancer and control subjects, which could serve as potential tumor biomarkers.

Methods: Differentially expressed proteins were determined via isostatic labeling and absolute quantification (iTRAQ). Potential protein biomarkers were identified via enzyme-linked immunosorbent assay (ELISA) in 40 patients and 40 control subjects, and those eventually selected were further validated in 40 pancreatic cancer and normal pancreatic tissues.

Results: In total, 30 proteins displayed significant differences in expression among which 21 were downregulated and 9 were upregulated compared with the control group. ELISA revealed downregulation of peroxiredoxin-2 (PRDX2) and upregulation of alpha-1-antitrypsin (AAT), Ras-related protein Rab-2B (RAB2B), insulin-like growth factor-binding protein 2 (IGFBP2), Rho-related GTP-binding protein RhoC (RHOC), and prelamin-A/C (LMNA) proteins in 40 other samples of pancreatic cancer. Notably, only AAT, RAB2B, and IGFBP2 levels were consistent with expression patterns obtained with iTRAQ. Moreover, all three proteins displayed a marked increase in pancreatic cancer tissues. Data from ROC curve analysis indicated that the diagnostic ability of AAT, RAB2B, and IGFBP2 combined with carbohydrate antigen 19-9 (CA19-9) for pancreatic cancer was significantly greater than that of the single indexes (area under the curve (AUC): 90% vs. 75% (CA19-9), 76% (AAT), 71% (RAB2B), and 71% (IGFBP2), all P < 0.01).

Conclusion: AAT, RAB2B, and IGFBP2 could serve as effective biomarkers to facilitate the early diagnosis of pancreatic cancer.

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Conflict of interest statement

The authors have no competing interests to declare.

Figures

Figure 1
Figure 1
Differentially expressed plasma proteins in PDAC patients detected via iTRAQ.
Figure 2
Figure 2
Validation of six differentially expressed proteins in PDAC plasma with ELISA. Plasma levels of (a) AAT, (b) IGFBP2, (c) LMNA, (d) PRDX2, (e) RAB2B, and (f) RHOC in PDAC patients and normal controls. ∗∗∗P < 0.001 vs. control.
Figure 3
Figure 3
IHC detection of differential protein expression in PDAC tissue sections. (a) AAT levels in PDAC patients. (b) AAT levels in normal controls. (c) RAB2B levels in PDAC patients. (d) RAB2B levels in normal controls. (e) IGFBP2 levels in PDAC patients. (f) IGFBP2 levels in normal controls. (g) IHC integral analysis of AAT, RAB2B, and IGFBP2 in PDAC patients and normal controls.
Figure 4
Figure 4
Receiver operating characteristic (ROC) curves of the four indicators.
Figure 5
Figure 5
Validation of three differentially expressed proteins in early-stage PDAC plasma with ELISA. Plasma levels of (a) AAT, (b) RAB2B, and (c) IGFBP2 in early-stage PDAC patients and normal controls. ∗P < 0.05 vs. control.
Figure 6
Figure 6
Receiver operating characteristic (ROC) curves showed the diagnostic performance of AAT, RAB2B, and IGFBP2 as early-stage PDAC biomarkers individually or jointly.
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