Thrombospondin-2 is a Highly Specific Diagnostic Marker and is Associated with Prognosis in Pancreatic Cancer
Thrombospondin-2 (TSP-2) has been reported as an early diagnostic marker for pancreatic ductal adenocarcinoma (PDAC) in Caucasian populations. This study was designed to validateTSP-2 as a diagnostic marker in a large Taiwan cohort and to investigate the association of TSP-2 with the clinical outcomes of PDAC patients.
The serum TSP-2 levels in 263 PDAC patients and 230 high-risk individuals (HRIs) were measured via an enzyme-linked immunosorbent assay. The sensitivity, specificity, and accuracy of TSP-2 as a diagnostic marker to discriminating PDAC patients from HRIs and correlations between TSP-2 levels and prognosis of PDAC patients were analyzed.
Serum TSP-2 levels were significantly higher in patients with PDAC (44.90 ± 40.70 ng/ml) than in the HRIs (17.52 ± 6.23 ng/ml). At a level of ≥ 29.8 ng/ml, TSP-2 exhibited 100% specificity, 55.9% sensitivity, 100% positive predictive value (PPV), and 66.5% negative predictive value (NPV) for discriminating PDAC patients from HRIs. The Cox regression analysis showed that higher serum TSP-2 levels were significantly associated with poor outcomes in PDAC patients (hazard ratio = 1.54, 95% confidence interval = 1.143–2.086, P = 0.005). Combining the carbohydrate antigen 19-9 (CA19-9) (cutoff value of 62.0 U/ml) and TSP-2 (cutoff value of 29.8 ng/ml) levels yielded 98.7% specificity, 90.5% sensitivity, 98.8% PPV, and 90.1% NPV for discriminating patients with PDAC from HRIs.
TSP-2 is a highly specific diagnostic marker and an independent prognostic marker in patients with PDAC. A combined biomarker panel, including TSP-2 and CA19-9, may facilitate future PDAC screening.
Taiwan Pancreas Foundation; MOST106-2321-B-002-033 and 107-2321-B-002-013.
Y-TC had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: H-YP, M-CC, C-MH, W-HL, and Y-TC. Acquisition, analysis, or interpretation of data: H-YP, M-CC, C-MH, H-IY, and Y-TC. Drafting of the manuscript: H-YP and Y-TC. Critical revision of the manuscript for important intellectual content: W-HL and Y-TC. Statistical analysis: H-YP, M-CC, and H-IY. Study supervision: W-HL and Y-TC.
All authors indicate no potential conflicts of interest.
- 4.Poruk KE, Gay DZ, Brown K, et al. The clinical utility of CA 19-9 in pancreatic adenocarcinoma: diagnostic and prognostic updates. Curr Mol Med. 2013;13(3):340–51.Google Scholar
- 10.WeilerGuettler H, Aird WC, Rayburn H, Husain M, Rosenberg RD. Developmentally regulated gene expression of thrombomodulin in postimplantation mouse embryos. Development. 1996;122(7):2271–81.Google Scholar
- 24.Chang MC, Wu CH, Yang SH, et al. Pancreatic cancer screening in different risk individuals with family history of pancreatic cancer-a prospective cohort study in Taiwan. Am J Cancer Res. 2017;7(2):357–69.Google Scholar
- 26.Kamochi J, Tokunaga T, Tomii Y, et al. Overexpression of the thrombospondin 2 (TSP2) gene modulated by the matrix metalloproteinase family expression and production in human colon carcinoma cell line. Oncol Rep. 2003;10(4):881–4.Google Scholar