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Secretome-Based Identification of ULBP2 as a Novel Serum Marker for Pancreatic Cancer Detection.

Chang YT, Wu CC, Shyr YM, Chen TC, Hwang TL, Yeh TS, Chang KP, Liu HP, Liu YL, Tsai MH, Chang YS, Yu JS.

SourceGraduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan.

Abstract

BACKGROUND: To discover novel markers for improving the efficacy of pancreatic cancer (PC) diagnosis, the secretome of two PC cell lines (BxPC-3 and MIA PaCa-2) was profiled. UL16 binding protein 2 (ULBP2), one of the proteins identified in the PC cell secretome, was selected for evaluation as a biomarker for PC detection because its mRNA level was also found to be significantly elevated in PC tissues.

METHODS: ULBP2 expression in PC tissues from 67 patients was studied by immunohistochemistry. ULBP2 serum levels in 154 PC patients and 142 healthy controls were measured by bead-based immunoassay, and the efficacy of serum ULBP2 for PC detection was compared with the widely used serological PC marker carbohydrate antigen 19-9 (CA 19-9).

RESULTS: Immunohistochemical analyses revealed an elevated expression of ULPB2 in PC tissues compared with adjacent non-cancerous tissues. Meanwhile, the serum levels of ULBP2 among all PC patients (n = 154) and in early-stage cancer patients were significantly higher than those in healthy controls (p<0.0001). The combination of ULBP2 and CA 19-9 outperformed each marker alone in distinguishing PC patients from healthy individuals. Importantly, an analysis of the area under receiver operating characteristic curves showed that ULBP2 was superior to CA 19-9 in discriminating patients with early-stage PC from healthy controls.

CONCLUSIONS: Collectively, our results indicate that ULBP2 may represent a novel and useful serum biomarker for pancreatic cancer primary screening.

PMID:21625447[PubMed - in process] PMCID: PMC3098863Free PMC Article

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Figure 1Strategy for identification of potential PC serum biomarkers.(A), The strategy consists of cancer secretome and tissue tranacriptome analysis. (B), The proteins (50 µg) in CM and cell extracts (CE) of the cancer cells were resolved by 10% SDS-PAGE and stained with Coomassie blue (upper panel) or underwent immunoblot analysis with alpha-tubulin (lower panel). ...Secretome-Based Identification of ULBP2 as a Novel Serum Marker for Pancreatic Cancer DetectionPLoS One. ;6(5):e20029.Figure 2Elevated expression of BIGH3 and ULBP2 in PC tissues.(A), Immunohistochemical staining for BIGH3 (left panel) and ULBP2 (right panel) in paired pericancerous adjacent non-cancerous (lower panel) and tumor (upper panel) tissues. Scale bar, 100 µm. Original magnification, ×400. (B), Box-plot analysis of the immunohistochemical staining scores in paired ...Secretome-Based Identification of ULBP2 as a Novel Serum Marker for Pancreatic Cancer DetectionPLoS One. ;6(5):e20029.Figure 3Serum levels of BIGH3, ULBP2, and CA 19-9 in PC patients.The serum levels of BIGH3 (A), ULBP2 (B), and CA 19-9 © were measured in 154 pancreatic cancer patients (PC) and 142 healthy controls (Ctrl). Data are presented as Box plots. (D), ROC curve analyses of the ability of BIGH3, ULBP2, CA 19-9, and the two-marker panel comprising ULBP2 and CA 19-9 to d...Secretome-Based Identification of ULBP2 as a Novel Serum Marker for Pancreatic Cancer DetectionPLoS One. ;6(5):e20029.Figure 4Efficacy of ULBP2 and CA 19-9 for early detection of pancreatic cancer.Serum levels of ULBP2 (A) and CA 19-9 (B) in healthy controls (Ctrl) were compared with those in patients with early-stage PC. Data are presented as Box plots. ©, ROC curve analyses of the ability of ULBP2 (black line), CA 19-9 (dashed line), and a combination of both proteins (thick line) to disc...Secretome-Based Identification of ULBP2 as a Novel Serum Marker for Pancreatic Cancer DetectionPLoS One. ;6(5):e20029.

Figure 5ULBP2 levels in blood specimens from other cancers.(A), Serum ULBP2 levels in healthy controls (Ctrl) were compared to those in patients with nasopharyngeal carcinoma (NPC, n = 28) and colorectal carcinoma (CRC, n = 29). (B), Plasma ULBP2 levels in controls (Ctrl, n = 25) were compared to those in gastric cancer patients (GC, n = 30).Secretome-Based Identification of ULBP2 as a Novel Serum Marker for Pancreatic Cancer DetectionPLoS One. ;6(5):e20029.LinkOut - more resourcesFull Text SourcesPublic Library of SciencePubMed CentralPubMed Central CanadaUK PubMed Central

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