Secretome-based identification of ULBP2 as a novel serum marker for pancreatic cancer detection

PLoS One. 2011;6(5):e20029. doi: 10.1371/journal.pone.0020029. Epub 2011 May 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood*
  • Blotting, Western
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix Proteins / blood
  • GPI-Linked Proteins / blood
  • Gene Expression Profiling
  • Humans
  • Immunoassay
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / blood*
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / genetics
  • Transforming Growth Factor beta / blood

Substances

  • Biomarkers, Tumor
  • Extracellular Matrix Proteins
  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Transforming Growth Factor beta
  • ULBP2 protein, human
  • betaIG-H3 protein