Bone Marrow Stromal Antigen 2 Is a Novel Plasma Biomarker and Prognosticator for Colorectal Carcinoma: A Secretome-Based Verification Study

Dis Markers. 2015:2015:874054. doi: 10.1155/2015/874054. Epub 2015 Oct 1.

Abstract

Background: The cancer cell secretome has been recognized as a valuable reservoir for identifying novel serum/plasma biomarkers for different cancers, including colorectal cancer (CRC). This study aimed to verify four CRC cell-secreted proteins (tumor-associated calcium signal transducer 2/trophoblast cell surface antigen 2 (TACSTD2/TROP2), tetraspanin-6 (TSPAN6), bone marrow stromal antigen 2 (BST2), and tumor necrosis factor receptor superfamily member 16 (NGFR)) as potential plasma CRC biomarkers.

Methods: The study population comprises 152 CRC patients and 152 controls. Target protein levels in plasma and tissue samples were assessed by ELISA and immunohistochemistry, respectively.

Results: Among the four candidate proteins examined by ELISA in a small sample set, only BST2 showed significantly elevated plasma levels in CRC patients versus controls. Immunohistochemical analysis revealed the overexpression of BST2 in CRC tissues, and higher BST2 expression levels correlated with poorer 5-year survival (46.47% versus 65.57%; p = 0.044). Further verification confirmed the elevated plasma BST2 levels in CRC patients (2.35 ± 0.13 ng/mL) versus controls (1.04 ± 0.03 ng/mL) (p < 0.01), with an area under the ROC curve (AUC) being 0.858 comparable to that of CEA (0.867).

Conclusion: BST2, a membrane protein selectively detected in CRC cell secretome, may be a novel plasma biomarker and prognosticator for CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / blood*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, Neoplasm / blood
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Cell Adhesion Molecules / blood
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • GPI-Linked Proteins / blood
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Humans
  • Nerve Tissue Proteins / blood
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Receptors, Nerve Growth Factor / blood
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism
  • Secretory Pathway
  • Tetraspanins / blood
  • Tetraspanins / genetics
  • Tetraspanins / metabolism

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • BST2 protein, human
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • GPI-Linked Proteins
  • NGFR protein, human
  • Nerve Tissue Proteins
  • Receptors, Nerve Growth Factor
  • TACSTD2 protein, human
  • TSPAN6 protein, human
  • Tetraspanins