Elevated levels of circulating osteopontin are associated with a poor survival after resection of cholangiocarcinoma

J Hepatol. 2017 Oct;67(4):749-757. doi: 10.1016/j.jhep.2017.06.020. Epub 2017 Jun 29.


Background & aims: Cholangiocarcinoma (CCA) represents a primary hepatic malignancy with incidence and mortality rising globally. Surgical treatment has remained the only potentially curative treatment option, but it is still unclear which patients benefit most from extended liver surgery, highlighting the need for new pre-operative stratification strategies. Osteopontin is a secreted extracellular glyco-phosphoprotein that has been associated with inflammation, metabolic disorders and cancer. Here, we examined the potential of circulating osteopontin serum levels as a diagnostic or prognostic biomarker in patients with CCA undergoing extended liver surgery.

Methods: Osteopontin expression levels were analysed in human and murine CCA tumour samples, using semi-quantitative reverse transcriptase PCR and immunohistochemistry. Osteopontin serum concentrations were measured by enzyme-linked immunosorbent assay in 107 patients with CCA undergoing elective tumour resection as well as 55 healthy controls. Results were correlated with clinical data.

Results: Correlating with an upregulation in CCA tumour cells and the tumour stroma, serum levels of osteopontin were elevated in patients with cholangiocarcinoma compared to healthy controls and patients with primary sclerosing cholangitis. Importantly, pre- and postoperative elevations of osteopontin showed a striking association with poor postoperative survival.

Conclusions: Serum osteopontin concentrations represent a promising prognostic biomarker in patients resectable CCA which could help to guide preoperative treatment decisions and to identify patients that will particularly benefit from extended liver surgery. Lay summary: Extended liver surgery is the only potentially curative treatment for patients with cholangiocarcinoma (CCA/biliary cancer), but it is currently unclear which patients benefit most from surgery. Detecting serum levels of osteopontin - a specific secreted glycoprotein involved in multiple human diseases - in CCA patients might help to identify those patients that particularly benefit from tumour resection.

Keywords: Biomarker; CA19-9; CCA; CEA; Cancer; Osteopontin; Prognosis.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Bile Duct Neoplasms / blood*
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / surgery
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Cholangiocarcinoma / blood*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / surgery
  • Cohort Studies
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Middle Aged
  • Osteopontin / blood*
  • Osteopontin / genetics
  • Osteopontin / metabolism
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism


  • Biomarkers, Tumor
  • RNA, Messenger
  • RNA, Neoplasm
  • SPP1 protein, human
  • Spp1 protein, mouse
  • Osteopontin