Macrophage-capping protein as a tissue biomarker for prediction of response to gemcitabine treatment and prognosis in cholangiocarcinoma

Noriaki Morofuji, Hidenori Ojima, Hiroaki Onaya, Takuji Okusaka, Kazuaki Shimada, Yoshihiro Sakamoto, Minoru Esaki, Satoshi Nara, Tomoo Kosuge, Daisuke Asahina, Masahiko Ushigome, Nobuyoshi Hiraoka, Masato Nagino, Tadashi Kondo

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Cholangiocarcinoma is one of the deadliest malignancies worldwide. Recent studies reported that treatment with gemcitabine was effective in prolonging survival. However, as the treatment only benefited a limited subset of patients, selection of patients before treatment is required. To discover biomarkers predictive of the response to gemcitabine treatment in cholangiocarcinoma, we examined the proteome of three types of material resource; ten cell lines, nine xenografts and nine surgically resected primary tumors from patients who exhibited different response to gemcitabine treatment. Two-dimensional difference gel electrophoresis generated quantitative protein expression profiles including 3571 protein spots. We detected 172 protein spots with significant correlation with response to gemcitabine treatment. All proteins corresponding to these 172 protein spots were identified by mass spectrometry. We found that the macrophage-capping protein (CapG) was associated with response to gemcitabin treatment in all three types of material source. Immunohistochemical validation in an additional set of 196 cholangiocarcinoma cases revealed that CapG expression was associated with lymphatic invasion status and overall survival. Multivariate analysis showed that CapG protein expression was an independent prognostic factor for overall survival. In conclusion, CapG was identified as a novel candidate biomarker to predict response to gemcitabine treatment and survival in cholangiocarcinoma.

Original languageEnglish
Pages (from-to)1577-1589
Number of pages13
JournalJournal of Proteomics
Volume75
Issue number5
DOIs
Publication statusPublished - 2012 Feb 16
Externally publishedYes

Keywords

  • Biomarker
  • Cholangiocarcinoma
  • Gemcitabine
  • Macrophage-capping protein (CapG)
  • Two-dimensional difference gel electrophoresis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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