title: Macrophage-capping protein as a tissue biomarker for prediction of response to gemcitabine treatment and prognosis in cholangiocarcinoma.
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.
authors.affiliation: Division of Pharmacoproteomics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Morofuji
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ojima
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Onaya
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Esaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nara
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kosuge
authors.forename: Daisuke
authors.initials: D
authors.lastname: Asahina
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ushigome
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000368:Aged; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008840:Microfilament Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000096:biosynthesis*; D015996:Survival Rate; D014183:Transplantation, Heterologous; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D003841:Deoxycytidine; C066575:CAPG protein, human; D000093542:Gemcitabine