title: YKL-40/chitinase-3-like protein 1 is associated with poor prognosis and promotes cell growth and migration of cholangiocarcinoma.
abstract: YKL-40, a chitinase-like glycoprotein, is expressed at a high level in cancer patients. Its exact function is unknown and is the subject of current investigation. Here, we report the correlation of plasma YKL-40 levels with clinicopathological features of cholangiocarcinoma (CCA), a lethal bile duct cancer, particularly prevalent in Northeastern Thailand. Statistical analysis of plasma YKL-40 concentrations in 57 CCA patients and 41 normal healthy subjects gave a median value of 169.5 ng/mL for CCA patients compared with 46.9 ng/mL for the control subjects (P < 0.0001). There was no significant association of plasma YKL-40 levels with patient age, tumor grade, or histology type. However, Kaplan-Meier analysis suggested that the elevated plasma YKL-40 level was particularly associated with short survival in CCA patients (P = 0.038). Immunohistochemical examination of 34 CCA tissues revealed low expression of YKL-40 in CCA cells, but high expression in adjacent intratumoral stroma, liver, and connective tissues. Univariate analysis showed significant association of the intratumoral YKL-40 expression in CCA tissues with the non-papillary type CCA. Addition of rYKL-40 in the culture medium and transient expression of YKL-40 in CCA cell lines were shown to promote the growth and migration of the tumor cells, and that YKL-40 interacted with a cell-surface receptor involved in the Akt/Erk-mediated pathway. In conclusion, our results support the proposal of YKL-40 as a new candidate prognostic biomarker for cancer diseases.
authors.affiliation: Biochemistry-Electrochemistry Research Unit and School of Biochemistry, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand.
authors.forename: Sunisa
authors.initials: S
authors.lastname: Thongsom
authors.affiliation: Biochemistry-Electrochemistry Research Unit and School of Biochemistry, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand.
authors.forename: Wethaka
authors.initials: W
authors.lastname: Chaocharoen
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Atit
authors.initials: A
authors.lastname: Silsirivanit
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
authors.affiliation: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.affiliation: Bio-Medical Institute of Technology and Department of Physiology, University of Ulsan, Seoul, 138-736, South Korea.
authors.forename: Han
authors.initials: H
authors.lastname: Choe
authors.affiliation: Biochemistry-Electrochemistry Research Unit and School of Biochemistry, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand. wipa@sut.ac.th.|Center of Excellence on Advanced Functional Materials, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand. wipa@sut.ac.th.
authors.forename: Wipa
authors.initials: W
authors.lastname: Suginta
authors.affiliation: Biochemistry-Electrochemistry Research Unit and School of Biochemistry, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand. chutima.sub@sut.ac.th.
authors.forename: Chutima
authors.initials: C
authors.lastname: Talabnin
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D000071451:Chitinase-3-Like Protein 1 / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1
keywords: Chitinase-3-like protein 1; Cholangiocarcinoma; GH-18 glycosyl hydrolases; Prognostic marker; YKL-40