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Tumor Biology

, Volume 37, Issue 7, pp 9451–9463 | Cite as

YKL-40/chitinase-3-like protein 1 is associated with poor prognosis and promotes cell growth and migration of cholangiocarcinoma

  • Sunisa Thongsom
  • Wethaka Chaocharoen
  • Atit Silsirivanit
  • Sopit Wongkham
  • Banchob Sripa
  • Han Choe
  • Wipa Suginta
  • Chutima Talabnin
Original Article

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.

Keywords

Chitinase-3-like protein 1 Cholangiocarcinoma GH-18 glycosyl hydrolases Prognostic marker YKL-40 

Abbreviations

pAkt

Phosphorylated (active) AKT/PKB (protein kinase B) kinase

BSA

Bovine serum albumin

CCA

Cholangiocarcinoma

pERK

Phosphorylated (active) extracellular signal-regulated kinase

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

HRP

Horseradish peroxidase

PBS

Phosphate-buffered saline

PBST

Phosphate-buffered saline tween

rpm

Revolutions per minute

Notes

Acknowledgments

We thank the Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, for participating in collection of patient data and tumor samples. We would like to acknowledge Biochemistry Laboratory, the Center for Scientific and Technological Equipment, Suranaree University of Technology, for providing all research facilities. We greatly appreciate a critical proofreading of this manuscript by Dr. David Apps, Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, United Kingdom.

Authors’ contributions

ST carried out all the experiments, performed data analysis, and prepared the manuscript draft. WC generated the human CHI3L1 construct. AS, SW, and BS provided patients’ plasma samples and paraffin-embedded tissues and clinical data related to the CCA patients. HC provided guidance on Transwell migration assay. WS was a grant holder, conceived the idea of research, provided advice on gene isolation, cloning, expression, and purification of rYKL-40, and revised and approved the manuscript. CT coordinated cancer studies, provided guidance on statistical analyses, immunohistochemistry, cell proliferation, and migration assays, and took part in manuscript preparation.

Compliance with ethical standards

Written informed consent was obtained from all patients. The study has been approved by the Ethics Committee for Human Research, Suranaree University of Technology (EC-55-17).

Funding

This work is financially supported by The Thailand Research Fund through the Royal Golden Jubilee (RGJ) Ph.D. Program (PHD/0054/2551) to ST and WS. WS and CS were also funded by Suranaree University of Technology (grant numbers SUT1-102-54-36-06 and SUT1-102-56-12-32).

Conflicts of interest

None

Supplementary material

13277_2016_4838_MOESM1_ESM.doc (28 kb)
Fig. S1 (DOC 27 kb)
13277_2016_4838_MOESM2_ESM.doc (70 kb)
Fig. S2 (DOC 70 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Sunisa Thongsom
    • 1
  • Wethaka Chaocharoen
    • 1
  • Atit Silsirivanit
    • 2
  • Sopit Wongkham
    • 2
  • Banchob Sripa
    • 3
  • Han Choe
    • 4
  • Wipa Suginta
    • 1
    • 5
  • Chutima Talabnin
    • 1
  1. 1.Biochemistry-Electrochemistry Research Unit and School of BiochemistrySuranaree University of TechnologyNakhon RatchasimaThailand
  2. 2.Department of Biochemistry, Faculty of Medicine, Liver Fluke and Cholangiocarcinoma Research CenterKhon Kaen UniversityKhon KaenThailand
  3. 3.Department of Pathology, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand
  4. 4.Bio-Medical Institute of Technology and Department of PhysiologyUniversity of UlsanSeoulSouth Korea
  5. 5.Center of Excellence on Advanced Functional MaterialsSuranaree University of TechnologyNakhon RatchasimaThailand

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