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.
Subject(s)
Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Biomarkers, Tumor/metabolism , Carcinoma, Papillary/pathology , Cell Movement , Cell Proliferation , Chitinase-3-Like Protein 1/metabolism , Cholangiocarcinoma/pathology , Adult , Aged , Apoptosis , Bile Duct Neoplasms/metabolism , Bile Ducts, Intrahepatic/metabolism , Blotting, Western , Carcinoma, Papillary/metabolism , Case-Control Studies , Cell Adhesion , Cholangiocarcinoma/metabolism , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Survival Rate , Tumor Cells, CulturedABSTRACT
Tissue inflammation, certain cardiovascular syndromes and the occurrence of some solid tumors are correlated with raised serum concentrations of human chitinase-3-like protein 1 (YKL-40), a mammalian chitinase-like glycoprotein, which has become the subject of current research. Here we report the construction and characterization of an electrochemical platform for label-free immunosensing of YKL-40. Details of the synthesis of YKL-40 and production of anti-YKL-40 immunoglobulin G (IgG) are provided and cross-reactivity tests presented. Polyclonal anti-YKL-40 IgG was immobilized on gold electrodes and the resulting immunosensors were operated in an electrochemical flow system with capacitive signal generation. The strategy offered a wide linear detection range (0.1µg/L to 1mg/L) with correlation coefficients (R(2)) above 0.99 and good sensitivity (12.28±0.27nF/cm(2) per decade of concentration change). Additionally, the detection limit of 0.07±0.01µg/L was well below that of optical enzyme-linked immunosorbent assays (ELISAs), which makes the proposed methodology a promising alternative for YKL-40 related disease studies.
