Abstract
BackgroundYKL-40 is a secreted inflammatory protein that its overexpression has been reported to correlate with poor outcome of various malignant diseases, especially in cancer. However, the function of this protein is still unclear.MethodsThe clinical prognosis of non-small cell lung cancers (NSCLC) patients and their clinical YKL-40 expressions were obtained from the Prognoscan database. The expressions of YKL-40 in patient samples were determined by Western Blotting assay. YKL-40 gene knockdown and overexpression were performed on NSCLC cancer cells (CL1-1 and CL1-5). The cells were investigated for their epithelial–mesenchymal transition (EMT) markers gene modulation through Western Blotting and RT-PCR. Further cell metastatic abilities were assessed by transwell migration and invasion assay.ResultIn this study, YKL-40 was observed to be highly expressed in NSCLC specimens. Furthermore, determined by the PrognoScan database analysis, patients with high expression levels of YKL-40 were found with poor prognosis. In the in vitro study, different characteristics of NSCLC cell lines (CL1-1, H23, H838, CL1-5, and H2009) were used as study models, where YKL-40 expression levels were determined to correlate with the phenotypic characteristics of cancer metastasis. In this study,YKL-40 was demonstrated to regulate EMT marker expressions such as Twist, Snail, Slug, N-cadherin, Vimentin, and E-cadherin. The protein’s affects in cancer cell migration and invasion were also observed in YKL-40 overexpression or knock down NSCLC cell lines.ConclusionAll of results from this study suggest that YKL-40 is a major factor in NSCLC metastasis. Thus, YKL-40 may serve as therapeutic targets for NSCLC patients in the future.
Highlights
YKL-40 is a secreted inflammatory protein that its overexpression has been reported to correlate with poor outcome of various malignant diseases, especially in cancer
YKL-40 was highly expressed in Non-small cell lung cancer (NSCLC) patients and was correlated with poor prognosis Several NSCLC patients were investigated in this study, where consistently higher expressions of YKL-40 were observed in tumor than in non-tumor cells (Fig. 1a)
These results were further confirmed through The Cancer Genome Atlas (TCGA) analysis, by comparing YKL-40 expression between normal and lung adenocarcinoma as well as lung squamous carcinoma populations
Summary
YKL-40 is a secreted inflammatory protein that its overexpression has been reported to correlate with poor outcome of various malignant diseases, especially in cancer. Non-small cell lung cancer (NSCLC) accounts for more than 80 % of lung cancers [1, 2]. Many genes have been found to be YKL-40, a member of mammalian chitinase-like proteins, is overexpressed in many pathological conditions that includes fibroblastic change in liver cirrhosis, increased deposition of connective tissue components and hyperplastic synovium in rheumatoid arthritis, and increased cellular infiltration as well as epithelial proliferation in chronic colitis [4]. YKL-40 is upregulated in many chronic inflammatory conditions such as inflamed tissues in ulcerative colitis, Crohn’s disease, rheumatoid arthritis, osteoarthritis, asthma, chronic
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