Abstract
Increasing evidence demonstrated that chitinase 3-like 1 (CHI3L1) was highly expressed and tightly associated with human tumor development and progression. However, its precise role in non-small cell lung cancer (NSCLC) remains to be delineated. The aim of this study was to examine CHI3L1 expression in patients with NSCLC and explore the relationship of CHI3L1 protein with clinicopathologic factors, tumor angiogenesis, and prognosis. CHI3L1 protein and intratumoral microvessels were examined by immunohistochemical staining in 95 NSCLC patients. Intratumoral microvessel density (MVD) was measured by counting CD34-positive immunostained endothelial cells. Quantitative real-time PCR (qRT-PCR) analyses were used to investigate the CHI3L1 expression status in tissues. Our result showed that CHI3L1 was significantly up-regulated in NSCLC tissues. In addition, univariate and multivariate analysis demonstrated that CHI3L1 protein overexpression and high MVD were significantly associated with tumor relapse. Although CHI3L1 overexpression and high MVD indicated poor overall survival (P < 0.05), multivariate analysis suggested that only CHI3L1 overexpression was an independent prognostic marker for unfavorable overall survival in patients with NSCLC (P < 0.05). The current results demonstrated that CHI3L1 may be a promising biomarker to identify individuals with poor prognostic potential and a possible target for anti-angiogenic therapy in patients with early stage NSCLC.
Similar content being viewed by others
References
Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61:212–36.
Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non small-cell lung cancer. N Engl J Med. 2002;346:92–8.
Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A. Changing epidemiology of small-cell lung cancer in the united states over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24(28):4539–44.
Fry WA, Philips JL, Menck HR. Ten-year survey of lung cancer treatment and survival in hospitals in the United States: a national cancer data base report. Cancer. 1999;86:1867–76.
Crino’ L, Weder W, van Meerbeeck J, Felip E, ESMO Guidelines Working Group. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011;21:v103–15.
Zivanović S, Rackov LP, Vojvodić D, Vucetić D. Human cartilage glycoprotein 39—biomarker of joint damage in knee osteoarthritis. Int Orthop. 2009;33(4):1165–70.
Lee IA, Kamba A, Low D, Mizoguchi E. Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease. World J Gastroenterol. 2014;20(5):1127–38.
Johansen JS, Milman N, Hansen M, Garbarsch C, Price PA, Graudal N. Increased serum YKL-40 in patients with pulmonary sarcoidosis—a potential marker of disease activity? Respir Med. 2005;99(4):396–402.
Nordenbaek C, Johansen JS, Halberg P, Wiik A, Garbarsch C, Ullman S, et al. High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement. Scand J Rheumatol. 2005;34(4):293–7.
Schiavon LL, Carvalho-Filho RJ, Narciso-Schiavon JL, Medina-Pestana JO, Lanzoni VP, Ferraz ML, et al. YKL-40 and hyaluronic acid (HA) as noninvasive markers of liver fibrosis in kidney transplant patients with HCV chronic infection. Scand J Gastroenterol. 2010;45(5):615–22.
Mitsuhashi A, Matsui H, Usui H, Nagai Y, Tate S, Unno Y, et al. Serum YKL-40 as a marker for cervical adenocarcinoma. Ann Oncol. 2009;20(1):71–7.
Shao R, Cao QJ, Arenas RB, Bigelow C, Bentley B, Yan W. Breast cancer expression of YKL-40 correlates with tumour grade, poor differentiation, and other cancer markers. Br J Cancer. 2011;105(8):1203–9.
Ushijima C, Tsukamoto S, Yamazaki K, Yoshino I, Sugio K, Sugimachi K. High vascularity in the peripheral region of non-small cell lung cancer tissue is associated with tumor progression. Lung Cancer. 2001;34(2):233–41.
Brock CS, Lee SM. Anti-angiogenic strategies and vascular targeting in the treatment of lung cancer. Eur Respir J. 2002;19(3):557–70.
Chaturvedi P, Gilkes DM, Takano N, Semenza GL. Hypoxia-inducible factor-dependent signaling between triple-negative breast cancer cells and mesenchymal stem cells promotes macrophage recruitment. Proc Natl Acad Sci U S A. 2014;111(20):E2120–9.
Tang H, Tian H, Yue W, Li L, Li S, Gao C, et al. Overexpression of LAPTM4B is correlated with tumor angiogenesis and poor prognosis in non-small cell lung cancer. Med Oncol. 2014;31(6):974.
S-h L, Tian H, Yue W-M, Li L, Li W-J, et al. Overexpression of metastasis-associated protein 1 is significantly correlated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer. Ann Surg Oncol. 2011;18:2048–56.
Vartanian RK, Weidner N. Endothelial cell proliferation in prostatic carcinoma and prostatic hyperplasia: correlation with Gleason’s score, microvessel density, and epithelial cell proliferation. Lab Investig. 1995;73(6):844–50.
Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, et al. The expression of the regulatory T cell-specific forkhead box transcription factor foxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res. 2005;11:8326–31.
Harving ML, Christensen LH, Ringsholt M, Lausten GS, Petersen MM. YKL-40 expression in soft-tissue sarcomas and atypical lipomatous tumors. An immunohistochemical study of 49 tumors. Acta Orthop. 2014;85(2):195–200.
Libreros S, Garcia-Areas R, Keating P, Carrio R, Iragavarapu-Charyulu VL. Exploring the role of CHI3L1 in “pre-metastatic” lungs of mammary tumor-bearing mice. Front Physiol. 2013;4:392.
Özdemir E, Çiçek T, Kaya MO. Association of serum YKL-40 level with tumor burden and metastatic stage of prostate cancer. Urol J. 2012;9(3):568–73.
Castellano I, Mistrangelo M, Crudo V, Chiusa L, Lupo R, Ricardi U, et al. YKL-40 expression in anal carcinoma predicts shorter overall and disease-free survival. Histopathology. 2009;55(2):238–40.
Urbich C, Kuehbacher A, Dimmeler S. Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res. 2008;79:581–8.
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding author
Additional information
Xiao-Wei Wang and Cheng-Liang Cai contributed equally to this work.
Rights and permissions
About this article
Cite this article
Wang, XW., Cai, CL., Xu, JM. et al. Increased expression of chitinase 3-like 1 is a prognosis marker for non-small cell lung cancer correlated with tumor angiogenesis. Tumor Biol. 36, 901–907 (2015). https://doi.org/10.1007/s13277-014-2690-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-014-2690-6