Assessment of importance of YKL-40 protein as biomarker in colorectal cancer and its relation to selected clinical and pathological parameters
More details
Hide details
Oddział Kliniczny Chirurgii Ogólnej, Kolorektalnej i Urazów Wielonarządowych, Wydział Nauk o Zdrowiu w Katowicach, Śląski Uniwersytet Medyczny w Katowicach
Zakład Pielęgniarstwa Chirurgicznego i Propedeutyki Chirurgii, Wydział Nauk o Zdrowiu w Katowicach, Śląski Uniwersytet Medyczny w Katowicach
Katedra i Zakład Biologii Medycznej i Molekularnej, Wydział Nauk Medycznych w Zabrzu, Śląski Uniwersytet Medyczny w Katowicach
Zakład Profilaktyki Chorób Żywieniowozależnych, Wydział Nauk o Zdrowiu w Bytomiu, Śląski Uniwersytet Medyczny w Katowicach
Klinika Chirurgii Wad Rozwojowych Dzieci i Traumatologii, Wydział Nauk Medycznych w Zabrzu, Śląski Uniwersytet Medyczny w Katowicach
Zakład Farmakologii Klinicznej, Wydział Nauk Medycznych w Zabrzu, Śląski Uniwersytet Medyczny w Katowicach
Dorota Nadbrzeżna-Barczyk   

Oddział Kliniczny Chirurgii Ogólnej, Kolorektalnej i Urazów Wielonarządowych, Wydział Nauk o Zdrowiu w Katowicach, Śląski Uniwersytet Medyczny w Katowicach
Ann. Acad. Med. Siles. 2021;75:136–146
Colorectal cancer (CRC) is one of the most common cancers in the world, accounting for 10% of the annual global cancer incidence. This malignant neoplasm can remain asymptomatic for a long time and, despite medical advances, is too frequently diagnosed too late. The YKL-40 protein is a growth factor that stimulates endothelial cell migration, and plays a role in inflammation and neoplasia. The aim of the study was to assess the significance of YKL-40 as a biomarker in CRC and to determine the correlation between the serum YKL-40 levels in CRC patients and selected clinical and pathological parameters.

Material and methods:
In a prospective study involving 133 patients over the age of 50, the serum YKL-40 protein level concentration was determined by the ELISA method. The patients were divided into two groups: 91 with CRC and 42 healthy. For the statistical analysis Student's t-test for independent data, the Mann-Whitney U test, and logistics regression were used.

The YKL-40 serum concentration was significantly higher in the CRC patients (163 ± 36 μg/l) than the healthy patients (54 ± 20 μg/l; p < 0.0001). There was a statistically significant difference in the serum YKL-40 concentration between the early and intermediate stages of CRC. There was no correlation between the clinical parameters, i.e. sex, age and BMI and the serum YKL-40 protein concentration in the people with CRC.

The YKL-40 protein seems to be a promising CRC biomarker. Its serum concentration is correlated with the stage of the cancer depending on the depth of the growth relative to the submucosa and may be a prognostic factor for an adverse prognosis of this cancer.

Labianca R., Nordlinger B., Beretta G.D., Mosconi S., Mandalà M., Cervantes A., Arnold D. Early colon cancer: ESMO Clinical Practise Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2013; 24 Suppl. 6: 64–72, doi: 10.1093/annonc/mdt354.
Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018; 68(6): 394–424, doi: 10.3322/caac.21492.
Amersi F., Agustin M., Ko C.Y. Colorectal cancer: epidemiology, risk factors, and health services. Clin. Colon Rectal Surg. 2005; 18(3): 133–140, doi: 10.1055/s-2005-916274.
OECD. Health at a Glance 2015: OECD Indicators. OECD Publishing. Paris 2015, doi: 10.1787/health_glance-2015-en.
Fleming M., Ravula S., Tatishchev S.F., Wang H.L. Colorectal carcinoma: pathologic aspects. J. Gastrointest. Oncol. 2012; 3(3): 153–173, doi: 10.3978/j.issn.2078-6891.2012.030.
Burch J.A., Soares-Weiser K., St John D.J.B., Duffy S., Smith S., Kleijnen J., Westwood M. Diagnostic accuracy of faecal occult blood tests used in screening for colorectal cancer: a systematic review. J. Med. Screen. 2007; 14(3): 132–137, doi: 10.1258/096914107782066220.
Schoen R.E., Pinsky P.F., Weissfeld J.L., Yokochi L.A., Church T., Laiyemo A.O. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N. Engl. J. Med. 2012; 366(25): 2345–2357, doi: 10.1056/NEJMoa1114635.
Johansen J.S., Schultz N.A., Jensen B.V. Plasma YKL-40: a potential new cancer biomarker? Future Oncol. 2009; 5(7): 1065–1082, doi: 10.2217/fon.09.66.
Hakala B.E., White C., Recklies A.D. Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J. Biol. Chem. 1993; 268(34): 25803–25810.
Johansen J.S., Høyer P.E., Larsen L.A., Price P.A., Møllgård K. YKL-40 protein expression in the early developing human musculoskeletal system. J. Histochem. Cytochem. 2007; 55(12): 1213–1228, doi: 10.1369/jhc.7A7245.2007.
Prakash M., Bodas M., Prakash D., Nawani N., Khetmalas M., Mandal A., Eriksson C. Diverse pathological implications of YKL-40: answers may lie in ‘outside-in’ signaling. Cell Signal. 2013; 25(7): 1567–1573, doi: 10.1016/j.cellsig.2013.03.016.
He C.H., Lee C.G., Dela Cruz C.S., Lee C.M., Zhou Y., Ahangari F. et al. Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2. Cell Rep. 2013; 4(4): 830–841, doi: 10.1016/j.celrep.2013.07.032.
Schultz N.A., Johansen J.S. YKL-40 – A protein in the field of transla-tional medicine: a role as a biomarker in cancer patients? Cancers 2010; 2(3): 1453–1491, doi: 10.3390/cancers2031453.
Recklies A.D., White C., Ling H. The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. Biochem. J. 2002; 365(Pt 1): 119–126, doi: 10.1042/BJ20020075.
Recklies A.D., Ling H., White C., Bernier S.M. Inflammatory cytokines induce production of CHI3L1 by articular chondrocytes. J. Biol. Chem. 2005; 280(50): 41213–41221, doi: 10.1074/jbc.M510146200.
Johansen J.S., Jensen B.V., Roslind A., Price P.A. Is YKL-40 a new therapeutic target in cancer? Expert Opin. Ther. Targets 2007; 11(2): 219–234, doi: 10.1517/14728222.11.2.219.
Cintin C., Johansen J.S., Christensen I.J., Price P.A., Sørensen S., Nielsen H.J. High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival. Cancer 2002; 95(2): 267–274, doi: 10.1002/cncr.10644.
Lequin R.M. Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA). Clin. Chem. 2005; 51(12): 2415–2418, doi: 10.1373/clinchem.2005.051532.
R Core Team. A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna 2018.
Kievit J., van de Velde C.J. Utility and cost of carcinoembryonic antigen monitoring in colon cancer follow-up evaluation: a Markov analysis. Cancer 1990; 65(11): 2580–2587.
Virgo K.S., Vernava A.M., Longo W.E., McKirgan L.W., Johnson F.E. Cost of patient follow-up after potentially curative colorectal cancer treatment. JAMA 1995; 273(23): 1837–1841.
Lucha P.A. Jr, Rosen L., Olenwine J.A., Reed J.F. 3rd, Riether R.D., Stasik J.J. Jr, Khubchandani I.T. Value of carcinoembryonic antigen monitoring in curative surgery for recurrent colorectal carcinoma. Dis. Colon Rectum 1997; 40(2): 145–149, doi: 10.1007/BF02054978.
Lee C.G., Hartl D., Lee G.R., Koller B., Matsuura H., Da Silva C.A. et al. Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis. J. Exp. Med. 2009; 206(5): 1149–1166, doi: 10.1084/jem.20081271.
Hanahan D., Coussens L.M. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012; 21(3): 309–322, doi: 10.1016/j.ccr.2012.02.022.
Johansen J.S., Lottenburger T., Nielsen H.J., Jensen J.E., Svendsen M.N., Kollerup G., Christensen I.J. Diurnal, weekly, and long-time variation in serum concentrations of YKL-40 in healthy subjects. Cancer Epidemiol. Biomarkers Prev. 2008; 17(10): 2603–2608, doi: 10.1158/1055-9965.EPI-07-2766.
Eurich K., Segawa M., Toei-Shimizu S., Mizoguchi E. Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells. World J. Gastroenterol. 2009; 15(42): 5249–5259, doi: 10.3748/wjg.15.5249.
Johansen J.S., Christensen I.J., Jørgensen L.N., Olsen J., Rahr H.B., Nielsen K.T. et al. Serum YKL-40 in risk assessment for colorectal cancer: A prospective study of 4496 subjects at risk of colorectal cancer. Cancer Epidemiol. Biomarkers Prev. 2015; 124(3): 621–626, doi: 10.1158/1055-9965.EPI-13-1281.
Chen C.C., Llado V., Eurich K., Tran H.T., Mizoguchi E. Carbohydrate-binding motif in chitinase 3-like 1 (CHI3L1/YKL-40) specifically activates Akt signaling pathway in colonic epithelial cells. Clin Immunol. 2011; 140(3): 268–275, doi: 10.1016/j.clim.2011.04.007.
Kawada M., Chen C.C., Arihiro A., Nagatani K., Watanabe T., Mizoguchi E. Chitinase 3-like-1 enhances bacterial adhesion to colonic epithelial cells through the interaction with bacterial chitin-binding protein. Lab. Invest. 2008; 88(8): 883–895, doi: 10.1038/labinvest.2008.47.
Matsui T., Yao T., Iwashita A. Natural history of early colorectal cancer. World J. Surg. 2000; 24(9): 1022–1028, doi: 10.1007/s002680010153.
Nowacki M. Rak jelita grubego. [W:] Onkologia kliniczna. T. 2. Red. M. Krzakowski, P. Potemski, K. Warzocha, P. Wysocki. Via Medica. Gdańsk 2015, s. 888–911.
Fuksiewicz M., Kotowicz B., Rutkowski A., Achinger-Kawecka J., Wagrodzki M., Kowalska M.M. The assessment of clinical usage and prognostic value of YKL-40 serum levels in patients with rectal cancer without distant metastasis. Technol. Cancer Res. Treat. 2018; 17: 1–8, doi: 10.1177/1533033818765209.
Shao R., Hamel K., Petersen L., Cao Q.J., Arenas R.B., Bigelow C. et al. YKL-40, a secreted glycoprotein, promotes tumor angiogenesis. Oncogene 2009; 28(50): 4456–4468, doi: 10.1038/onc.2009.292.
Faibish M., Francescone R., Bentley B., Yan W., Shao R. A YKL-40-neutralizing antibody blocks tumor angiogenesis and progression: a potential therapeutic agent in cancers. Mol. Cancer Ther. 2011; 10(5): 742–751, doi: 10.1158/1535-7163.MCT-10-0868.