Abstract
YKL-40 is a mammalian member of the chitinase protein family. Although the function of YKL-40 is unknown, the pattern of its expression suggests a function in remodelling or degradation of extracellular matrix. High serum YKL-40 has been found in patients with recurrent breast cancer and has been related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three hundred and forty patients died. Sixteen per cent of the patients with Dukes' A, 26% with Dukes' B, 19% with Dukes' C and 39% with Dukes' D had high serum YKL-40 levels (adjusted for age). Analysis of serum YKL-40 as a continuous variable showed an association between increased serum YKL-40 and short survival (P < 0.0001). Patients with high preoperative serum YKL-40 concentration had significantly shorter survival than patients with normal YKL-40 (HR = 1.7; 95% CI: 1.3–2.1, P < 0.0001). Multivariate Cox analysis including serum YKL-40, serum CEA, Dukes' stage, age and gender showed that high YKL-40 was an independent prognostic variable for short survival (HR = 1.4; 95% CI: 1.1–1.8, P = 0.007). These results suggest that YKL-40 may play an important role in tumour invasion. © 1999 Cancer Research Campaign
Keywords: carcinoembryonic antigen, colorectal cancer, metastasis, tumour invasiveness, YKL-40/HC gp-39
Full Text
The Full Text of this article is available as a PDF (104.2 KB).
Footnotes
*YKL-40 has been named after its molecular weight (40 kDa) and the one letter code for its three N-terminal amino acids (Johansen et al, 1992). The protein is also called human cartilage glycoprotein-39 (HC gp-39) (Hakala et al, 1993)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bresalier R. S., Byrd J. C., Wang L., Raz A. Colon cancer mucin: a new ligand for the beta-galactoside-binding protein galectin-3. Cancer Res. 1996 Oct 1;56(19):4354–4357. [PubMed] [Google Scholar]
- DUKES C. E., BUSSEY H. J. The spread of rectal cancer and its effect on prognosis. Br J Cancer. 1958 Sep;12(3):309–320. doi: 10.1038/bjc.1958.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finlay I. G., McArdle C. S. Effect of occult hepatic metastases on survival after curative resection for colorectal carcinoma. Gastroenterology. 1983 Sep;85(3):596–599. [PubMed] [Google Scholar]
- Hu B., Trinh K., Figueira W. F., Price P. A. Isolation and sequence of a novel human chondrocyte protein related to mammalian members of the chitinase protein family. J Biol Chem. 1996 Aug 9;271(32):19415–19420. doi: 10.1074/jbc.271.32.19415. [DOI] [PubMed] [Google Scholar]
- Jass J. R., Love S. B., Northover J. M. A new prognostic classification of rectal cancer. Lancet. 1987 Jun 6;1(8545):1303–1306. doi: 10.1016/s0140-6736(87)90552-6. [DOI] [PubMed] [Google Scholar]
- Johansen J. S., Cintin C., Jørgensen M., Kamby C., Price P. A. Serum YKL-40: a new potential marker of prognosis and location of metastases of patients with recurrent breast cancer. Eur J Cancer. 1995;31A(9):1437–1442. doi: 10.1016/0959-8049(95)00196-p. [DOI] [PubMed] [Google Scholar]
- Johansen J. S., Hvolris J., Hansen M., Backer V., Lorenzen I., Price P. A. Serum YKL-40 levels in healthy children and adults. Comparison with serum and synovial fluid levels of YKL-40 in patients with osteoarthritis or trauma of the knee joint. Br J Rheumatol. 1996 Jun;35(6):553–559. doi: 10.1093/rheumatology/35.6.553. [DOI] [PubMed] [Google Scholar]
- Johansen J. S., Jensen H. S., Price P. A. A new biochemical marker for joint injury. Analysis of YKL-40 in serum and synovial fluid. Br J Rheumatol. 1993 Nov;32(11):949–955. doi: 10.1093/rheumatology/32.11.949. [DOI] [PubMed] [Google Scholar]
- Johansen J. S., Williamson M. K., Rice J. S., Price P. A. Identification of proteins secreted by human osteoblastic cells in culture. J Bone Miner Res. 1992 May;7(5):501–512. doi: 10.1002/jbmr.5650070506. [DOI] [PubMed] [Google Scholar]
- 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 Jun 1;65(11):2580–2587. doi: 10.1002/1097-0142(19900601)65:11<2580::aid-cncr2820651131>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
- Kirkpatrick R. B., Emery J. G., Connor J. R., Dodds R., Lysko P. G., Rosenberg M. Induction and expression of human cartilage glycoprotein 39 in rheumatoid inflammatory and peripheral blood monocyte-derived macrophages. Exp Cell Res. 1997 Nov 25;237(1):46–54. doi: 10.1006/excr.1997.3764. [DOI] [PubMed] [Google Scholar]
- Krause S. W., Rehli M., Kreutz M., Schwarzfischer L., Paulauskis J. D., Andreesen R. Differential screening identifies genetic markers of monocyte to macrophage maturation. J Leukoc Biol. 1996 Oct;60(4):540–545. doi: 10.1002/jlb.60.4.540. [DOI] [PubMed] [Google Scholar]
- 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 Feb;40(2):145–149. doi: 10.1007/BF02054978. [DOI] [PubMed] [Google Scholar]
- McArdle C. S., Hole D., Hansell D., Blumgart L. H., Wood C. B. Prospective study of colorectal cancer in the west of Scotland: 10-year follow-up. Br J Surg. 1990 Mar;77(3):280–282. doi: 10.1002/bjs.1800770314. [DOI] [PubMed] [Google Scholar]
- Morrison B. W., Leder P. neu and ras initiate murine mammary tumors that share genetic markers generally absent in c-myc and int-2-initiated tumors. Oncogene. 1994 Dec;9(12):3417–3426. [PubMed] [Google Scholar]
- Newland R. C., Chapuis P. H., Smyth E. J. The prognostic value of substaging colorectal carcinoma. A prospective study of 1117 cases with standardized pathology. Cancer. 1987 Aug 15;60(4):852–857. doi: 10.1002/1097-0142(19870815)60:4<852::aid-cncr2820600422>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
- Nyirkos P., Golds E. E. Human synovial cells secrete a 39 kDa protein similar to a bovine mammary protein expressed during the non-lactating period. Biochem J. 1990 Jul 1;269(1):265–268. doi: 10.1042/bj2690265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raz A., Zhu D. G., Hogan V., Shah N., Raz T., Karkash R., Pazerini G., Carmi P. Evidence for the role of 34-kDa galactoside-binding lectin in transformation and metastasis. Int J Cancer. 1990 Nov 15;46(5):871–877. doi: 10.1002/ijc.2910460520. [DOI] [PubMed] [Google Scholar]
- Rehli M., Krause S. W., Andreesen R. Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation. Genomics. 1997 Jul 15;43(2):221–225. doi: 10.1006/geno.1997.4778. [DOI] [PubMed] [Google Scholar]
- Royston P. Constructing time-specific reference ranges. Stat Med. 1991 May;10(5):675–690. doi: 10.1002/sim.4780100502. [DOI] [PubMed] [Google Scholar]
- Schoeppner H. L., Raz A., Ho S. B., Bresalier R. S. Expression of an endogenous galactose-binding lectin correlates with neoplastic progression in the colon. Cancer. 1995 Jun 15;75(12):2818–2826. doi: 10.1002/1097-0142(19950615)75:12<2818::aid-cncr2820751206>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
- Shackelton L. M., Mann D. M., Millis A. J. Identification of a 38-kDa heparin-binding glycoprotein (gp38k) in differentiating vascular smooth muscle cells as a member of a group of proteins associated with tissue remodeling. J Biol Chem. 1995 Jun 2;270(22):13076–13083. doi: 10.1074/jbc.270.22.13076. [DOI] [PubMed] [Google Scholar]
- Ståhle E., Glimelius B., Bergström R., Påhlman L. Preoperative prediction of outcome in patients with rectal and rectosigmoid cancer. Cancer. 1989 May 1;63(9):1831–1837. doi: 10.1002/1097-0142(19900501)63:9<1831::aid-cncr2820630929>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
- 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 Jun 21;273(23):1837–1841. [PubMed] [Google Scholar]
- Volck B., Price P. A., Johansen J. S., Sørensen O., Benfield T. L., Nielsen H. J., Calafat J., Borregaard N. YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils. Proc Assoc Am Physicians. 1998 Jul-Aug;110(4):351–360. [PubMed] [Google Scholar]
- Wiggers T., Arends J. W., Schutte B., Volovics L., Bosman F. T. A multivariate analysis of pathologic prognostic indicators in large bowel cancer. Cancer. 1988 Jan 15;61(2):386–395. doi: 10.1002/1097-0142(19880115)61:2<386::aid-cncr2820610231>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
- Wojciechowicz D. C., Park P. Y., Paty P. B. Beta 1-6 branching of N-linked carbohydrate is associated with K-ras mutation in human colon carcinoma cell lines. Biochem Biophys Res Commun. 1995 Jul 26;212(3):758–766. doi: 10.1006/bbrc.1995.2034. [DOI] [PubMed] [Google Scholar]
