Preoperative serum YKL-40 is a marker for detection and prognosis of endometrial cancer

Gynecologic Medical Oncology, Department of Medicine, Howard 903, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Gynecologic Oncology (Impact Factor: 3.77). 02/2007; 104(2):435-42. DOI: 10.1016/j.ygyno.2006.08.028
Source: PubMed


YKL-40 is a secreted glycoprotein of the chitinase family that has been previously described as a diagnostic and prognostic marker for a number of cancers, including epithelial ovarian cancer. In this study, we examined the frequency of serum elevation as well as the diagnostic and prognostic significance of this serum marker in endometrial cancer.
Preoperative serum levels of YKL-40 and CA125 were evaluated by enzyme-linked immunosorbent assay (ELISA) for all endometrial cancer patient samples (34) available in the Memorial Sloan-Kettering Cancer Center Gynecology Service Tissue Bank between the years 1987 and 2002, and compared to a cohort of normal individuals. A YKL-40 value of 61 ng/mL has previously been determined to represent the upper limit of normal. YKL-40 values were correlated with clinical characteristics, including patient age, tumor grade, histology, clinical stage, and clinical outcome (progression-free survival [PFS] and overall survival [OS]).
YKL-40 was elevated (>61 ng/mL) in 26 (76%) of 34 endometrial cancer patients compared with elevations of CA125 in 21 (62%) of 34 patients (P=0.09). Twenty-eight (82%) of all 34 patients had elevations of either CA125 or YKL-40 or both; 16 (89%) of 18 advanced-stage endometrial cancer patients had elevation of at least one of these two markers. Median preoperative YKL-40 value was 137 ng/mL (range, 22-1738 ng/mL) for endometrial cancer patients compared with 28 ng/mL (range, 15-72 ng/mL) for normal healthy subjects (P<0.0001). There was no statistically significant association of YKL-40 with patient age, tumor grade, histology, or stage. Elevation of YKL-40 (>80 ng/mL) was correlated with poor clinical outcome in univariate analysis, but was not demonstrated in multivariate analysis. At 5 years' follow-up, the PFS rate was 80% for patients with YKL-40<80 ng/mL compared with 43% for patients with YKL-40>80 ng/mL (P=0.004). The 5-year OS rate for patients with YKL-40<80 ng/mL was 79% compared with 48% for patients with YKL-40>80 ng/mL (P=0.047).
Preoperative serum YKL-40 is frequently elevated and may represent a novel marker for the detection of endometrial cancer and the identification of high-risk subsets of patients with worse clinical outcome. Further investigation of this promising endometrial cancer marker in larger studies is warranted.

8 Reads
  • Source
    • "Recently, YKL-40 was reported to be highly expressed in several types of cancers, including ovarian cancer [15], breast cancer [16], lung cancer [17], hepatocellular carcinoma [18], and glioblastoma [19]. In addition, serum YKL-40 has been suggested as a potential biomarker for the diagnosis and monitoring of these cancers [20-24]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Elevated serum YKL-40 levels have been observed in various cancers. We evaluated the diagnostic performance of serum YKL-40 alone or in combination with the CEA, CYFRA21-1 and SCCA tumor markers for patients with esophageal squamous cell carcinoma (ESCC). Methods YKL-40 was detected in ESCC cell lines and tissues by real-time RT-PCR, Western blotting and ELISA. YKL-40 protein expression was determined in 20 ESCC tumor tissues using immunohistochemistry. Serum YKL-40 was measured by ELISA in 126 healthy donors, 59 patients with benign esophageal diseases and 150 patients with ESCC. Serum CEA, CYFRA21-1 and SCCA were determined by electrochemiluminescence. Results YKL-40 mRNA and protein were observed in ESCC cancer cell lines, tissues and cell culture media, respectively. YKL-40 expression was observed in 17 of 20 ESCC samples (85%). Serum YKL-40 concentration was significantly elevated in patients with ESCC (Range: 6.95-502.10 ng/ml) compared with patients with benign diseases (Range: 1.21-429.30 ng/ml; P = 0.038) and healthy controls (Range: 2.56-132.26 ng/ml; P < 0.001). ROC curves demonstrated that serum YKL-40 has a sensitivity of 72.70%, a specificity of 84.13% and an AUC of 0.874 for the diagnosis of ESCC, which was superior to CEA (Sen: 8.00%; Spe: 96.80%, AUC = 0.652), CYFRA21-1 (Sen: 40.00%; Spe: 92.06%, AUC = 0.746) and SCCA (Sen: 32.67%; Spe: 94.44%, AUC = 0.789). The YKL-40 and SCCA combination was better for diagnosing ESCC (Sen: 82.00%, Spe: 79.37%, PPV: 82.55 and NPV: 78.74; AUC = 0.917) than the YKL-40 and CEA combination (Sen: 74.00%, Spe: 83.20%, PPV: 84.09 and NPV: 72.73; AUC = 0.877), the YKL-40 and CYFRA21-1 combination (Sen: 82.00%, Spe: 77.78%, PPV: 81.46% and NPV: 78.40%; AUC = 0.897) or the CEA, CYFRA21-1 and SCCA combination (Sen: 56.67%, Spe: 84.80%, PPV: 81.73 and NPV: 61.99; AUC = 0.831). Associations between serum YKL-40 levels and the clinic characteristics of ESCC were not significant, with the exception of age (p = 0.001). Conclusions ESCC tumor cells and tissues express YKL-40. Serum YKL-40 may be a potential biomarker for ESCC. Serum YKL-40 in combination with SCCA significantly increases the sensitivity of detecting ESCC.
    BMC Cancer 07/2014; 14(1):490. DOI:10.1186/1471-2407-14-490 · 3.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chitinases (EC, which hydrolyze β-1,4-glucosidic bonds of chitin are widely distributed in the biological word and have received an increased attention during the last two decades due to their wider range of biotechnological applications specially in the agricultural, medical, industrial and environmental fields. To improve the chitinase production of Bacillus sp. R2 ,two cell immobilization strategies were conducted. The physical adsorption on different carriers showed that the highest chitinase activity was obtained by the carrier luffa pulp followed by flaked crab shell chitin with enhancement of 1.42 and 1.27 fold respectively. The entrapment immobilization in different gel matrices indicated that cell entrapment in 2% agar and 2% calcium alginate gave the highest chitinase activity 44 U/ml and 42.51 U/ml, respectively. The successive reuse of immobilized cells was investigated for 7 cycles over a period of one month. The results revealed that agar beads retained 100% or more of its original chitinase activity after 4 cycles and 86.5%, 75.5% and 60.9% of activity after the 5 th , 6 th and 7 th cycle respectively. On the other hand the alginate beads 2% and 4% retained more than 65% and 79.5% of their initial activity after 4 cycles. The effect of storage stability of beads on cell viability and chitinase production also was examined. The result showed that the longer shelf life was attained with agar beads which retain 50% of its initial activity after one month. From these optimizations, we recommend the physical adsorption immobilization on luffa pulp carrier for chitinase continuous production. Introduction hitin, a β-(1-4) homopolymer of N-acetyl -D-glucosamine (Glc NAc), is the second most abundant polysaccharide existing in nature after cellulose. It is a major structural component of most biological systems such as mollusks, insects, crustaceans, fungi, algae and marine invertebrates [1] . Chitin and its derivatives are of commercial and biotechnological interest because they have various biological activities and wide range of applications in areas ranging from waste water treatment to agrochemical and biomedical uses[2,3,4,5]. Chitinases (E.C. are found in variety of organisms such as viruses, bacteria, actinomycetes, yeasts, fungi, plants, animals and also in human beings [6, 7]. During the last decade, chitinases have received an increased attention due to their wider ranges of biotechnological applications especially in the biocontrol of fungal phytopathogens [8] and harmful insects [9]. They have also been used as vaccine [10], antitumor [11], tumor marker [12] and useful biomarker in Gaucher disease [13] and used in the preparation of sphaeroplasts and protoplasts from yeasts and fungal species which can be used further for biotechnological uses [14]. The application of immobilized whole cells for the production of metabolites by microorganisms has been extensively studied and several products of value such as alcohols[15],organic acids, amino acids, antibiotics, steroids, and enzymes[16,17,18] has been successfully obtained. Whole cells immobilization for extracellular enzymes production offers many advantages, such as increase of productivity due to high cell concentration, reduction of washout of microorganisms in continuous operation, easy cell separation from the culture broth for repeated use, and improvement in mass and heat transfer [19]. In the previous studies, Bacillus sp.R2 was screened as hyper chitinase producer and identified, furthermore, its chitinase production was optimized. In the present work we reported the improvement of chitinase production through two cell immobilization strategies, the physical adsorption on different carriers and entrapment in various gel matrices.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This paper introduces an efficient technique for designing a parameterized family of one- and multi-dimensional filters by regarding it as a single multi-dimensional filter. The new design technique is very fast since it reduces the design of a large set of filters to the design of a complex or real one-dimensional filter which is then mapped to produce the desired set of filters. It has the additional advantage that the one- and multi-dimensional filters in the set can be designed and realized efficiently without having to explicitly compute the coefficients of the separate filters. Among the types of filters which can be designed with this technique are seismic migration filters and linear-phase filters
    Acoustics, Speech, and Signal Processing, 1996. ICASSP-96. Conference Proceedings., 1996 IEEE International Conference on; 06/1996
Show more

Similar Publications