Abstract
BackgroundElevated 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).MethodsYKL-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.ResultsYKL-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).ConclusionsESCC 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.
Highlights
Elevated serum Chitinase-3-like-1 protein (YKL-40) levels have been observed in various cancers
Expression of YKL-40 in esophageal carcinoma cell lines and tumor tissues To investigate the expression of YKL-40 in esophageal squamous cell carcinoma (ESCC), the YKL-40 mRNA and protein levels were detected by real-time RT-PCR and Western Blotting, respectively, in several esophageal carcinoma cell lines (Eca-109, Kyse180, Kyse510, Kyse30, Kyse140 and Kyse520) and the immortalized esophageal epithelial cell line NE-3
Consistent with the results of the mRNA analysis, YKL-40 protein expression was up-regulated in the ESCC cell lines
Summary
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). Esophageal squamous cell carcinoma (ESCC) is typically diagnosed at a late state and has a very high mortality rate It is the sixth leading cause of cancer mortalities worldwide [1]. Our previous study reported that CEA and CYFRA21-1 exhibited sensitivities of 13.4% and 32.1% for the detection of ESCC, respectively [9]. These results indicate that the sensitivity of the traditional ESCC tumor markers is too low to diagnose esophageal cancer diagnosis. There is an urgent need to identify tumor markers to improve the sensitivity of ESCC detection
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