Establishment of using serum YKL-40 and SCCA in combination for the diagnosis of patients with esophageal squamous cell carcinoma

BMC Cancer. 2014 Jul 7:14:490. doi: 10.1186/1471-2407-14-490.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood*
  • Adipokines / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / blood*
  • Antigens, Neoplasm / genetics
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / diagnosis*
  • Cell Line, Tumor
  • Chitinase-3-Like Protein 1
  • Esophageal Neoplasms / blood
  • Esophageal Neoplasms / diagnosis*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lectins / blood*
  • Lectins / genetics
  • Male
  • Middle Aged
  • Serpins / blood*
  • Serpins / genetics

Substances

  • Adipokines
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Lectins
  • Serpins
  • squamous cell carcinoma-related antigen