title: Establishment of using serum YKL-40 and SCCA in combination for the diagnosis of patients with esophageal squamous cell carcinoma.
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.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.forename: Shan
authors.initials: S
authors.lastname: Xing
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Pei-Dong
authors.initials: PD
authors.lastname: Chi
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Shu-Qin
authors.initials: SQ
authors.lastname: Dai
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Oncology in Southern China, Guangzhou, China. zengmsh@sysucc.org.cn.
authors.forename: Mu-Sheng
authors.initials: MS
authors.lastname: Zeng
authors.forename: Wan-Li
authors.initials: WL
authors.lastname: Liu
mesh_terms: D054392:Adipokines / Q000097:blood* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis*; D045744:Cell Line, Tumor; D000071451:Chitinase-3-Like Protein 1; D004938:Esophageal Neoplasms / Q000097:blood / Q000175:diagnosis*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D037102:Lectins / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015843:Serpins / Q000097:blood* / Q000235:genetics
chemical_list: D054392:Adipokines; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D015843:Serpins; C051072:squamous cell carcinoma-related antigen