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Upregulation of neutrophil gelatinase-associated lipocalin in oesophageal squamous cell carcinoma: significant correlation with cell differentiation and tumour invasion
  1. Haihua Zhang1,*,
  2. Liyan Xu2,*,
  3. Dawei Xiao3,
  4. Jianjun Xie1,
  5. Hongmei Zeng1,
  6. Zhaoyang Wang1,
  7. Xiaoling Zhang1,
  8. Yongdong Niu1,
  9. Zhongying Shen2,
  10. Jinghui Shen4,
  11. Xuan Wu4,
  12. Enmin Li1
  1. 1Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou,Guangdong Province, People’s Republic of China
  2. 2Department of Pathology, Medical College of Shantou University, Shantou, Guangdong Province, People’s Republic of China
  3. 3Department of Cardiothoracic Surgery, The First Affiliated Hospital of Shantou University, Shantou, Guangdong Province, People’s Republic of China
  4. 4Department of Clinical Pathology, Centre Hospital of Shantou City, Shantou, Guangdong Province, People’s Republic of China
  1. Correspondence to:
 Dr E Li
 Department of Biochemistry and Molecular Biology, Medical College of Shantou University, 22 Xinling Road, Shantou 515041, Guangdong Province, People’s Republic of China; nmli{at}stu.edu.cn

Abstract

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family. Recently, an elevated NGAL expression was reported in several types of cancers. However, the characteristics of NGAL expression in oesophageal squamous cell carcinoma (ESCC) are still unknown.

Aim: To demonstrate the role of NGAL in ESCC.

Methods: NGAL expression in 81 paraffin sections, including ESCC, normal mucosa, simple hyperplasia and dysplasia, and in 73 fresh specimens of ESCC was analysed by immunohistochemistry, western blot and gelatin zymography.

Results: On immunohistochemical study, ESCC showed a diverse staining pattern for NGAL. However, only a weak positive signal was present within a restricted cytoplasmic area in the normal oesophageal epithelium. In dysplasia, altered NGAL expression could also be observed. On western blot study, NGAL expression level was found to be significantly higher in ESCC than in normal mucosa (p = 0.030), and to be positively correlated with cell differentiation. However, no significant association was observed between NGAL expression and cell proliferation. In addition, the enzymic activity of the NGAL/matrix metalloproteinase 9 complex was much higher in ESCC than in normal mucosa, and was significantly correlated with the depth of tumour invasion in zymography analysis (p = 0.006).

Conclusions: The findings suggest that NGAL is involved in the differentiation pathway and invasive progression of ESCC.

  • ESCC, oesophageal squamous cell carcinoma
  • MMP-9, matrix metalloproteinase 9
  • NGAL, neutrophil gelatinase-associated lipocalin
  • PBS, phosphate-buffered saline
  • PCNA, proliferating cell nuclear antigen

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Footnotes

  • * These authors contributed equally to this work.

  • Funding: This work was supported by grants from the National Natural Science Foundation of China (No. 39900069, No. 30170428, No. 30370641, No. 30570849); Specialised Research Fund for the Doctoral Program of Higher Education of China (No. 20050560002, No. 20050560003); Guangdong Scientific Fund Key Items (No. 37788, No. 05104541); and Natural Science Foundation of Guangdong Province (No. 010431).

  • Competing interests: None.

  • This study was approved by the ethical committee of the First Affiliated Hospital of Shantou University (Shantou City, Guangdong Province, People’s Republic of China), and written informed consent was obtained from all patients undergoing surgery to use resected samples for research.