ORIGINAL ARTICLE

Upregulation of neutrophil gelatinase-associated lipocalin in oesophageal squamous cell carcinoma: significant correlation with cell differentiation and tumour invasion

Haihua Zhang^1,*, Liyan Xu^2,*, Dawei Xiao³, Jianjun Xie¹, Hongmei Zeng¹, Zhaoyang Wang¹, Xiaoling Zhang¹, Yongdong Niu¹, Zhongying Shen², Jinghui Shen⁴, Xuan Wu⁴ and Enmin Li¹

¹ Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou,Guangdong Province, People’s Republic of China
² Department of Pathology, Medical College of Shantou University, Shantou, Guangdong Province, People’s Republic of China
³ Department of Cardiothoracic Surgery, The First Affiliated Hospital of Shantou University, Shantou, Guangdong Province, People’s Republic of China
⁴ Department of Clinical Pathology, Centre Hospital of Shantou City, Shantou, Guangdong Province, People’s Republic of China

Correspondence to:
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

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.

Abbreviations: 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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