NGAL and NGALR overexpression in human hepatocellular carcinoma toward a molecular prognostic classification.
OBJECTIVE
Neutrophil gelatinase-associated lipocalin (NGAL) and its cell surface receptor, NGALR, have been implicated in tumorigenesis and tumor progression of various human malignant neoplasms. In particularly, it has been demonstrated that NGAL is overexpressed in hepatocellular carcinoma (HCC) tissues and closely associated with the proliferation and invasion of HCC cells. The aim of this study was to investigate the clinical significance of NGAL and NGALR in HCC.


METHODS
Expression of NGAL and NGALR was evaluated by immunohistochemistry in tumor tissues from 138 patients who underwent curative resection of HCC. The association of NGAL or NGALR expression with the clinicopathologic features was analyzed. Univariate and multivariate analyses were performed to evaluate the prognostic value of NGAL and/or NGALR expression for HCC patients.


RESULTS
The expression levels of NGAL and NGALR were both up-regulated in HCC tissues, and to be associated with vascular invasion (both P=0.03), TNM stage (both P=0.004), and tumor recurrence (both P<0.001). A positive correlation between expression of the two markers was also observed (r=0.89; P<0.001). Additionally, survival analysis showed that high expression of NGAL or NGALR was significantly associated with poor prognosis for patients with HCC (both P=0.003). Patients with high expression of both NGAL and NGALR had a shorter overall survival (P<0.001) than those with low expression of both. Furthermore, multivariate analysis showed both NGAL and NGALR were independent predictors of overall survival.


CONCLUSIONS
Our data demonstrate for the first time that the up-regulations of NGAL and NGALR expression in HCC were both significantly correlated with unfavorable clinicopathologic features and independent poor prognostic factor for overall survival in patients. These findings suggest that NGAL and NGALR expression might be served as novel prognostic factors and potential therapeutic targets in HCC.
Teaching and Research Section, Epidemiology and Health Statistics, Public Health and Management Institute, Chongqing Medical University, Chongqing 400010, China. zhangycmu@163.com
Yan
Y
Zhang
Yudong
Y
Fan
Zhechuan
Z
Mei
D000209:Acute-Phase Proteins / Q000032:analysis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000556:secondary; D002454:Cell Differentiation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D000071068:Lipocalin-2; D054834:Lipocalins / Q000032:analysis*; D008113:Liver Neoplasms / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D027701:Organic Cation Transport Proteins / Q000032:analysis*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D016019:Survival Analysis
D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D027701:Organic Cation Transport Proteins; D011518:Proto-Oncogene Proteins; C518841:SLC22A17 protein, human