Teaching and Research Section, Epidemiology and Health Statistics, Public Health and Management Institute, Chongqing Medical University, Chongqing 400010, China.
Cancer Epidemiol. 2012 Oct;36(5):e294-9. doi: 10.1016/j.canep.2012.05.012. Epub 2012 Jun 23.
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.
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.
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.
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.
中性粒细胞明胶酶相关脂质运载蛋白（NGAL）及其细胞表面受体 NGALR 已被牵连到各种人类恶性肿瘤的发生和肿瘤进展中。特别是，已经证明 NGAL 在肝细胞癌（HCC）组织中过表达，并与 HCC 细胞的增殖和侵袭密切相关。本研究旨在探讨 NGAL 和 NGALR 在 HCC 中的临床意义。
通过免疫组织化学法检测 138 例接受 HCC 根治性切除术患者肿瘤组织中 NGAL 和 NGALR 的表达。分析 NGAL 或 NGALR 表达与临床病理特征的关系。采用单因素和多因素分析评估 NGAL 和/或 NGALR 表达对 HCC 患者的预后价值。
NGAL 和 NGALR 的表达水平在 HCC 组织中均上调，并与血管侵犯（均 P=0.03）、TNM 分期（均 P=0.004）和肿瘤复发（均 P<0.001）相关。还观察到两种标志物表达之间存在正相关（r=0.89；P<0.001）。此外，生存分析表明，NGAL 或 NGALR 的高表达与 HCC 患者的预后不良显著相关（均 P=0.003）。同时高表达 NGAL 和 NGALR 的患者总生存时间明显短于两者均低表达的患者（P<0.001）。此外，多因素分析表明，NGAL 和 NGALR 均是总生存的独立预测因素。
我们的数据首次表明，HCC 中 NGAL 和 NGALR 表达的上调均与不良的临床病理特征显著相关，是总生存的独立预后不良因素。这些发现表明，NGAL 和 NGALR 的表达可能成为 HCC 的新型预后因素和潜在治疗靶点。
