NGAL expression is elevated in both colorectal adenoma-carcinoma sequence and cancer progression and enhances tumorigenesis in xenograft mouse models.
NGAL expression is elevated in both colorectal adenoma-carcinoma sequence and cancer progression and enhances tumorigenesis in xenograft mouse models.
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DOI：
10.1158/1078-0432.ccr-11-0226
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发表时间：
2011-07-01
期刊：
影响因子：
--
通讯作者：
Zhang W
中科院分区：
文献类型：
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作者：
Sun Y;Yokoi K;Li H;Gao J;Hu L;Liu B;Chen K;Hamilton SR;Fan D;Sun B;Zhang W
越来越多的证据表明，中性粒细胞明胶酶相关脂钙蛋白(NGAL)在癌症的发生发展中起着重要作用。然而，NGAL在结直肠癌中的作用尚不清楚。在这项研究中，我们研究了NGAL在结直肠癌发生发展中的作用，并评价了NGAL表达的临床价值。我们用免疫组织化学方法检测了526例大肠组织标本中NGAL的表达，其中包括53组匹配的标本(组织学正常粘膜、腺瘤和癌)。分析癌组织中NGAL表达与临床病理参数的相关性，并进行生存分析。在小鼠异种移植模型上进一步测试NGAL的作用。NGAL在结直肠腺瘤-癌序列中表达升高(rS=0.66，P<0.001)，在53例配对标本中表达升高(rS=0.6，P<0.001)。在大肠癌中，NGAL的表达与肿瘤分期有关(P=0.041)，与II期复发有关(P=0.037)。生存分析显示，NGAL的表达是影响总生存期(HR=1.84，P=0.004)和II期患者无病生存期(HR=5.88，P=0.021)的独立预后因素。在小鼠模型中，注射NGAL过表达的CRC细胞组盲肠和脾中的异种移植瘤更重、更多(P<；0.05)。NGAL过表达可能促进结直肠癌的发生和发展。检测肿瘤组织中NGAL的表达可能有助于判断结直肠癌患者的预后。
There is growing evidence implicating that neutrophil gelatinase–associated lipocalin (NGAL) plays a role in the development and progression of cancers. However, the effect of NGAL in colorectal carcinoma (CRC) has not been clearly elucidated. In this study, we investigated the role of NGAL in the tumorigenesis and progression of CRC and evaluated the clinical value of NGAL expression. We examined NGAL expression in 526 colorectal tissue samples, including 53 sets of matched specimens (histologically normal mucosa, adenomas, and carcinomas) using immunohistochemical analysis. In CRCs, correlations between NGAL expression and clinicopathologic parameters were analyzed, and survival analysis was conducted. The role of NGAL was further tested using mouse xenograft models. NGAL expression was elevated during the colorectal adenoma–carcinoma sequence both among the 526 cases (rs = 0.66, P < 0.001) and in the 53 sets of matched specimens (rs = 0.60, P < 0.001). In CRCs, NGAL expression was associated with cancer stage (P = 0.041) and tumor recurrence in stage II patients (P = 0.037). Survival analysis revealed that NGAL expression was an independent prognostic factor for overall survival (HR = 1.84, P = 0.004) and for disease-free survival of stage II patients (HR = 5.88, P = 0.021). In mouse models, the xenografts in cecum and spleen were heavier and more numerous in the group injected with NGAL-overexpressing CRC cells (P < 0.05). NGAL overexpression may promote the tumorigenesis and progression of CRC. Detecting NGAL expression in tumor tissues may be useful for evaluating prognosis of patients with CRC.