Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia.
Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia.
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胰腺癌的早期诊断：中性粒细胞明胶酶相关的脂肪蛋白作为胰腺上皮内肿瘤的标志。
DOI：
10.1038/sj.bjc.6604329
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发表时间：
2008-05-06
影响因子：
8.8
通讯作者：
Batra SK
中科院分区：
文献类型：
--
作者：
Moniaux N;Chakraborty S;Yalniz M;Gonzalez J;Shostrom VK;Standop J;Lele SM;Ouellette M;Pour PM;Sasson AR;Brand RE;Hollingsworth MA;Jain M;Batra SK
胰腺癌是一种高致命性的恶性肿瘤，5年生存率低于5%。早期生物标志物的缺乏大大阻碍了我们及时采取预防措施的能力。据报道，在微阵列分析中，与正常导管细胞相比，胰腺癌细胞中的24-kDa糖蛋白--中性粒细胞明胶酶相关脂质运载蛋白（NGAL）上调近27倍。鉴于在胰腺癌的早期诊断中需要生物标志物，我们研究了NGAL在组织中的表达，目的是检查NGAL免疫染色是否可用于识别胰腺上皮内瘤变、浸润性癌前的癌前病变的病灶。为了研究NGAL表达与分化程度之间可能的相关性，我们还分析了具有不同分化程度的胰腺癌细胞系中的NGAL水平。虽然NGAL表达在胰腺癌中强烈上调，在胰腺炎中中度上调，但在健康胰腺中仅检测到弱表达。胰腺癌的平均综合评分（4.26±2.44）明显高于正常胰腺（1.0）和胰腺炎（1.0）（P<0.0001）。此外，尽管高分化和中等分化的胰腺癌NGAL阳性，但低分化腺癌均为阴性。重要的是，NGAL表达早在PanIN-1阶段就被检测到，这表明它可能是胰腺中最早的癌前病变的标志物。此外，我们检查了血清样品中的NGAL水平。在94%的胰腺癌和62.5%的急性和慢性胰腺炎样本中，血清NGAL水平高于健康个体的临界值。然而，胰腺炎和胰腺癌中NGAL水平之间的差异不显著。ROC曲线分析显示，NGAL的ELISA在区分胰腺癌与非癌病例中相当准确（曲线下面积=0.75）。总之，NGAL在胰腺早期发育不良病变中高度表达，提示其可能作为胰腺癌的早期诊断标志物。此外，血清NGAL测量可以作为胰腺炎和胰腺癌的可能生物标志物进行研究。
Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic intraepithelial neoplasia, premalignant lesions preceding invasive cancer. To examine a possible correlation between NGAL expression and the degree of differentiation, we also analysed NGAL levels in pancreatic cancer cell lines with varying grades of differentiation. Although NGAL expression was strongly upregulated in pancreatic cancer, and moderately in pancreatitis, only a weak expression could be detected in the healthy pancreas. The average composite score for adenocarcinoma (4.26±2.44) was significantly higher than that for the normal pancreas (1.0) or pancreatitis (1.0) (P<0.0001). Further, although both well- and moderately differentiated pancreatic cancer were positive for NGAL, poorly differentiated adenocarcinoma was uniformly negative. Importantly, NGAL expression was detected as early as the PanIN-1 stage, suggesting that it could be a marker of the earliest premalignant changes in the pancreas. Further, we examined NGAL levels in serum samples. Serum NGAL levels were above the cutoff for healthy individuals in 94% of pancreatic cancer and 62.5% each of acute and chronic pancreatitis samples. However, the difference between NGAL levels in pancreatitis and pancreatic cancer was not significant. A ROC curve analysis revealed that ELISA for NGAL is fairly accurate in distinguishing pancreatic cancer from non-cancer cases (area under curve=0.75). In conclusion, NGAL is highly expressed in early dysplastic lesions in the pancreas, suggesting a possible role as an early diagnostic marker for pancreatic cancer. Further, serum NGAL measurement could be investigated as a possible biomarker in pancreatitis and pancreatic adenocarcinoma.
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血浆中性粒细胞明胶酶相关的Lipocalin可预测小儿心脏手术后的急性肾脏损伤，发病率和死亡率：一项前瞻性不受控制的队列研究。
DOI：
10.1186/cc6192
发表时间：
2007
期刊：
Critical care (London, England)
影响因子：
--
作者：
Dent CL;Ma Q;Dastrala S;Bennett M;Mitsnefes MM;Barasch J;Devarajan P
通讯作者：
Devarajan P
影响因子：
16
作者：
Goetz, DH;Holmes, MA;Strong, RK
通讯作者：
Strong, RK
影响因子：
168.9
作者：
Mishra, J;Dent, C;Devarajan, P
通讯作者：
Devarajan, P
DOI：
10.1016/j.jamcollsurg.2004.01.008
发表时间：
2004-05-01
影响因子：
5.2
作者：
Cleary, SP;Gryfe, R;Gallinger, S
通讯作者：
Gallinger, S
影响因子：
4
作者：
Huang, HL;Chu, ST;Chen, YH
通讯作者：
Chen, YH