Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers
Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers
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DOI：
10.1158/1078-0432.ccr-03-0165
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发表时间：
2004-04-01
影响因子：
11.5
通讯作者：
Goggins, M
中科院分区：
文献类型：
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作者：
Koopmann, J;Buckhaults, P;Goggins, M
目的：胰腺导管腺癌患者通常表现为疾病晚期，预后不佳。一个可能改善胰腺癌发病率和死亡率的有效策略是识别准确的非侵入性诊断标记物，使有症状的患者能够更早地诊断，并在无症状的胰腺癌高危人群中更早发现癌症。在本研究中，我们评估了血清巨噬细胞抑制细胞因子-1(MIC-1)作为胰腺癌标志物的作用。实验设计：利用国家生物技术信息中心基因表达数据库系列分析、寡核苷酸芯片分析、原位杂交和免疫组织化学方法检测MIC-1在胰腺癌、导管内乳头状黏液性肿瘤和胰腺癌细胞系中的表达。用双抗体夹心法测定80例胰腺癌、30例壶腹癌和胆管细胞癌、42例胰腺良性肿瘤、76例慢性胰腺炎和97例健康人血清MIC-1水平。结果：寡核苷酸芯片和基因表达序列分析显示，MIC-1RNA在胰腺癌、导管内乳头状黏液性肿瘤和胰腺癌细胞系中的表达水平均高于非肿瘤性胰腺导管上皮。原位杂交显示MIC-1在胰腺癌的恶性上皮细胞中有表达。免疫组织化学显示MIC-1蛋白在16例胰腺癌中有14例表达(88%)，在部分胰腺炎组中也有表达，在正常胰腺组织中无表达。胰腺导管腺癌(平均+/-SD，2428+/-2324pg/ml)、壶腹癌和胆管细胞癌(2123+/-2387pg/ml)患者血清MIC-1水平显著高于胰腺良性肿瘤(940+/-469pg/ml)、慢性胰腺炎(1364+/-1236pg/ml)和健康对照组(546+/-262pg/ml)。血清MIC-1和CA19-9(受试者工作特征曲线下面积分别为0.81和0.77)均升高(P<；0.05；受试者工作特征曲线下面积0.87；敏感性70%；特异性85%)。结论：血清MIC-1测定有助于胰腺癌的诊断。
Purpose: Patients with pancreatic ductal adenocarcinoma usually present with advanced-stage disease and a dismal prognosis. One effective strategy likely to improve the morbidity and mortality from pancreatic cancer would be the identification of accurate, noninvasive diagnostic markers that would enable earlier diagnosis of symptomatic patients and earlier detection of cancer in asymptomatic individuals at high risk for developing pancreatic cancer. In this study, we evaluated serum macrophage inhibitory cytokine-1 (MIC-1) as a marker of pancreatic cancer.Experimental Design: MIC-1 expression in primary pancreatic cancers, intraductal papillary mucinous neoplasms, and pancreatic cancer cell lines was determined using the National Center for Biotechnology Information serial analysis of gene expression database, oligonucleotide microarrays analysis, in situ hybridization, and immunohistochemistry. Serum MIC-1 levels were determined by ELISA in 80 patients with pancreatic adenocarcinomas, in 30 patients with ampullary and cholangiocellular carcinomas, in 42 patients with benign pancreatic tumors, in 76 patients with chronic pancreatitis, and in 97 healthy control subjects. The diagnostic performance of serum MIC-1 as a marker of pancreatic cancer was compared with that of serum CA19-9.Results: Oligonucleotide microarray and serial analysis of gene expression data demonstrated that MIC-1 RNA levels were higher in primary pancreatic cancers, intraductal papillary mucinous neoplasms, and pancreatic cancer cell lines than in nonneoplastic pancreatic ductal epithelium. MIC-1 expression was localized to the malignant epithelium in pancreatic adenocarcinomas by in situ hybridization. MIC-1 protein was expressed in 14 of 16 primary pancreatic adenocarcinomas (88%) by inummohistochemistry and was also expressed in some pancreata affected by pancreatitis but not in normal pancreas. Serum MIC-1 levels were significantly higher in patients with pancreatic ductal adenocarcinoma (mean +/- SD, 2428 +/- 2324 pg/ml) and in patients with ampullary and cholangiocellular carcinomas (2123 +/- 2387 pg/ml) than in those with benign pancreatic neoplasms (940 +/- 469 pg/ml), chronic pancreatitis (1364 +/- 1236 pg/ml), or in healthy controls (546 +/- 262 pg/ml). An elevated serum MIC-1 (defined as 2 SD above the mean for healthy controls) performed as well as CA19-9 (area under the receiver operating characteristic curve, 0.81 and 0.77, respectively), and the combination of MIC-1 and CA19-9 significantly improved diagnostic accuracy (P < 0.05; area under the receiver operating characteristic curve, 0.87; sensitivity, 70%; specificity, 85%).Conclusion: Serum MIC-1 measurement can aid in the diagnosis of pancreatic adenocarcinoma.