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基于血清代谢组学鉴定胰腺癌的可行性。

Feasibility of identifying pancreatic cancer based on serum metabolomics.

机构信息

Department of Surgery, University of Calgary, Calgary, Alberta, Canada.

出版信息

Cancer Epidemiol Biomarkers Prev. 2011 Jan;20(1):140-7. doi: 10.1158/1055-9965.EPI-10-0712. Epub 2010 Nov 23.

DOI:10.1158/1055-9965.EPI-10-0712
PMID:21098649
Abstract

BACKGROUND

We postulated that the abundance of various metabolites in blood would facilitate the diagnosis of pancreatic and biliary lesions, which could potentially prevent unnecessary surgery.

METHODS

Serum samples from patients with benign hepatobiliary disease (n = 43) and from patients with pancreatic cancer (n = 56) were examined by ¹H NMR spectroscopy to quantify 58 unique metabolites. Data were analyzed by "targeted profiling" followed by supervised pattern recognition and orthogonal partial least-squares discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups.

RESULTS

The metabolomic profile of patients with pancreatic cancer was significantly different from that of patients with benign disease (AUROC, area under the ROC curve, = 0.8372). Overt diabetes mellitus (DM) was identified as a possible confounding factor in the pancreatic cancer group. Thus, diabetics were excluded from further analysis. In this more homogeneous pancreatic cancer group, compared with benign cases, serum concentrations of glutamate and glucose were most elevated on multivariate analysis. In benign cases, creatine and glutamine were most abundant. To examine the usefulness of this test, a comparison was made to age- and gender-matched controls with benign lesions that mimic cancer, controlling also for presence of jaundice and diabetes (n = 14 per group). The metabolic profile in patients with pancreatic cancer remained distinguishable from patients with benign pancreatic lesions (AUROC = 0.8308).

CONCLUSIONS

The serum metabolomic profile may be useful for distinguishing benign from malignant pancreatic lesions.

IMPACT

Further studies will be required to study the effects of jaundice and diabetes. A more comprehensive metabolomic profile will be evaluated using mass spectrometry.

摘要

背景

我们推测血液中各种代谢物的丰度将有助于诊断胰腺和胆道病变,从而可能避免不必要的手术。

方法

通过 ¹H NMR 光谱检查来自良性肝胆疾病患者(n=43)和胰腺癌患者(n=56)的血清样本,以定量 58 种独特的代谢物。通过“靶向分析”分析数据,然后对最显著的代谢物进行有监督的模式识别和正交偏最小二乘判别分析(O-PLS-DA),这使得可以比较组间的整个样本谱。

结果

胰腺癌患者的代谢组学特征与良性疾病患者明显不同(AUROC,ROC 曲线下面积,=0.8372)。显性糖尿病(DM)被确定为胰腺癌组中的一个可能混杂因素。因此,糖尿病患者被排除在进一步分析之外。在这个更同质的胰腺癌组中,与良性病例相比,谷氨酸和葡萄糖的血清浓度在多变量分析中升高最明显。在良性病例中,肌酸和谷氨酰胺最为丰富。为了检验该检测的实用性,将其与具有模拟癌症的良性病变的年龄和性别匹配的对照进行了比较,同时也控制了黄疸和糖尿病的存在(每组 14 例)。胰腺癌患者的代谢谱仍可与良性胰腺病变患者区分(AUROC=0.8308)。

结论

血清代谢组学特征可用于区分良性和恶性胰腺病变。

影响

需要进一步研究黄疸和糖尿病的影响。将使用质谱法评估更全面的代谢组学谱。

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