Itoi Takao, Sugimoto Masahiro, Umeda Junko, Sofuni Atsushi, Tsuchiya Takayoshi, Tsuji Shujiro, Tanaka Reina, Tonozuka Ryosuke, Honjo Mitsuyoshi, Moriyasu Fuminori, Kasuya Kazuhiko, Nagakawa Yuichi, Abe Yuta, Takano Kimihiro, Kawachi Shigeyuki, Shimazu Motohide, Soga Tomoyoshi, Tomita Masaru, Sunamura Makoto
Division of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan.
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
Int J Mol Sci. 2017 Apr 4;18(4):767. doi: 10.3390/ijms18040767.
This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC) from malignant diseases, such as biliary tract cancer (BTC), intraductal papillary mucinous carcinoma (IPMC), and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples ( = 41) of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples ( = 140). Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups ( < 0.05; Steel-Dwass test). Four multiple logistic regression models (MLR) were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC) of 0.970 (95% confidential interval (CI), 0.946-0.994, < 0.0001). Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650-1.01, = 0.0020) with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), pancreatic cancer-associated antigen (DUPAN2) and s-pancreas-1 antigen (SPAN1). Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.
本研究评估了血清代谢组学在鉴别恶性肿瘤(包括胰腺癌(PC))与恶性疾病(如胆管癌(BTC)、导管内乳头状黏液性癌(IPMC))以及各种良性胰胆疾病方面的临床应用。采用毛细管电泳 - 质谱法分析带电代谢物。我们对不同储存时长的血清样本(n = 41)进行了重复分析,以鉴定具有高定量重现性的代谢物,随后分析了所有样本(n = 140)。总体而言,共定量了189种代谢物,其中66种代谢物的变异系数为20%,在这些代谢物中,有24种在对照组、良性组和恶性组之间存在显著差异(P < 0.05;Steel - Dwass检验)。构建了四个多元逻辑回归模型(MLR),其中一个MLR模型能够清晰地将所有疾病患者与健康对照区分开来,受试者工作特征曲线下面积(AUC)为0.970(95%置信区间(CI),0.946 - 0.994,P < 0.0001)。另一个用于鉴别PC与BTC和IPMC的模型,其AUC = 0.831(95% CI,0.650 - 1.01,P = 0.0020),与包括癌胚抗原(CEA)、糖类抗原19 - 9(CA19 - 9)、胰腺癌相关抗原(DUPAN2)和s - 胰腺 - 1抗原(SPAN1)在内的肿瘤标志物相比,具有更高的准确性。代谢组学谱的变化可能用于筛查恶性肿瘤以及区分PC与其他恶性疾病。