Novel urinary protein biomarker panel for early diagnosis of gastric cancer.

Novel urinary protein biomarker panel for early diagnosis of gastric cancer.
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DOI:
10.1038/s41416-020-01063-5
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发表时间:
2020-11
影响因子:
8.8
通讯作者:
Kataoka H
Kataoka H
中科院分区:
医学1区
文献类型:
--
作者:
Shimura T;Dayde D;Wang H;Okuda Y;Iwasaki H;Ebi M;Kitagawa M;Yamada T;Yamada T;Hanash SM;Taguchi A;Kataoka H

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为了发现胃癌早期诊断的非侵入性生物标志物,我们进行了一项病例对照研究,利用早期胃癌患者和健康对照组(HC)的尿液样本。在372例患者的尿液样本中,年龄和性别匹配的282例患者随机分为三组:18例患者为发现组;训练队列中有176名患者,验证队列中有88名患者。在综合定量蛋白质组学分析中鉴定的尿蛋白中,除幽门螺杆菌状态外,尿中TFF1 (uTFF1)和ADAM12 (uADAM12)水平是GC的独立诊断生物标志物。在训练组和验证组中,uTFF1、uADAM12和幽门螺杆菌组成的尿液生物标志物组在HC和GC患者之间有显著差异。在性别特异性生物标志物的分析中,该组合面板显示男性GC的AUC为0.858,而另一个uTFF1, uBARD1和H. pylori的组合面板也提供了良好的女性GC AUC为0.893。值得注意的是,每个小组甚至可以区分I期GC患者和HC患者(男性AUC = 0.850,女性AUC = 0.845)。新型尿蛋白生物标志物组代表了GC(包括早期疾病)有前途的非侵入性生物标志物。
With the goal of discovering non-invasive biomarkers for early diagnosis of GC, we conducted a case-control study utilising urine samples from individuals with predominantly early GC vs. healthy control (HC). Among urine samples from 372 patients, age- and sex-matched 282 patients were randomly divided into three groups: 18 patients in a discovery cohort; 176 patients in a training cohort and 88 patients in a validation cohort. Among urinary proteins identified in the comprehensive quantitative proteomics analysis, urinary levels of TFF1 (uTFF1) and ADAM12 (uADAM12) were significantly independent diagnostic biomarkers for GC, in addition to Helicobacter pylori status. A urinary biomarker panel combining uTFF1, uADAM12 and H. pylori significantly distinguished between HC and GC patients in both training and validation cohorts. On the analysis for sex-specific biomarkers, this combination panel demonstrated a good AUC of 0.858 for male GC, whereas another combination panel of uTFF1, uBARD1 and H. pylori also provided a good AUC of 0.893 for female GC. Notably, each panel could distinguish even stage I GC patients from HC patients (AUC = 0.850 for males; AUC = 0.845 for females). Novel urinary protein biomarker panels represent promising non-invasive biomarkers for GC, including early-stage disease.
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