Serum Exosomal Dicer Is a Useful Biomarker for Early Detection of Differentiated Gastric Adenocarcinoma
Serum Exosomal Dicer Is a Useful Biomarker for Early Detection of Differentiated Gastric Adenocarcinoma
复制标题
血清外泌体 Dicer 是早期检测分化型胃腺癌的有用生物标志物
DOI：
10.1159/000510993
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Kataoka H.
中科院分区：
文献类型：
--
作者：
Okuda Y;Shimura T;Iwasaki H;Katano T;Kitagawa M;Nishigaki R;Fukusada S;Natsume M;Tanaka M;Nishie H;Ozeki K;Yamada T;Kataoka H.
背景与目的最近的基础研究发现，DICER存在于来源于癌细胞的外切体中，在microRNA的成熟和肿瘤的发生发展中起着至关重要的作用。基于这一新的基本概念，我们分析了血清胞外DICER作为胃肠道肿瘤诊断生物标志物的有效性。方法将691名登记的参与者分为3组：胃癌(GC)队列，183例(90例健康对照，93例GC)；食道癌(EC)队列，115例(90例HCS，25例EC)；以及结直肠癌(CRC)队列，188例(92例HCS，96例结直肠癌患者)。用电子显微镜、粒度分析仪和外切体标记物CD63验证分离的血清外切体的质量。结果GC组血清外切体DICER显著高于HC组(p=0.004)，而EC和CRC两组间差异无统计学意义。仅在分化型胃腺癌和未分化型胃腺癌中，血清Exosomal Disher显著升高。此外，无论幽门螺杆菌(H.Pylori)状态如何，血清Exosomal DICER均无显著差异。结合血清外体DICER和幽门螺杆菌状态的生物标志物组合区分HC和分化型GC患者，曲线下面积(AUC)为0.762。在早期诊断方面，这种组合区分了HC和I期分化型胃癌，AUC=0.758。结论血清Exosomal Dird是一种潜在的早期发现分化型胃腺癌的无创性诊断生物标志物。
Background and AimA recent basic study identified that Dicer is contained in exosomes derived from cancer cells and plays crucial roles in microRNA maturation and cancer development. Based on this novel basic concept, we analyzed the usefulness of serum exosomal Dicer as a diagnostic biomarker for gastrointestinal cancers.MethodsEnrolled participants (691) were categorized into 3 groups: gastric cancer (GC) cohort, 183 patients (90 healthy controls (HCs) and 93 GC patients); esophageal cancer (EC) cohort, 115 patients (90 HCs and 25 EC patients); and colorectal cancer (CRC) cohort, 188 patients (92 HCs and 96 CRC patients) after age-and sex matching using the propensity score. The quality of isolated serum exosomes was validated with an electron microscope, particle size analyzer, and exosome marker, CD63.ResultsSerum exosomal Dicer was significantly higher in the GC group than in the HC group (p= 0.004), whereas no significant differences were found in both EC and CRC cohorts. Serum exosomal Dicer was significantly higher in only differentiated gastric adenocarcinoma and not in the undifferentiated type. Moreover, serum exosomal Dicer showed no significant differences regardless of Helicobacter pylori (H. pylori) status. The biomarker panel combining serum exosomal Dicer with H. pylori status distinguished between HC and differentiated GC patients with an area under the curve (AUC) of 0.762. As for early-stage diagnosis, this combination distinguished between HC and stage I differentiated GC with an AUC= 0.758.ConclusionsSerum exosomal Dicer is a potential noninvasive diagnostic biomarker for early detection of differentiated gastric adenocarcinoma.