Department of Oncology, The Second Affiliate Hospital of Harbin Medical University, Harbin, 150081, China.
Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
Sci Rep. 2017 Jun 23;7(1):4150. doi: 10.1038/s41598-017-04386-1.
Circulating exosome holds great potentials as biomarker for diagnosis and prognosis of human cancers. Previously, we have applied small RNA sequencing to identify aberrantly expressed exosomal miRNAs as candidates for diagnostic markers in colon cancer patients. In this validation cohort, plasma derived exosomal miRNA was isolated from 50 early-stage colon cancer patients and 50 matched healthy volunteers. Real-time qRT-PCR revealed that miR-125a-3p, miR-320c were significantly up-regulated in plasma exosomes of the patients with early stage colon cancer. ROC curve showed that miR-125a-3p abundant level may predict colon cancer with an area of under the curve (AUC) of 68.5%, in comparison to that of CEA at 83.6%. Combination of miR-125a-3P and CEA improved the AUC to 85.5%. In addition, plasma exosome level of miR-125a-3p and miR-320c showed significant correlation with nerve infiltration (P < 0.01), but not with tumor size, infiltration depth, and differentiation degree (P > 0.05). On the contrary, plasma CEA level is correlated with tumor size, infiltration depth, and differentiation degree (P < 0.05, r = 0.3009-0.7270), but not with nerve infiltration (P = 0.744). In conclusion, this follow-up study demonstrated circulating plasma exosomal miR-125a-3p is readily accessible as diagnosis biomarker for early-stage colon cancer. When combined with conventional diagnostic markers, miR-125a-3p can improve the diagnostic power.
循环外泌体作为人类癌症诊断和预后的生物标志物具有巨大的潜力。此前，我们应用小 RNA 测序来鉴定异常表达的外泌体 miRNA，将其作为结肠癌患者诊断标志物的候选者。在本验证队列中，从 50 例早期结肠癌患者和 50 例匹配的健康志愿者中分离出血浆来源的外泌体 miRNA。实时 qRT-PCR 显示，miR-125a-3p、miR-320c 在早期结肠癌患者血浆外泌体中显著上调。ROC 曲线显示，miR-125a-3p 丰度水平可预测结肠癌，曲线下面积（AUC）为 68.5%，而 CEA 为 83.6%。miR-125a-3P 和 CEA 的联合应用可将 AUC 提高至 85.5%。此外，miR-125a-3p 和 miR-320c 的血浆外泌体水平与神经浸润呈显著相关（P<0.01），但与肿瘤大小、浸润深度和分化程度无关（P>0.05）。相反，血浆 CEA 水平与肿瘤大小、浸润深度和分化程度相关（P<0.05，r=0.3009-0.7270），但与神经浸润无关（P=0.744）。总之，这项随访研究表明，循环血浆外泌体 miR-125a-3p 可作为早期结肠癌的诊断标志物。当与常规诊断标志物联合使用时，miR-125a-3p 可以提高诊断能力。
