Background With the increasing incidence of colorectal cancer (CRC), its accurate diagnosis is critical and in high demand. However, conventional methods are not ideal due to invasiveness and low accuracy. Herein, we aimed to identify efficient CRC mRNA markers in a non-invasive manner using CRC-derived extracellular vesicles (EVs). The expression levels of EV mRNAs from cancer cell lines were compared with those of a normal cell line using quantitative polymerase chain reaction. Eight markers were evaluated in plasma EVs from CRC patients and healthy controls. The diagnostic value of each marker, individually or in combination, was then determined using recessive operating characteristics analyses and the Mann-Whitney U test. Results Eight mRNA markers (MYC, VEGF, CDX2, CD133, CEA, CK19, EpCAM, and CD24) were found to be more abundant in EVs derived from cancer cell lines compared to control cell lines. A combination of VEGF and CD133 showed the highest sensitivity (100%), specificity (80%), and accuracy (93%) and an area under the curve of 0.96; hence, these markers were deemed to be the CRC signature. Moreover, this signature was found to be highly expressed in CRC-derived EVs compared to healthy controls. Conclusions VEGF and CD133 mRNAs comprise a unique CRC signature in EVs that has the potential to act as a novel, non-invasive, and accurate biomarker that would improve the current diagnostic platform for CRC, while also serving to strengthen the value of EV mRNA as diagnostic markers for myriad of diseases.

中文翻译：

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细胞外囊泡中的特征 mRNA 标记物可用于准确诊断结直肠癌。

背景随着结直肠癌（CRC）发病率的增加，其准确诊断至关重要且需求量很大。然而，由于侵入性和准确性低，传统方法并不理想。在此，我们的目的是使用 CRC 衍生的细胞外囊泡 (EV) 以非侵入性方式鉴定有效的 CRC mRNA 标记物。使用定量聚合酶链反应将癌细胞系的 EV mRNA 的表达水平与正常细胞系的表达水平进行比较。在 CRC 患者和健康对照的血浆 EV 中评估了八种标记物。然后使用隐性操作特征分析和曼-惠特尼 U 检验确定每个标志物单独或组合的诊断价值。结果发现与对照细胞系相比，源自癌细胞系的 EV 中的八种 mRNA 标记物（MYC、VEGF、CDX2、CD133、CEA、CK19、EpCAM 和 CD24）更加丰富。VEGF 和 CD133 的组合显示出最高的敏感性 (100%)、特异性 (80%) 和准确性 (93%)，曲线下面积为 0.96；因此，这些标记被认为是 CRC 签名。此外，与健康对照相比，该特征在 CRC 衍生的 EV 中高度表达。结论 VEGF 和 CD133 mRNA 在 EV 中包含独特的 CRC 特征，有可能作为一种新型、非侵入性且准确的生物标志物，改善当前的 CRC 诊断平台，同时也有助于增强 EV mRNA 作为诊断工具的价值。多种疾病的诊断标记。