Abstract
BackgroundWith 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.ResultsEight 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.ConclusionsVEGF 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.
Highlights
With the increasing incidence of colorectal cancer (CRC), its accurate diagnosis is critical and in high demand
Based on the heatmap analysis of the 12 extracellular vesicles (EVs) candidate markers, eight messenger RNAs (mRNAs) (MYC, vascular endothelial growth factor (VEGF), caudal type homeobox-2 (CDX2), CD133, carcinoembryonic antigen (CEA), CK19, epithelial cell adhesion molecule (EpCAM), and CD24) were determined to be more highly expressed in CRC cell lines compared to the normal cell line and were, chosen for further analysis
Through a series of comparisons between all possible mRNA combinations, we found that the combining two specific mRNA markers (VEGF and CD133) achieved an area under the curve (AUC) of 0.96 with 100% sensitivity, 80% specificity and 93% accuracy; this was designated as the CRC signature (Fig. 3 and Table 3)
Summary
With the increasing incidence of colorectal cancer (CRC), its accurate diagnosis is critical and in high demand. A significantly increased survival rate has been observed in patients with stage I-III compared with. Colonoscopic screening and fecal occult blood test (FOBT) have been utilized to diagnose CRC patients in clinical settings [4, 5]. These techniques pose serious challenges for accurate diagnosis and effective cancer treatment. The FOBT is noninvasive, it exhibits poor sensitivity with high false positive rates [6,7,8]. The sensitivity and specificity for CEA detection are fairly poor, making it
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