The potential of plasma microRNAs as non-invasive biomarkers in patients with colorectal cancer in advanced tumor-node-metastasis stages.

Abstract

Objective: MicroRNAs (miRNAs) are non-coding RNAs that participate actively in the post-transcriptional regulation of tumor suppressors, oncogenes, and DNA repair genes implicated in colorectal cancer (CRC). MiRNAs have been promising biomarkers for disease detection in recent years. The present study aimed to explore 16 candidate miRNAs in plasma samples as potential biomarkers for the detection and evolution of CRC.

Materials and methods: This study recruited 40 plasma samples of CRC patients [tumor-node-metastasis (TNM) stage III and IV] and 20 healthy controls. The expression of 16 miRNAs was evaluated by a quantitative Reverse Transcription-Polymerase Chain Reaction. The diagnostic value of miRNAs was evaluated by receiver operating characteristic analysis.

Results: The principal findings were that hsa-miR-31-5p was up-regulated in CRC patients vs. control group (p = 0.008), and by clinical stage TNM III and TNM IV (p = 0.011 and p = 0.018, respectively). This miRNA shows good diagnostic potential in CRC patients (AUC: 0.750, CI: 0.61-0.88, PPV: 62.5%, NPV: 100%) and in the clinical stage TNM III (AUC: 0.800, CI: 0.62-0.97, PPV: 83.3%, NPV: 100%) and TNM IV (AUC: 0.700, CI: 0.49-0.90, PPV: 71.4%, NPV: 100%). The hsa-miR-23a-3p was up-regulated in CRC patients with TNM stage III (p = 0.016), showing good potential as a diagnostic biomarker in this stage (AUC: 0.750, CI: 0.56-0.93, PPV: 76.9%, NPV: 100%), and in combined analysis with the hsa-miR-31-5p (AUC: 0.775, CI: 0.64-0.90, PPV: 66.6%, NPV: 100%). The hsa-miR-30a-5p and hsa-miR-126-3p were down-regulated in TNM IV (p = 0.03 and p = 0.047). Hsa-miR-126-3p miRNA showed good potential as a diagnostic biomarker in TNM IV stage (AUC: 0.850 CI: 0.69-1.00, PPV: 83.3, NPV: 100%); furthermore, in a combined analysis utilizing carcinoembryonic antigen (CEA), the outcome was superior (AUC: 0.907, CI: 0.78-1.00, PPV: 90.9%, NPV: 100%).

Conclusions: The significance of hsa-miR-31-5p and hsa-miR-23a-3p as oncomirs was evident in CRC TNM III, whereas hsa-miR-126-3p and hsa-miR-30a-5p were relevant as tumor suppressors in CRC TNM IV. The hsa-miR-30a-5p, hsa-miR-126-3p, hsa-miR-31-5p, and hsa-miR-23a-3p are good diagnostic and prognostic biomarkers in CRC.