Background: Currently, none of the available colorectal adenocarcinoma (CAC) testing has been established as a well-accepted diagnosis tool, particularly for the early stage of CAC. The recent discovery of serum microRNA (miRNA) profile has provided a new auxiliary approach for tumour diagnosis. Our study is involved in the global analysis of serum miRNAs during the normal-colorectal adenoma (CA)-CAC sequence.
Methods: Serum samples were collected from 307 CAC patients, 164 CA patients and 226 healthy controls. Differentially expressed serum miRNAs were screened with Miseq sequencing followed by the reverse transcription PCR (RT-qPCR) validation. The miRNA panel was developed with a logistic regression model and validated using an independent cohort. The miRNA levels in CAC patients of different clinical stages and CA patients of different grades were compared. Receiver operating characteristic curves were constructed to evaluate the diagnostic accuracy of the panel.
Results: The Miseq sequencing results revealed 15 differentially expressed miRNAs in the intersection of CAC vs CA and CA vs healthy controls according to our criteria. After the selection and validation process via RT-qPCR, we identified a four-miRNA panel (miR-19a-3p, miR-223-3p, miR-92a-3p and miR-422a) with a high diagnostic accuracy of CAC. Even in the low-carcinoembryonic antigen level group, the diagnostic accuracy of this miRNA panel was still acceptable (AUC=0.810). Surprisingly, our results indicated that the miRNA panel could differentiate stage I/II CAC from controls. In addition, this panel could also differentiate CA from CAC (AUC=0.886) and healthy controls (AUC=0.765).
Conclusions: We established a serum four-miRNA panel with considerable clinical value in the early-stage diagnosis of CAC.