Serum microRNA panel as biomarkers for early diagnosis of colorectal adenocarcinoma

Abstract

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.

A Highly Predictive Model for Diagnosis of Colorectal Neoplasms Using Plasma MicroRNA

“…Another sixteen miRNAs were significantly dysregulated when comparing colorectal neoplasia (CRC and CAA) (n=20) to other cancers (BC, PC, LC) (n=30) (Comparison 2) and a further six miRNAs were significantly dysregulated between colorectal cancer (n=10) and colorectal advanced adenoma (n=10) (Comparison 3) . After reviewing the significantly dysregulated miRNA based on the adjusted p -value, AUC, fold change and biological significance, 6,9,22–29 ten miRNAs and two endogenous reference miRNA were selected for further study [Table 2]. …”

“…6 Plasma or serum miRNA panels have been described as biomarkers for detection of hepatocellular, lung, pancreatic, gastric and colorectal cancers. 22,61–66 …”

Predictive microRNAs for lymph node metastasis in endoscopically resectable submucosal colorectal cancer

“…The ROC curves showed AUC values of 0.845, 0.806, 0.791, 0.784, 0.778 and 0.778 for miR-342-3p, miR-195-5p, miR-150-5p, miR3621, miR140-3p and miR-361-3p, respectively (Table 2). To increase the prediction efficiency, we performed multiple logistic regression analysis with backward selection method as described previously [17]. Through the logistic regression analysis, we selected the classifier comprised of the three miRNAs; Logit (P) = 7.37 - (9.95*miR-342-3p) + (4.241*miR-3621) - (8.135*miR361-3p) (Supplementary Table S4).…”

MicroRNAs as potential drug targets for therapeutic intervention in colorectal cancer

“…It has been reported that downregulation of miR-375 in plasma and tissue of CRC patients correlated well with disease progression and decreased survival chances [105]. Recently, Zheng et al [106] have identified a panel of four miRNAs (miR-19a-3p, miR-223 --3p, miR-92a-3p and miR-422a) by analyzing serum samples collected from 307 CAC patients, 164 CA patients and 226 healthy controls. The developed panel demonstrated high diagnostic accuracy for CAC and differentiated well-stage I/II CAC from controls.…”