A Liquid Biopsy Signature for the Detection of Patients With Early-Onset Colorectal Cancer

Gastroenterology. 2022 Nov;163(5):1242-1251.e2. doi: 10.1053/j.gastro.2022.06.089. Epub 2022 Jul 16.


Background & aims: Early-onset colorectal cancer (EOCRC) is a distinct clinical and molecular entity with poor survival outcomes compared with late-onset CRC. Although the incidence of EOCRC is rising, current CRC screening strategies have several limitations in diagnostic performance for EOCRC. In view of this clinical challenge, novel and robust biomarkers for detection of EOCRC are necessary. The aim of this study was to develop a circulating micro RNA (miRNA) signature for the diagnosis of patients with EOCRC.

Methods: A systematic discovery approach by analyzing a large, publicly available, noncoding RNA expression profiling dataset (GSE115513) was used. A panel of miRNAs was identified, which was subsequently validated in blood samples from patients with EOCRC in 2 independent cohorts (n = 149) compared with controls (n = 110) and pre/postoperative plasma specimens (n = 22) using quantitative reverse-transcription polymerase chain reaction assays.

Results: In the discovery phase, 4 miRNAs were found to be expressed in blood samples. A combination signature of these 4 miRNAs (miR-193a-5p, miR-210, miR-513a-5p, and miR-628-3p) yielded an area under the curve of 0.92 (95% confidence interval, 0.85-0.96) for identification of EOCRC in the training cohort. The miRNA panel performance was then confirmed in an independent validation cohort (area under the curve, 0.88; 95% confidence interval, 0.82-0.93). Moreover, the miRNA panel robustly identified patients with early-stage EOCRC (P < .001). The decreased expression of miRNAs in postsurgery plasma specimens indicated their tumor specificity.

Conclusions: Our novel miRNA signature for the diagnosis of EOCRC has the potential to identify patients with EOCRC with high accuracy for clinical application in the noninvasive diagnosis of EOCRC.

Keywords: Diagnostic Biomarker; Early-Onset Colorectal Cancer; Liquid Biopsy; miRNA Panel.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers, Tumor / genetics
  • Circulating MicroRNA*
  • Colorectal Neoplasms* / diagnosis
  • Colorectal Neoplasms* / genetics
  • Gene Expression Profiling
  • Humans
  • Liquid Biopsy
  • MicroRNAs* / genetics
  • ROC Curve


  • Biomarkers, Tumor
  • Circulating MicroRNA
  • MicroRNAs
  • MIRN628 microRNA, human