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Advancing Colorectal Cancer Metastasis Detection: A Novel miRNA-based Approach
This research highlights the potential of circulating microRNAs (miRNAs) as non-invasive biomarkers for predicting circulating tumor cell (CTC) status in metastatic colorectal cancer (mCRC). The identified miRNAs offer a promising avenue for early metastasis detection and can support novel translational applications in colorectal cancer (CRC) management. Ultimately, this approach could reduce the reliance on invasive tissue biopsies and provide real-time insights into disease progression and therapeutic response.
However, it is crucial to acknowledge the limitations of this study. Firstly, only a portion of the differentially transcribed miRNAs underwent qPCR validation, necessitating further experimental confirmation for the remaining candidates. Secondly, the CTC detection platform employed (AdnaTest) targets a specific set of epithelial markers (CEA, EGFR, and EpCAM). Exploring CTC heterogeneity would benefit from more extensive detection platforms. Thirdly, the exclusion of non-metastatic CRC (nmCRC) patients prevents an assessment of the diagnostic utility of these miRNAs across the entire disease spectrum. Fourthly,the absence of some identified miRNAs in public datasets like TCGA limited the scope of external validation. Lastly, while target genes such as GPD2 and RPS6KA3 were predicted to have functional roles, their precise regulatory mechanisms and downstream effects require experimental elucidation. Therefore, further in vitro and in vivo studies are essential to confirm their regulatory roles and clinical significance. To translate these findings into clinical practice, large-scale, multicenter studies are imperative to validate the diagnostic and prognostic potential of these miRNAs across diverse patient populations and sample types.
Towards Clinical Validation of miRNA-Based Metastasis Tools
The three identified miRNAs represent promising liquid biopsy biomarkers for the non-invasive prediction of CTC status in mCRC. Clinically, they could complement or, in certain scenarios, replace existing CTC detection methods. Functionally, they provide valuable insights into the molecular mechanisms driving metastatic spread. Our future research directions include:
- Validation: Confirming the performance of these markers in larger, self-reliant patient cohorts.
- Integration: Developing comprehensive diagnostic panels that combine miRNA markers with established CTC assays.
- Therapeutic exploration: Investigating therapeutic strategies that target these miRNA networks to inhibit CRC metastasis.
our findings reveal a compelling set of circulating miRNAs associated with CTC status in mCRC. These molecules hold promise not only as diagnostic or prognostic indicators but also as functional mediators of metastasis. Upon further validation and clinical integration, these biomarkers could facilitate risk-based patient stratification and pave the way for the growth of novel miRNA-targeted therapies for CRC.Reference: Doğan B, pirim D, Işık Ö, Evrensel T. Candidate biomarkers associated with circulating tumor cell status in metastatic colorectal cancer. J Clin. Lab. Anal. 2025;39(7):e70013. doi:10.1002/jcla.70013
