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Differentially Expressed MiRNAs Associated with Circulating Tumor Cell Status in Metastatic Colorectal Cancer

ABSTRACT: Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. Recent studies suggest the promising potential of microRNAs (miRNA) in predicting the status of circulating tumor cells (CTC), and their combined analyses could pave the way for significant advancements in assessing the risk of metastatic cancer. Here, we investigate the circulating miRNA signatures associated with CTC status in metastatic CRC (mCRC). The CTC status was assessed using AdnaTest ColonCancer technology, which detects tumor cells using an immunomagnetic approach and characterizes them based on colon-specific surface markers. The miRNA profiles were then analyzed using the Agilent miRNA microarray platform in 8 CTC-positive, 8 CTC-negative, and eight healthy individuals. The functional implications of dysregulated miRNAs and their interactions with target mRNAs, TFs, and lncRNAs were determined through a comprehensive in silico analysis. We identified two groups of downregulated miRNAs associated with CTC status/metastasis and multiple candidate biomarkers in suggested miRNA regulatory networks. Four miRNAs (miR-181c-5p, miR-199a-5p, miR-500b-5p, miR-769-5p) were prioritized as findings were consistent with their tissue expressions in TCGA datasets. Our findings reveal candidate biomarkers with potential for CTC status and mCRC-associated CTC detection, providing insights for new translational medicine applications in mCRC management.

ORGANISM(S): Homo sapiens

PROVIDER: GSE285322 | GEO | 2025/04/16

REPOSITORIES: GEO

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Project description:Metastatic colorectal cancer (mCRC) relies on the detachment of aggressive malignant cells from the primary tumor into the bloodstream, these Circulating Tumor Cells (CTC) being the principal source of the further metastasis. Here, we approached the massive molecular profiling of the CTC population isolated from mCRC patients. Clinically, the presence of CTC is associated with poor prognosis and there exists a clear necessity for more specific and efficient chemotherapies in the treatment of mCRC. Immunoisolation of CTC from these patients combined with a whole transcriptome amplification and hybridization onto gene expression arrays, lead us to specifically describe for the first time a CTC population with adhesive and migratory characteristics, in addition to a modulated expression of genes related to cell death and survival. Furthermore, bioinformatic analysis provided with an armamentarium of highly specific and sensitive valuable markers that should impact on the management and follow-up of mCRC patients. Finally, molecular profiling of CTC resulted in the identification of new therapeutic targets, like TGF-Î²1 impairing, specifically targeting the CTC population which should improve the efficacy in the eradication and prevention of CRC metastasis. In conclusion, molecular profiling of CTC represents an innovative and promising approach in the clinical management of mCRC patients. Circulating Tumor Cells (CTC) were immunoisolated from six metastatic colorectal patients (mCRC). Moreover, blood from three healthy donors were obtained, immunoisolating non-specific cellularity background. RNA was extracted and globally amplified with a Whole Transcriptome Amplification system. Samples were hybridized onto agilent arrays and CTC specific genes were obtained. Gene networks were built with IPA software and a gene ontology analysis was performed. Eleven candidate genes were validated by real time PCR. Finally, TGFB1 was evaluated as a potential drugable target against CTC population.

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Differentially Expressed MiRNAs Associated with Circulating Tumor Cell Status in Metastatic Colorectal Cancer

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