Associations of blood RNA biomarkers and circulating tumour cells in patients with previously untreated metastatic colorectal cancer
Abstract Background In patients with metastatic colorectal cancer, analysis of the number of basal circulating tumour cells (bCTCs) has been shown to be a strong prognostic indicator. In this study, we aim to explore the potential associations between whole blood mRNA and microRNA expression profile...
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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-025-14098-9 |
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| Summary: | Abstract Background In patients with metastatic colorectal cancer, analysis of the number of basal circulating tumour cells (bCTCs) has been shown to be a strong prognostic indicator. In this study, we aim to explore the potential associations between whole blood mRNA and microRNA expression profiles and bCTC counts, tumour mutations and prognosis in untreated metastatic colorectal cancer patients. Methods A total of 151 patients previously screened for inclusion in two clinical trials (VISNÚ1 and VISNÚ2) were enrolled in this study. Real-time quantitative PCR (qPCR) analyses were performed to determine the whole blood expression of selected RNAs (mRNAs and microRNAs) involved in the metastatic process. The CellSearch system was used to enumerate circulating tumour cells. The primary objective was to correlate RNA expression with the number of bCTCs, while the secondary objectives were to investigate the relationship between the levels of circulating RNA biomarkers in whole blood and the clinical, pathological, and molecular characteristics and prognosis of patients with metastatic colorectal cancer. Results bCTC count was significantly associated with AGR2 mRNA in the entire cohort of 151 patients. AGR2, ADAR1 and LGR5 were associated with the number of bCTC, both in the subgroup with bCTC ≥ 3 and in the subgroup with native RAS/BRAF/PIK3 CA tumours. In patients with RAS/BRAF/PIK3 CA mutations no correlations with bCTC were detected, but an upregulation of miR-224-5p and the stemness marker LGR5 and a downregulation of immune regulatory CD274 were found. Lower levels of miR-106a-5p/miR-26a-5p were associated with shorter overall survival, with independent statistical significance in the multivariate analysis. Conclusions A correlation was identified between the levels of a subset of whole blood RNAs, including AGR2, ADAR1, and LGR5, and the number of bCTC and RAS/BRAF/PIK3 CA mutational status. Furthermore, another set of whole blood RNAs, specifically miR-106a-5p and miR-26a-5p, was found to be associated with poor prognosis. This may be helpful for risk stratification. Trial registration Clinical Trials Gov. NCT01640405 and NCT01640444. Registered on 13 June 2012. https://clinicaltrials.gov/ . |
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| ISSN: | 1471-2407 |