Abstract
Prognostic and predictive markers are needed to predict the clinical outcomes of patients with advanced colorectal cancer (CRC) who receive standard first-line treatments. We performed a prospective cohort study in advanced CRC patients to identify a miRNA signature that could predict the benefit of receiving first-line chemotherapy for these patients. Twenty-one paired tumours and adjacent normal tissues were collected from advanced CRC patients and analysed by miRNA microarrays. Between tumour and normal tissues, 33 miRNAs were differentially expressed and was confirmed by qRT-PCR from another group of 67 patients from a prospective cohort study. A two-miRNA-based signature was obtained using the LASSO Cox regression model based on the association between the expression of each miRNA and the PFS of individual patients. Internal and external validation cohorts, including 40 and 44 patients with advanced CRC, respectively, were performed to prove the prognostic and predictive value of this signature. A signature was built based on two miRNAs, miR-125b-2-3p and miR-933. CRC patients were classified into low- and high-risk groups for disease progression based on this tool. The patients with low risk scores generally had better PFS than those with high risk scores. In the training set, the median PFS in the low- and high-risk groups were 12.00 and 7.40 months, respectively. In the internal validation set, the median PFS in the low- and high-risk groups were 9.90 and 5.10 months, respectively. In the external validation set, the median PFS in the low- and high-risk groups were 9.90 and 6.40 months, respectively. Furthermore, we detected miR-125b-2-3p associated with CRC cell sensitivity to first-line chemotherapy. Our two-miRNA-based signature was a reliable prognostic and predictive tool for tumour progression in patients with advanced CRC, and might be able to predict the benefit of receiving standard first-line chemotherapy in CRC.
Highlights
Colorectal cancer (CRC) is the third most common cancer diagnosed in both men and women and is the fourth leading cause of cancer-related death worldwide[1,2]
Identifying effective biomarkers is essential for improving the prediction of treatment responses and guiding treatment decisions in advanced CRC patients
Twenty-one pairs of tumour and adjacent normal tissues from advanced CRC patients were used in the microarray analysis
Summary
Colorectal cancer (CRC) is the third most common cancer diagnosed in both men and women and is the fourth leading cause of cancer-related death worldwide[1,2]. Identifying effective biomarkers is essential for improving the prediction of treatment responses and guiding treatment decisions in advanced CRC patients. MiRNAs are involved in varied biological and pathophysiological processes, such as the cell cycle, cell differentiation, proliferation, apoptosis, etc.[12,13,14]. Apart from their important roles in biological processes, miRNAs participate in a wide range of diseases, including many types of cancers[15,16]. MiRNAs are studied as candidates for diagnostic and prognostic biomarkers and predictors of drug responses[17,18]. Compared to a single biomarker, integrating multiple biomarkers into a single model can significantly improve the predictive value[22,23]
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