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MicroRNAs predict and modulate responses to chemotherapy in colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is the fourth leading cause of cancer-related death globally. Chemotherapy regimens consisting of 5-fluorouracil (5-FU) in combination with either oxaliplatin or irinotecan are the first-line options for treatment of metastatic CRC. However, primary or acquired resistance to these chemotherapeutics is a major clinical challenge. MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression post-transcriptionally. miRNAs play important roles in many cancer-related processes, including cell proliferation, apoptosis and invasion, and their dysregulation is implicated in colorectal tumourigenesis. Pertinent to chemotherapy, increasing evidence has revealed that miRNAs can be directly linked to chemosensitivity in CRC. In this review, we summarize current evidence concerning the role of miRNAs in prediction and modulation of cellular responses to 5-FU, oxaliplatin and irinotecan in CRC. We also discuss the possible targets and intracellular pathways involved in these processes.

SUBMITTER: Yu X

PROVIDER: S-EPMC6496401 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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MicroRNAs predict and modulate responses to chemotherapy in colorectal cancer.

Yu Xin X Li Zheng Z Yu Jun J Chan Matthew T V MT Wu William K K WK

Cell proliferation 20150722 5

Colorectal cancer (CRC) is the fourth leading cause of cancer-related death globally. Chemotherapy regimens consisting of 5-fluorouracil (5-FU) in combination with either oxaliplatin or irinotecan are the first-line options for treatment of metastatic CRC. However, primary or acquired resistance to these chemotherapeutics is a major clinical challenge. MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression post-transcriptionally. miRNAs play important roles in many ...[more]

PMID: 26202377

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Project description:PurposemiRNAs have been linked to chemosensitivity of breast cancer cells in vitro. In patients, however, there is no clinically validated method for predicting chemotherapy response. The aim of this study was to assess whether (I) a specific pattern of miRNA expression in pretherapeutic biopsies can predict response to neoadjuvant chemotherapy, and (II) differential miRNA expression in residual tumor after completion of chemotherapy allows further prognostic stratification of non-responding patients.MethodsSixty-four patients with newly diagnosed large (≥3 cm) or locally advanced primary breast cancers who underwent neoadjuvant anthracycline/taxane-based chemotherapy were included. Relative expression of 10 miRNAs likely to be associated with chemotherapy response (miR-7,-21,-29a,-29b,-34a,-125b,-155,-200c,-340,-451) was determined by quantitative RT-PCR from pretherapeutic biopsies (n = 64) and residual invasive tumor after chemotherapy (n = 42). Pathologic complete response (pCR) defined by absence of invasive tumor served as reference standard. In addition, miRNA expression was compared with disease-free and overall survival.ResultsNine (14%) of 64 patients achieved pCR. High expression of miR-7 and low expression of miR-340 in pretherapeutic biopsies predicted pCR with a negative predictive value of 96 and 97%, respectively (specificity 54 and 57%). The combined profile of miR-7high/miR-340low demonstrated improved specificity of 86% while maintaining a high negative predictive value (96%) to identify non-responders. Pretherapeutic expression of miR-200c and miR-155 showed prognostic information, and low expression was associated with increased overall survival (115 vs. 90 months, p ≤ 0.03). After chemotherapy, the overall survival of patients with residual invasive tumor was better for those demonstrating low miR-7 or high miR-125b (p = 0.01).ConclusionsIntratumoral expression of miR-7 and miR-340 prior to neoadjuvant chemotherapy could be used to predict pCR and a profile of miR-7low or miR-340high identified patients unlikely to achieve pCR who might benefit from alternative treatment options including earlier surgery. Our study identifies miRNAs as promising predictive biomarkers, which could aid in optimization of breast cancer management and treatment stratification.

Dataset Information

MicroRNAs predict and modulate responses to chemotherapy in colorectal cancer.

Publications

MicroRNAs predict and modulate responses to chemotherapy in colorectal cancer.

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