Dataset Information

MiR-107 and miR-99a-3p predict chemotherapy response in patients with advanced colorectal cancer.

ABSTRACT: BACKGROUND: MicroRNAs (miRNAs) are involved in numerous biological and pathological processes including colorectal cancer (CRC). The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 78 patients with metastatic CRC (mCRC). METHODS: We examined expression levels of 667 miRNAs in the training cohort and evaluated their potential association with relevant clinical endpoints. We identified a miRNA profile that was analysed by RT-qPCR in an independent cohort. For a set of selected miRNAs, bioinformatic target predictions and pathway analysis were also performed. RESULTS: Eight miRNAs (let-7 g*, miR-107, miR-299-5p, miR-337-5p, miR-370, miR-505*, miR-889 and miR-99a-3p) were significant predictors of response to chemotherapy in the training cohort. In addition, overexpression of miR-107, miR-337-5p and miR-99a-3p, and underexpression of miR-889, were also significantly associated with improved progression-free and/or overall survival. MicroRNA-107 and miR-99a-3p were further validated in an independent cohort as predictive markers for chemotherapy response. In addition, an inverse correlation was confirmed in our study population between miR-107 levels and mRNA expression of several potential target genes (CCND1, DICER1, DROSHA and NFKB1). CONCLUSIONS: MiR-107 and miR-99a-3p were validated as predictors of response to standard fluoropyrimidine-based chemotherapy in patients with mCRC.

SUBMITTER: Molina-Pinelo S

PROVIDER: S-EPMC4167263 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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MiR-107 and miR-99a-3p predict chemotherapy response in patients with advanced colorectal cancer.

Molina-Pinelo Sonia S Carnero Amancio A Rivera Fernando F Estevez-Garcia Purificacion P Bozada Juan Manuel JM Limon Maria Luisa ML Benavent Marta M Gomez Javier J Pastor Maria Dolores MD Chaves Manuel M Suarez Rocio R Paz-Ares Luis L de la Portilla Fernando F Carranza-Carranza Andres A Sevilla Isabel I Vicioso Luis L Garcia-Carbonero Rocio R

BMC cancer 20140907

<h4>Background</h4>MicroRNAs (miRNAs) are involved in numerous biological and pathological processes including colorectal cancer (CRC). The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 78 patients with metastatic CRC (mCRC).<h4>Methods</h4>We examined expression levels of 667 miRNAs in the training cohort and evaluated their potential association with relevant clinical endpoints. We identified a miRNA profile that was a ...[more]

PMID: 25197016

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Project description:BACKGROUND; Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is around 50% and tumor derived molecular prognostic markers are needed for estimation of response and survival. METHODS; Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes having an expression with high correlation to survival time after chemotherapy was identified. Two of these genes were selected for validation by immunohistochemistry (IHC) in tumor tissue from 149 cisplatin treated patients having complete follow-up data. RESULTS; Fifty-five differentially expressed genes correlated significantly to survival time. Two of these (Emmprin and Survivin) were validated using IHC, and multivariate analysis (n=145) identified Emmprin expression (hazard ratio 2.38; p<0.0001) and Survivin expression (hazard ratio 2.34; p<0.0001) as independent prognostic markers for poor outcome, together with the presence of visceral metastases (hazard ratio 2.72; p<0.0001). In the good prognosis group of patients without visceral metastases, both markers showed significant discriminating power as supplemental risk factors (p<0.0001). Within this group of patients, the subgroups of patients with no positive, one positive or two positive IHC stainings (Emmprin and Survivin) had estimated 5-year survival rates (+- SE) of 35.6+-?%, 6.3+-?%, and 0+?%, respectively. Response to chemotherapy could also be predicted with an OddsRatio of 4.60 (2.13-9.93) and 2.59 (1.25-5.38) for Emmprin and Survivin respectively. CONCLUSION; Emmprin and Survivin proteins were identified as strong independent prognostic predictors for response and survival after cisplatin-containing chemotherapy in patients with bladder cancer. Experiment Overall Design: Tumors from 30 patients with advanced bladder cancer used in the study. A SAM analysis was used for identifying genes co-varying with treatment response.

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

MiR-107 and miR-99a-3p predict chemotherapy response in patients with advanced colorectal cancer.

Publications

MiR-107 and miR-99a-3p predict chemotherapy response in patients with advanced colorectal cancer.

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