Combination of a six microRNA expression profile with four clinicopathological factors for response prediction of systemic treatment in patients with advanced colorectal cancer
Autor: | Tineke E. Buffart, Jan Hein T.M. van Waesberghe, Henk M.W. Verheul, Jan Dirk Burggraaf, Gerrit A. Meijer, Daoud Sie, Maarten Neerincx, Nicole C.T. van Grieken, Cornelis Verhoef, Bauke Ylstra, Ram C. Shankaraiah, Paul P. Eijk, Mark A. van de Wiel, Floor S.W. Van Der Wolf-De Lijster, Dennis Poel |
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Přispěvatelé: | Gastroenterology and hepatology, Medical oncology, AGEM - Re-generation and cancer of the digestive system, Human genetics, CCA - Imaging and biomarkers, Pathology, Radiology and nuclear medicine, Epidemiology and Data Science, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, NCA - Brain mechanisms in health and disease, Internal medicine, Surgery, Mathematics, Amsterdam Neuroscience - Complex Trait Genetics |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Oncology Molecular biology Colorectal cancer Cancer Treatment lcsh:Medicine Logistic regression Biochemistry Cohort Studies Sequencing techniques Mathematical and Statistical Techniques 0302 clinical medicine Medicine and Health Sciences DNA sequencing lcsh:Science Aged 80 and over Multidisciplinary Genomics MicroRNA Expression Profile Middle Aged Prognosis Tumor Resection Gene Expression Regulation Neoplastic Surgical Oncology Real-time polymerase chain reaction Area Under Curve 030220 oncology & carcinogenesis Physical Sciences Cohort Disease Progression Female Colorectal Neoplasms Transcriptome Analysis Statistics (Mathematics) Research Article Adult Next-Generation Sequencing Clinical Oncology medicine.medical_specialty Antineoplastic Agents Surgical and Invasive Medical Procedures 03 medical and health sciences SDG 3 - Good Health and Well-being Internal medicine Biomarkers Tumor Genetics medicine Adjuvant therapy Humans Clinical significance Statistical Methods Differentiated Tumors Aged Colorectal Cancer Surgical Resection business.industry lcsh:R Cancers and Neoplasms Biology and Life Sciences Computational Biology Genome Analysis medicine.disease Research and analysis methods MicroRNAs Molecular biology techniques 030104 developmental biology ROC Curve Metastatic Tumors lcsh:Q Clinical Medicine business Biomarkers Mathematics Progressive disease Forecasting |
Zdroj: | PLoS ONE, Vol 13, Iss 8, p e0201809 (2018) PLoS ONE, 13(8). Public Library of Science PLoS One (online), 13(8):e0201809. Public Library of Science PLoS ONE PLoS ONE, 13(8):e0201809, 1-20. Public Library of Science Neerincx, M, Poel, D, Sie, D L S, van Grieken, N C T, Shankaraiah, R C, Van Der Wolf-De Lijster, F S W, van Waesberghe, J H T M, Burggraaf, J D, Eijk, P P, Verhoef, C, Ylstra, B, Meijer, G A, van de Wiel, M A, Buffart, T E & Verheul, H M W 2018, ' Combination of a six microRNA expression profile with four clinicopathological factors for response prediction of systemic treatment in patients with advanced colorectal cancer ', PLoS ONE, vol. 13, no. 8, e0201809, pp. 1-20 . https://doi.org/10.1371/journal.pone.0201809 Neerincx, M, Poel, D, Sie, D L S, van Grieken, N C T, Shankaraiah, R C, van der Wolf-de Lijster, F S W, van Waesberghe, J-H T M, Burggraaf, J-D, Eijk, P P, Verhoef, C, Ylstra, B, Meijer, G A, van de Wiel, M A, Buffart, T E & Verheul, H M W 2018, ' Combination of a six microRNA expression profile with four clinicopathological factors for response prediction of systemic treatment in patients with advanced colorectal cancer ', PLoS ONE, vol. 13, no. 8, pp. e0201809 . https://doi.org/10.1371/journal.pone.0201809 |
ISSN: | 1932-6203 |
DOI: | 10.1371/journal.pone.0201809 |
Popis: | BACKGROUND: First line chemotherapy is effective in 75 to 80% of patients with metastatic colorectal cancer (mCRC). We studied whether microRNA (miR) expression profiles can predict treatment outcome for first line fluoropyrimidine containing systemic therapy in patients with mCRC.METHODS: MiR expression levels were determined by next generation sequencing from snap frozen tumor samples of 88 patients with mCRC. Predictive miRs were selected with penalized logistic regression and posterior forward selection. The prediction co-efficients of the miRs were re-estimated and validated by real-time quantitative PCR in an independent cohort of 81 patients with mCRC.RESULTS: Expression levels of miR-17-5p, miR-20a-5p, miR-30a-5p, miR-92a-3p, miR-92b-3p and miR-98-5p in combination with age, tumor differentiation, adjuvant therapy and type of systemic treatment, were predictive for clinical benefit in the training cohort with an AUC of 0.78. In the validation cohort the addition of the six miR signature to the four clinicopathological factors demonstrated a significant increased AUC for predicting treatment response versus those with stable disease (SD) from 0.79 to 0.90. The increase for predicting treatment response versus progressive disease (PD) and for patients with SD versus those with PD was not significant. in the validation cohort. MiR-17-5p, miR-20a-5p and miR-92a-3p were significantly upregulated in patients with treatment response in both the training and validation cohorts.CONCLUSION: A six miR expression signature was identified that predicted treatment response to fluoropyrimidine containing first line systemic treatment in patients with mCRC when combined with four clinicopathological factors. Independent validation demonstrated added predictive value of this miR-signature for predicting treatment response versus SD. However, added predicted value for separating patients with PD could not be validated. The clinical relevance of the identified miRs for predicting treatment response has to be further explored. |
Databáze: | OpenAIRE |
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