title: Identification of biomarker microRNAs for predicting the response of colorectal cancer to neoadjuvant chemoradiotherapy based on microRNA regulatory network.
abstract: Preoperative radiotherapy or chemoradiotherapy has become a standard procedure for treatment of patients with locally advanced colorectal cancer (CRC). However, patients' responses to treatment are different and personalized. MicroRNAs (miRNAs) are promising biomarkers for predicting personalized responses. In this study, we collected 30 publicly reported miRNAs associated with chemoradiotherapy of CRC. We extracted 46 differentially expressed miRNAs from samples of responders and non-responders to preoperative radiotherapy from the Gene Expression Omnibus dataset (Student's t test, p-value < 0.05 and |fold-change| > 2). We performed a systematic and integrative bioinformatics analysis to identify biomarker miRNAs for prediction of CRC responses to chemoradiotherapy. Using the bioinformatics model, miR-198, miR-765, miR-671-5p, miR-630, miR-371-5p, miR-575, miR-202, miR-483-5p and miR-513a-5p were screened as putative biomarkers for treatment response. Literature validation and functional enrichment analysis were exploited to confirm the reliability of the predicted miRNAs. Quantitative polymerase chain reaction showed that seven of the candidates were significantly differentially expressed between radiosensitive and insensitive CRC cell lines. The unique target genes of miR-198 and miR-765 were altered significantly upon transfection of specific miRNA mimics in the radiosensitive cell line. These results demonstrated the predictive power of our model and suggested that miR-198, miR-765, miR-630, miR-371-5p, miR-575, miR-202 and miR-513a-5p could be used for predicting the response of CRC to preoperative chemoradiotherapy.
authors.affiliation: Department of Radiotherapy and Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China.|Institute of Radiotherapy and Oncology, Soochow University, Suzhou, China.|Suzhou Key Laboratory for Radiation Oncology, Suzhou, China.
authors.forename: Yaqun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Radiotherapy and Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China.|Institute of Radiotherapy and Oncology, Soochow University, Suzhou, China.|Suzhou Key Laboratory for Radiation Oncology, Suzhou, China.
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Radiotherapy and Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China.|Institute of Radiotherapy and Oncology, Soochow University, Suzhou, China.|Suzhou Key Laboratory for Radiation Oncology, Suzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Radiotherapy and Oncology, Second Affiliated Hospital of Soochow University, Suzhou, China.|Institute of Radiotherapy and Oncology, Soochow University, Suzhou, China.|Suzhou Key Laboratory for Radiation Oncology, Suzhou, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Shen
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Min
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, China.|Institute of Biological Sciences and Biotechnology, Donghua University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: School of Chemistry, Biology and Material Engineering, Suzhou University of Science and Technology, Suzhou, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Center for Systems Biology, Soochow University, Suzhou, China.|Key laboratory of Systems Biology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Bairong
authors.initials: B
authors.lastname: Shen
mesh_terms: D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000302:isolation & purification; D059248:Chemoradiotherapy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics / Q000302:isolation & purification; D008991:Monitoring, Physiologic / Q000379:methods; D020360:Neoadjuvant Therapy
chemical_list: D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: bioinformatics model; biomarker microRNA; colorectal cancer; microRNA regulatory network; neoadjuvant chemoradiotherapy