title: MiRNA Expression Analysis of Pretreatment Biopsies Predicts the Pathological Response of Esophageal Squamous Cell Carcinomas to Neoadjuvant Chemoradiotherapy.
abstract: OBJECTIVE
  To identify miRNA markers useful for esophageal squamous cell carcinoma (ESCC) neoadjuvant chemoradiotherapy (neo-CRT) response prediction.
  
  
  CONCLUSIONS
  Neo-CRT followed by surgery improves ESCC patients' survival compared with surgery alone. However, CRT outcomes are heterogeneous, and no current methods can predict CRT responses.
  
  
  METHODS
  Differentially expressed miRNAs between ESCC pathological responders and nonresponders after neo-CRT were identified by miRNA profiling and verified by real-time quantitative polymerase chain reaction (qPCR) of 27 ESCCs in the training set. Several class prediction algorithms were used to build the response-classifying models with the qPCR data. Predictive powers of the models were further assessed with a second set of 79 ESCCs.
  
  
  RESULTS
  Ten miRNAs with greater than a 1.5-fold change between pathological responders and nonresponders were identified and verified, respectively. A support vector machine (SVM) prediction model, composed of 4 miRNAs (miR-145-5p, miR-152, miR-193b-3p, and miR-376a-3p), were developed. It provided overall accuracies of 100% and 87.3% for discriminating pathological responders and nonresponders in the training and external validation sets, respectively. In multivariate analysis, the subgroup determined by the SVM model was the only independent factor significantly associated with neo-CRT response in the external validation sets.
  
  
  CONCLUSIONS
  Combined qPCR of the 4 miRNAs provides the possibility of ESCC neo-CRT response prediction, which may facilitate individualized ESCC treatment. Further prospective validation in larger independent cohorts is necessary to fully assess its predictive power.
authors.affiliation: *State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China †Guangdong Esophageal Cancer Institute Guangzhou, China ‡Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China §Department of Radiotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China ¶Guangzhou Haige Communications Group Incorporated Company, Guangzhou, China ||School of Electronic & Information Engineering, South China University of Technology, Guangzhou, China **Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, Shantou, China ††Department of Radiotherapy, Cancer Hospital of Shantou University Medical College, Shantou, China ‡‡Department of Anesthesiology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.forename: Kongjia
authors.initials: K
authors.lastname: Luo
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Shiliang
authors.initials: S
authors.lastname: Liu
authors.forename: Guangrong
authors.initials: G
authors.lastname: Lin
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Geng
authors.initials: G
authors.lastname: Wang
authors.forename: Yuping
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.forename: Xiuying
authors.initials: X
authors.lastname: Xie
authors.forename: Mengzhong
authors.initials: M
authors.lastname: Liu
authors.forename: Huiyun
authors.initials: H
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Fu
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D004938:Esophageal Neoplasms / Q000473:pathology / Q000628:therapy*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D060388:Support Vector Machine; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs