title: Plasma miRNAs in predicting radiosensitivity in non-small cell lung cancer.
abstract: BACKGROUND
  Radioresistance of thoracic radiotherapy is a major bottleneck in the treatment of non-small cell lung cancer (NSCLC). Until now, there have been no effective biomarkers to predict the radiosensitivity.
  
  
  OBJECTIVE
  Based on miRNA profile screened from NSCLC cell lines with different radiosensitivity, this study was conducted to explore the correlation between plasma miRNAs and radiotherapy response in NSCLC patients, and to identify biomarkers of the radiosensitivity in NSCLC.
  
  
  METHODS
  Differentially expressed genes were acquired from time-series gene expression profiles of radioresistant H1299 and radiosensitive H460 lung cancer cells (GSE20549). Potential miRNAs were screened from these differentially expressed genes by combining bioinformatics with GO analysis, pathway analysis, and miRNA prediction. A clinical observational study was performed to explore the correlation between candidate miRNAs and radiotherapy response. Stage IIIa-IV NSCLC patients who received two to four cycles of previous chemotherapy and underwent thoracic radiotherapy alone were included. Total RNA was purified from peripheral blood before radiotherapy, and plasma miRNAs were detected by real-time PCR (qRT-PCR). Then, tumor response, progression-free survival (PFS), and overall survival (OS) were acquired. Four miRNAs significantly different between effective and ineffective groups were further analyzed to obtain cutpoints from receiver operating characteristic (ROC) curves and the predictive value of radiosensitivity.
  
  
  RESULTS
  Candidate miRNAs included 14 miRNAs screened from radioresistant genes and five from radiosensitive genes. From Jan., 2013 to Dec., 2014, 54 eligible patients were enrolled with a median follow-up of 15.3 months (range 4.6 to 31.4) by the deadline of Aug. 31, 2015. Totally, there were no case of complete response (CR), 15 of partial response (PR), 35 of stable disease (SD), and 4 of progressive disease (PD). Eight patients had no progression and 19 patients were still alive. The median PFS and OS were 6.6 months (range 2.3 to 29.3) and 15.3 months (range 4.6 to 31.4), respectively. Four miRNAs (hsa-miR-98-5p, hsa-miR-302e, hsa-miR-495-3p, and hsa-miR-613) demonstrated a higher expression in effective group (CR + PR, 15 cases) than in ineffective group (SD + PD, 39 cases). Based on each cutpoint, objective response rate (ORR) was higher in miR-high group than in miR-low group. No miRNA showed correlation with median PFS or OS.
  
  
  CONCLUSIONS
  Bioinformatical analysis and clinical verification reveal the correlation between plasma miRNAs and radiosensitivity in NSCLC patients. Plasma miRNAs represent novel biomarkers to predict radiotherapy response clinically.
authors.affiliation: Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Oncology Department, Leshan People's Hospital, Leshan, Sichuan, 614000, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Xingyun
authors.initials: X
authors.lastname: Liao
authors.affiliation: Medical English Department, College of Basic Medicine, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Rongxia
authors.initials: R
authors.lastname: Liao
authors.affiliation: Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Luping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Niu
authors.affiliation: Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Li
authors.affiliation: Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Zhengtang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. cqxqyy@foxmail.com.
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Cancer Institute of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. sunjg09@aliyun.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000532:radiotherapy; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D011836:Radiation Tolerance / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: Bioinformatics; Biomarker; NSCLC; Plasma; Radiosensitivity; miRNAs