title: A microRNA signature predicts survival in early stage small-cell lung cancer treated with surgery and adjuvant chemotherapy.
abstract: Small-cell lung cancer (SCLC) is one of the most aggressive cancers, yet the molecular mechanisms underlying its devastating clinical outcome remain elusive. In this study, we investigated whether microRNA (miRNA) expression profiles can predict the clinical outcomes of SCLC patients. A total of 82 patients with limited SCLC, who were treated with surgical resection and adjuvant chemotherapy, were enrolled in this study. First, we surveyed the expression of 924 miRNAs from 42 SCLC patients to discover survival-relevant miRNAs and develop prognostic models, which were then validated in an independent cohort of 40 cases using quantitative real-time PCR. We found that the miR-150/miR-886-3p signature was significantly correlated with the overall survival (OS) of SCLC patients (p = 0.02) in the training set, and both miRNA expression levels were much lower in the SCLC samples than normal lung samples. The miRNA signature also proved to be a significant predictor of survival in the validation set. Patients with high-risk miRNA signatures had poor overall survival (p = 0.005) and progression-free survival (p = 0.017) compared with those with low-risk scores. These findings retained statistical significance after adjusting for age, gender and smoking status (HR: 0.26, 95%: CI 0.10-0.69, p = 0.007), which suggested it may be an independent predictor of survival. In summary, we developed a prognostic miR-150/miR-886-3p signature and validated expression in an independent dataset of resectable SCLC. These preliminary results indicated that miRNAs may serve as promising molecular prognostic markers and new therapeutic targets for SCLC.
authors.affiliation: Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Bi
authors.affiliation: Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wenyang
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Thoracic Surgery, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Medical Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pathology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Luhua
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D059467:Transcriptome
chemical_list: D035683:MicroRNAs