title: Comparison of the Prognostic Utility of the Diverse Molecular Data among lncRNA, DNA Methylation, microRNA, and mRNA across Five Human Cancers.
abstract: BACKGROUND
  Advances in high-throughput technologies have generated diverse informative molecular markers for cancer outcome prediction. Long non-coding RNA (lncRNA) and DNA methylation as new classes of promising markers are emerging as key molecules in human cancers; however, the prognostic utility of such diverse molecular data remains to be explored.
  
  
  METHODS
  We proposed a computational pipeline (IDFO) to predict patient survival by identifying prognosis-related biomarkers using multi-type molecular data (mRNA, microRNA, DNA methylation, and lncRNA) from 3198 samples of five cancer types. We assessed the predictive performance of both single molecular data and integrated multi-type molecular data in patient survival stratification, and compared their relative importance in each type of cancer, respectively. Survival analysis using multivariate Cox regression was performed to investigate the impact of the IDFO-identified markers and traditional variables on clinical outcome.
  
  
  RESULTS
  Using the IDFO approach, we obtained good predictive performance of the molecular datasets (bootstrap accuracy: 0.71-0.97) in five cancer types. Impressively, lncRNA was identified as the best prognostic predictor in the validated cohorts of four cancer types, followed by DNA methylation, mRNA, and then microRNA. We found the incorporating of multi-type molecular data showed similar predictive power to single-type molecular data, but with the exception of the lncRNA + DNA methylation combinations in two cancers. Survival analysis of proportional hazard models confirmed a high robustness for lncRNA and DNA methylation as prognosis factors independent of traditional clinical variables.
  
  
  CONCLUSIONS
  Our study provides insight into systematically understanding the prognostic performance of diverse molecular data in both single and aggregate patterns, which may have specific reference to subsequent related studies.
authors.affiliation: School of life science and biotechnology, Harbin Institute of Technology, Harbin, Hei Longjiang Province, China.|State Key Laboratory of Space Medicine Fundamentals and Application, Space Institute of Southern China, China Astronaut Research and Training Center, Beijing, China.|National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, Space Institute of Southern China, China Astronaut Research and Training Center, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Fengji
authors.affiliation: Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Yunnan, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Changning
authors.affiliation: Department of statistics, Rice University, Houston, Texas, United States of America.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Liangcai
authors.affiliation: School of life science and biotechnology, Harbin Institute of Technology, Harbin, Hei Longjiang Province, China.|State Key Laboratory of Space Medicine Fundamentals and Application, Space Institute of Southern China, China Astronaut Research and Training Center, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yinghui
authors.affiliation: School of life science and biotechnology, Harbin Institute of Technology, Harbin, Hei Longjiang Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: School of life science and biotechnology, Harbin Institute of Technology, Harbin, Hei Longjiang Province, China.|National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shanguang
authors.affiliation: State Key Laboratory of Space Medicine Fundamentals and Application, Space Institute of Southern China, China Astronaut Research and Training Center, Beijing, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Jianghui
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D014594:Uterine Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger