title: RNA sequencing validation of the Complexity INdex in SARComas prognostic signature.
abstract: BACKGROUND
  Prognosis of metastatic outcome in soft tissue sarcomas is an important clinical challenge since these tumours can be very aggressive (up to 50% of recurring events). A gene expression signature, Complexity INdex in SARComas (CINSARC), has been identified as a better prognostic factor compared to the current international grading system defined by the Fédération Nationale des Centres de Lutte Contre le Cancer. Since CINSARC has been established on frozen tumours analysed by microarrays, we were interested in evaluating its prognostic capacity using next generation sequencing (NGS) on formalin-fixed, paraffin-embedded (FFPE) blocks to better fit laboratory practices.
  
  
  METHODS
  Metastatic-free survivals (training/validation approach with independent datasets) and agreement values in classification groups were evaluated. Also, RNA degradation threshold has been established for FFPE blocks and differences in gene expression due to RNA degradation were measured.
  
  
  RESULTS
  CINSARC remains a strong prognostic factor for metastatic outcome in both microarray and RNA-seq technologies (P < 0.05), with similar risk-group classifications (77%). We defined quality threshold to process degraded RNA extracted from FFPE blocks and measured similar classifications with frozen tumours (88%).
  
  
  CONCLUSIONS
  These results demonstrate that CINSARC is a platform and material independent prognostic signature for metastatic outcome in various sarcomas. This result opens access to metastatic prognostication in sarcomas through NGS analysis on both frozen and FFPE tumours via the CINSARC signature.
authors.affiliation: Inserm U916, Institut Bergonié, Bordeaux, France; Aquitaine Science Transfert, Centre Condorcet, Pessac, France; Site de Recherche Intégrée sur le Cancer, Bordeaux Recherche Intégrée en Oncologie, Bordeaux, France.
authors.forename: Tom
authors.initials: T
authors.lastname: Lesluyes
authors.affiliation: Inserm U916, Institut Bergonié, Bordeaux, France; Département de pathologie, Institut Bergonié, Bordeaux, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pérot
authors.affiliation: Inserm U916, Institut Bergonié, Bordeaux, France; Aquitaine Science Transfert, Centre Condorcet, Pessac, France.
authors.forename: Marine Roxane
authors.initials: MR
authors.lastname: Largeau
authors.affiliation: Inserm U916, Institut Bergonié, Bordeaux, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Brulard
authors.affiliation: Inserm U916, Institut Bergonié, Bordeaux, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Lagarde
authors.affiliation: Département de pathologie, Institut Bergonié, Bordeaux, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Dapremont
authors.affiliation: Inserm U916, Institut Bergonié, Bordeaux, France; Site de Recherche Intégrée sur le Cancer, Bordeaux Recherche Intégrée en Oncologie, Bordeaux, France.
authors.forename: Carlo
authors.initials: C
authors.lastname: Lucchesi
authors.affiliation: Inserm U916, Institut Bergonié, Bordeaux, France; Département de pathologie, Institut Bergonié, Bordeaux, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Neuville
authors.affiliation: Département de pathologie, Institut Gustave Roussy, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Terrier
authors.affiliation: Département de pathologie, Centre Léon Bérard, Lyon, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Vince-Ranchère
authors.affiliation: Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Mendez-Lago
authors.affiliation: Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Gut
authors.affiliation: Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.affiliation: Inserm U916, Institut Bergonié, Bordeaux, France; Département de pathologie, Institut Bergonié, Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Coindre
authors.affiliation: Inserm U916, Institut Bergonié, Bordeaux, France; Département de pathologie, Institut Bergonié, Bordeaux, France. Electronic address: f.chibon@bordeaux.unicancer.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chibon
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D020869:Gene Expression Profiling / Q000592:standards; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics* / Q000401:mortality; D017423:Sequence Analysis, RNA / Q000379:methods*; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000401:mortality
chemical_list: D012334:RNA, Neoplasm
keywords: Cancer; High-throughput RNA sequencing; Metastasis; Sarcoma; Transcriptome