RNA sequencing validation of the Complexity INdex in SARComas prognostic signature

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%).

Conclusion: 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.