A Novel Algorithm for Simplification of Complex Gene Classifiers in Cancer

作者：Wilson Raphael A; Teng Ling; Bachmeyer Karen M; Bissonnette Mei Lin Z; Husain Aliya N; Parham David M; Triche Timothy J; Wing Michele R; Gastier Foster Julie M; Barr Frederic G; Hawkins Douglas S; Anderson James R; Skapek Stephen X; Volchenboum Samuel L^*

来源：Cancer Research, 2013, 73(18): 5625-5632.

DOI：10.1158/0008-5472.CAN-13-0324

The clinical application of complex molecular classifiers as diagnostic or prognostic tools has been limited by the time and cost needed to apply them to patients. Using an existing 50-gene expression signature known to separate two molecular subtypes of the pediatric cancer rhabdomyosarcoma, we show that an exhaustive iterative search algorithm can distill this complex classifier down to two or three features with equal discrimination. We validated the two-gene signatures using three separate and distinct datasets, including one that uses degraded RNA extracted from formalin-fixed, paraffin-embedded material. Finally, to show the generalizability of our algorithm, we applied it to a lung cancer dataset to find minimal gene signatures that can distinguish survival. Our approach can easily be generalized and coupled to existing technical platforms to facilitate the discovery of simplified signatures that are ready for routine clinical use.

• 出版日期2013-9-15