Traditional statistical methods often fail to identify biologically meaningful biomarkers from expression data alone. In this paper, we develop a novel strategy, namely knowledge-driven multi-level Independent Component Analysis (ICA), to infer regulatory signals and identify biomarkers based on clustering results and partial prior knowledge. A statistical test is designed to evaluate significance of transcription factor enrichment for extracted gene set based on motif information. The experimental results on an Rsf-1 (HBXAP) induced microarray data set show that our method can successfully extract biologically meaningful biomarkers related to ovarian cancer compared to other gene selection methods with or without prior knowledge.