Fig. 4.

ASCL1 ChIP-Seq analysis delineates downstream targets. (A) Base coverage plot of the 912 consensus peaks in all five ASCL1(+) cell lines. The base coverage in a 1,000-bp window is centered on the summits of the 912 consensus peaks collected at a 10-bp resolution and averaged for each cell line. The vertical axis is the normalized average base coverage of the consensus peaks, and the horizontal axis is the position relative to the summit. (B) Venn diagram showing peak-level overlap for all five ASCL1(+) samples along with the E-box binding site for each sample, as well as the consensus E-box binding site. Peak-level heterogeneity between samples is evident. (C) The 72-gene ASCL1 expression signature clustering analysis groups 9/10 of the NE-NSCLC cell lines separate from the typical NSCLC lines. (D) The ASCL1-associated 72-gene signature correlates with poor survival in retrospective analyses of lung adenocarcinoma patient datasets. Patients more likely to express the gene signature have poorer 5-y outcomes. (Upper) P < 0.0001, Gehan–Breslow–Wilcoxon test. (Lower) P < 0.0302, Gehan–Breslow–Wilcoxon test.