Fig. 3
PARP1, RAD51, and BRCA1 expression and gene signatures as predictive markers of trabectedin and olaparib synergism. a, enrichment analysis of gene sets (GSEA) published in Molecular Signatures Database v5.0 of Broad Institute obtained by comparing mRNA expression profiles in cells displaying high combination synergism (HS-C: TC-106; DMR; 402.91) with cells displaying low/no synergy (LS-C: SJSA-1; HT1080; SW684) at basal condition (untreated) or after 24-h treatment with 1.25 nM trabectedin (TR), 1.25 μM olaparib (OL), or combination (CB); b, direct correlation (linear regression) between synergism of trabectedin and olaparib in combination (combination index) and mRNA expression (ΔCT) of PARP1, BRCA1, and RAD51 in 19 human sarcoma cell lines (as in Additional file 1: Table S3); Pearson score r and P value are indicated in blue, red and green for PARP1, BRCA1 and RAD51 respectively; c, western blot analysis and D, immunocytochemistry of PARP1, BRCA1, and RAD51 expression in TC-106, DMR, 402.91, SJSA-1, HT1080, and SW684