%0 Journal Article
%T A transcriptional MAPK Pathway Activity Score (MPAS) is a clinically relevant biomarker in multiple cancer types
%A Bonnie Liu
%A Christiaan Klijn
%A Daniel Kirouac
%A Garret Hampton
%A John Moffat
%A Kwame Okrah
%A Ling Huw
%A Lukas Amler
%A Marie-Claire Wagle
%A Mark Merchant
%A Mark R. Lackner
%A Matthew Wongchenko
%A Melissa Junttila
%A Omar Kabbarah
%A Peter M. Haverty
%A Robert L. Yauch
%A Saroja Ramanujan
%A Shih-Min A. Huang
%A Shilpi Mahajan
%A Shrividhya Srinivasan
%A Teiko Sumiyoshi
%A Yibing Yan
%A Zineb Mounir
%J Archive of "NPJ Precision Oncology".
%D 2018
%R 10.1038/s41698-018-0051-4
%X Aggregated gene expression data from a set of 10 MAPK-specific genes predicts MEK inhibitor sensitivity. a MPAS and corresponding cell viability data (relative to vehicle (DMSO) control on day of treatment) in response to 0每10ˋ米M cobimetinib treatment for 72ˋh in melanoma (MEL-JUSO), NSCLC (NCI-H2347), and pancreatic (HUP-T4) cell lines. Error bars represent standard deviation across triplicate samples. Correlations of MPAS vs. relative cell growth for each cell line are also shown. b Rank correlation coefficients (filtered for Pˋ<ˋ0.05) between MPAS and sensitivity (mean viabilities) to MAPK and PI3K signaling pathway inhibitors across cell lines from breast (BRCA) (nˋ=ˋ36), lung (nˋ=ˋ95), CRC (colorectal) (nˋ=ˋ50), melanoma (nˋ=ˋ40), pancreatic (nˋ=ˋ36), and all indications (pan-cancer) (nˋ=ˋ506). c E-Net model-based prediction of cobimetinib sensitivity (1-MV Predicted) for 40 independent NSCLC cell lines vs. the actual mean viabilities (1-MV Data) for the same cell lines treated with 0每10ˋ米M cobimetinib for 72ˋh. MPAS vs. actual cobimetinib sensitivity (1-MV Data) for the same cell lines treated with 0每10ˋ米M cobimetinib for 72ˋh. d 40 NSCLC cell lines were categorized as either ※sensitive§ IC50ˋ<ˋ1ˋ米M or ※resistant§ IC50ˋ>ˋ1ˋ米M to cobimetinib. True positive (TPR, TPRˋ=ˋTP/(TPˋ+ˋFN)), false positive rate (FPRˋ=ˋFP/(FPˋ+ˋTN)), and accuracy (ACCˋ=ˋ(TPˋ+ˋTN)/N) were computed using median-based classification of the E-Net predictions and MPAS and compared to CTRL score (house-keeping gene expression), KRAS mutation status, and mean viability. e The cumulative distribution of Spearman correlation coefficients for 45 team＊s predictions of MEK1/2 inhibitor (PD184352) sensitivity from the DREAM consortium Drug Sensitivity Challenge, compared to the performance of the elastic net model, (老ˋ=ˋ0.55) mapping to the 36th percentile, and the MAPK score (老ˋ=ˋ0.65), to the 28th percentil
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871852/