LAUSR

Background: The advancement of targeted drugs for blocking tumor driving signaling pathway(s) is expected to lead to improved outcome for cancer patients. However, a critical requirement for that is reliable and accurate diagnostics on activity of oncogenic signaling pathways. A novel analysis method, based on Bayesian network-based inference of signaling pathway activity from levels of target gene mRNAs of the pathway-associated transcription factor, was developed to infer pathway activity from mRNA expression data [1], with which we previously reported that the WNT [1] and PI3K pathway [2] become active in colon carcinomas. Methods. Public datasets from the Gene Expression Omnibus, measured with the Affymetrix U133 Plus 2.0 platform, were analyzed for signaling pathway activity scores, among which are the MAPK-AP1, and TGFβ pathways. Colon tissue samples have been classified using the Consensus Molecular Subtypes of colorectal cancer classification (CMS). [3] Results. WNT and PI3K pathway activity were increased in colon carcinomas as reported before. The signaling pathway activity described by the CMS classification was confirmed using pathway activity analysis, TGFβ pathway activity was highest in the bad prognosis CMS4 subtype. A Kaplan-Meier curve shows higher TGFβ pathway activity to be associated with lower survival chance (p Citation Format: Yvonne Wesseling-Rozendaal, Paul van Swinderen, Julie Gil, Sieglinde Neerken, Anja van de Stolpe. Quantitative measurements of functional activity of the TGFβ and MAPK-AP1 pathways in colon cancer provides information on their role in cancer development and metastasis [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C020. doi:10.1158/1535-7163.TARG-19-C020