YAP1 is an independent prognostic marker in pancreatic cancer and associated with extracellular matrix remodeling

作者：Qimin Zhou, Monika Bauden, Roland Andersson, Dingyuan Hu, György Marko‐Varga, Jianfeng Xu, Agata Sasor, Hua Dai, Krzysztof Pawłowski, Katarzyna Said Hilmersson, Xi Chen, Daniel Ansari · 发表于：Journal of Translational Medicine · 年份：2020 · DOI：10.1186/s12967-020-02254-7 · 被引用次数：55 · 研究领域：Hippo pathway signaling and YAP/TAZ、FOXO transcription factor regulation、Cancer Cells and Metastasis

BACKGROUND: Pancreatic cancer is a major cause of cancer-related mortality. The identification of effective biomarkers is essential in order to improve management of the disease. Yes-associated protein 1 (YAP1) is a downstream effector of the Hippo pathway, a signal transduction system implicated in tissue repair and regeneration, as well as tumorigenesis. Here we evaluate the biomarker potential of YAP1 in pancreatic cancer tissue. METHODS: YAP1 was selected as a possible biomarker for pancreatic cancer from global protein sequencing of fresh frozen pancreatic cancer tissue samples and normal pancreas controls. The prognostic utility of YAP1 was evaluated using mRNA expression data from 176 pancreatic cancer patients in The Cancer Genome Atlas (TCGA), as well as protein expression data from immunohistochemistry analysis of a local tissue microarray (TMA) cohort comprising 140 pancreatic cancer patients. Ingenuity Pathway Analysis was applied to outline the interaction network for YAP1 in connection to the pancreatic tumor microenvironment. The expression of YAP1 target gene products was evaluated after treatment of the pancreatic cancer cell line Panc-1 with three substances interrupting YAP-TEAD interaction, including Super-TDU, Verteporfin and CA3. RESULTS: Mass spectrometry based proteomics showed that YAP1 is the top upregulated protein in pancreatic cancer tissue when compared to normal controls (log2 fold change 6.4; p = 5E-06). Prognostic analysis of YAP1 demonstrated...