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

Zhou, Qimin (författare)
Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lever-, pankreas- och gallvägskirurgi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Hepato-Pancreato-Biliary Surgery,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital,Wenzhou Medical University
Bauden, Monika (författare)
Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lever-, pankreas- och gallvägskirurgi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Hepato-Pancreato-Biliary Surgery,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
Andersson, Roland (författare)
Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lever-, pankreas- och gallvägskirurgi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Hepato-Pancreato-Biliary Surgery,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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Hu, Dingyuan (författare)
Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
Marko-Varga, György (författare)
Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Lund University Research Groups
Xu, Jianfeng (författare)
Wenzhou Medical University
Sasor, Agata (författare)
Skåne University Hospital
Dai, Hua (författare)
Nanchang University
Pawłowski, Krzysztof (författare)
Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Masspektrometri,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Protein Science and Imaging,Clinical Chemistry, Malmö,Lund University Research Groups,Mass Spectrometry,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
Said Hilmersson, Katarzyna (författare)
Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
Chen, Xi (författare)
Wenzhou Medical University
Ansari, Daniel (författare)
Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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 (creator_code:org_t)
2020-02-13
2020
Engelska.
Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 18, s. 1-10
Relaterad länk:
http://dx.doi.org/10... (free)
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https://translationa...
https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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 a significant correlation between mRNA expression level data and reduced overall survival (p = 0.001). In addition, TMA and immunohistochemistry analysis suggested that YAP1 protein expression is an independent predictor of poor overall survival [hazard ratio (HR) 1.870, 95% confidence interval (CI) 1.224-2.855, p = 0.004], as well as reduced disease-free survival (HR 1.950, 95% CI 1.299-2.927, p = 0.001). Bioinformatic analyses coupled with in vitro assays indicated that YAP1 is involved in the transcriptional control of target genes, associated with extracellular matrix remodeling, which could be modified by selected substances disrupting the YAP1-TEAD interaction.CONCLUSIONS: Our findings indicate that YAP1 is an important prognostic biomarker for pancreatic cancer and may play a regulatory role in the remodeling of the extracellular matrix.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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