1. Oncogenic role of PMEPA1 and its association with immune exhaustion and TGF-β activation in HCC
- Author
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Marta Piqué-Gili, Carmen Andreu-Oller, Agavni Mesropian, Roger Esteban-Fabró, Marina Bárcena-Varela, Marina Ruiz de Galarreta, Carla Montironi, Iris Martinez-Quetglas, Sarah Cappuyns, Judit Peix, Ieva Keraite, Albert Gris-Oliver, Elisa Fernández-Martínez, Ezequiel Mauro, Miguel Torres-Martin, Jordi Abril-Fornaguera, Katherine E. Lindblad, Diether Lambrechts, Jeroen Dekervel, Swan N. Thung, Daniela Sia, Amaia Lujambio, Roser Pinyol, and Josep M. Llovet
- Subjects
HCC ,oncogene ,TGF-β signalling ,genetically engineered mouse model ,GEMM ,immune exhaustion ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Transforming growth factor β (TGF-β) plays an oncogenic role in advanced cancer by promoting cell proliferation, metastasis and immunosuppression. PMEPA1 (prostate transmembrane protein androgen induced 1) has been shown to promote TGF-β oncogenic effects in other tumour types. Thus, we aimed to explore the role of PMEPA1 in hepatocellular carcinoma (HCC). Methods: We analysed 1,097 tumours from patients with HCC, including discovery (n = 228) and validation (n = 361) cohorts with genomic and clinicopathological data. PMEPA1 levels were assessed by qPCR (n = 228), gene expression data (n = 869) and at the single-cell level (n = 54). Genetically engineered mouse models overexpressing MYC+PMEPA1 compared to MYC were generated and molecular analyses were performed on the HCCs obtained. Results: PMEPA1 was overexpressed in 18% of HCC samples (fold-change >2; n = 201/1,097), a feature associated with TGF-β signalling activation (p
- Published
- 2024
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