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Master Thesis

Expression de la protéine TFE3 dans les carcinomes rénaux à cellules claires : exploration d’une nouvelle voie d’oncogenèse

Abstract : Objectives: to comprehensively investigate the role of Transcription factor E3 (TFE3) protein in clear cell renal cell carcinoma (ccRCC), with respect to prognostic value and biomarker potential. Patients and methods: TFE3 and c-MET Immunohistochemistry (IHCs) were performed on 66 cases of ccRCC of the Centre hospitalier universitaire (CHU) de Nice and were separated into low and high expressing (Allred low and high) groups. The levels of messenger ribonucleic acid (mRNA) expression of TFE3, MET and LEF1 were assayed on a French cohort (Nice + Rennes + Bordeaux) comprising 166 cases of ccRCC. The correlations between each protein as well as different clinical data (Tumor nodes metastasis (TNM), disease free survival, overall survival) were compared for each group. We used a The Cancer Genome Atlas (TCGA) cohort comprising 434 ccRCC and 14 tRCC cases as a validation cohort. Results: in the Nice cohort, 46 cases (69.7%) were TFE3 Allred low and 20 cases (30.3%) were TFE3 Allred high in IHC. The level of IHC expression was correlated with the level of mRNA expression (p=0.0023). Disease-free survival (DFS) was reduced in the Allred high group (p=0.0197), and the TFE3 mRNA high group (p=0.0088), which was confirmed by the TCGA cohort analysis (p=0.0005 for DFS/PFS and p<0.0001 for OS). Among MiTF family transcription factors potentially involved in the overexpression of TFE3 in ccRCC, TCGA cohort analysis revealed LEF1 as one of the main (p<0.0001), confirmed by the French cohort (p<0.0001). ccRCC overexpressing LEF1 in the French cohort were correlated with reduced Disease free survival (DFS) and Overall survival (OS) (p=0.0457 and p=0.004, respectively). These results were confirmed by the analysis of the TCGA cohort for DFS (p=0.0012). Furthermore, analysis of c-MET IHC expression (h-score) was correlated to LEF1 mRNA expression (p=0.011) in the Nice cohort. TFE3 overexpression was then correlated to MET mRNA in the French cohort (p=0.0082). TFE3 overexpression was also correlated to Podoplanin mRNA, a specific lymphatic vessel marker, in the French and TCGA cohort (p=0.0133 and p<0.0001, respectively). Conclusions: CcRCC can overexpress TFE3 in IHC in the absence of translocation. The LEF1 protein plays a crucial role in the overexpression of TFE3, which is responsible for activating MET transcription and the corresponding HGF / c-MET signaling pathway, resulting in a more aggressive tumor with activated lymphatic proliferation.
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Master Thesis
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Submitted on : Wednesday, January 5, 2022 - 9:10:24 AM
Last modification on : Thursday, January 6, 2022 - 3:15:11 AM
Long-term archiving on: : Wednesday, April 6, 2022 - 6:36:20 PM


  • HAL Id : dumas-03511659, version 1


Youta Fanjat. Expression de la protéine TFE3 dans les carcinomes rénaux à cellules claires : exploration d’une nouvelle voie d’oncogenèse. Médecine humaine et pathologie. 2020. ⟨dumas-03511659⟩



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