RhoB Determines Tumor Aggressiveness in a Murine EGFRL858R-Induced Adenocarcinoma Model and Is a Potential Prognostic Biomarker for Lepidic Lung Cancer
| Autor: | Isabelle Rouquette, Thomas Filleron, Gilles Favre, Anne Casanova, Julien Mazieres, Olivier Calvayrac, Isabelle Raymond-Letron, Michèle Beau-Faller, Valérie Lauwers-Cances, Emilie Bousquet, Jacques Cadranel, Julie Milia, Anne Pradines |
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| Přispěvatelé: | Centre de Recherches en Cancérologie de Toulouse (CRCT), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Genetically modified mouse Cancer Research Pathology medicine.medical_specialty Lung Neoplasms [SDV]Life Sciences [q-bio] RHOB Gene Expression Adenocarcinoma of Lung Mice Transgenic Adenocarcinoma Mice Risk Factors Biomarkers Tumor medicine Animals Humans Prognostic biomarker rhoB GTP-Binding Protein Lung cancer Aged Neoplasm Staging Mice Knockout Lung business.industry Cancer Middle Aged Prognosis medicine.disease Tumor Burden respiratory tract diseases 3. Good health ErbB Receptors Disease Models Animal Cell Transformation Neoplastic medicine.anatomical_structure Oncology Mutation Disease Progression Cancer research Immunohistochemistry Female business |
| Zdroj: | Clinical Cancer Research Clinical Cancer Research, American Association for Cancer Research, 2014, 20 (24), pp.6541-6550. ⟨10.1158/1078-0432.CCR-14-0506⟩ |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: A crucial event in lung adenocarcinoma progression is the switch from an aerogenous spread toward an infiltrating tumor. Loss of RhoB expression has been suggested to be critical for lung cancer invasion. Here, we tested RhoB expression as a prognostic biomarker in non–small cell lung cancer (NSCLC) with a special focus on lepidic pattern. Experimental Design: We analyzed RhoB expression using both IHC and RT-qPCR in two series of operated patients (n = 100 and 48, respectively) and in a series of advanced lepidic adenocarcinoma (n = 31) from different hospitals. Next, we examined the role of RhoB in lung cancer progression in transgenic mice that express inducible EGFRL858R crossed with Rhob null mice. Results: We identified that loss of RhoB expression was strongly associated with worse survival (P = 0.0001) and progression-free survival (P < 0.001) in the first series. We then confirmed these results after multivariate analyses of the second series. In the series of adenocarcinoma with lepidic features issued from a clinical trial (IFCT-0401), we showed that loss of RhoB expression was associated with higher aggressiveness of stage IV. Finally, we showed that EGFRL858R/Rhob+/+ mice developed mainly diffuse lung tumors with a lepidic pattern, whereas EGFRL858R/Rhob+/− and EGFRL858R/Rhob−/− developed a greater number of tumors, and aggressive adenocarcinomas with invasive properties. Conclusions: We showed that RhoB is not only a strong prognostic factor in NSCLC but it is also critical for the acquisition of an aggressive phenotype of adenocarcinoma. Clin Cancer Res; 20(24); 6541–50. ©2014 AACR. |
| Databáze: | OpenAIRE |
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