公开(公告)号：US20240316005A1

公开(公告)日：2024-09-26

申请号：US18575431

申请日：2022-07-04

申请人： INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE ,  UNIVERSITÉ DE BORDEAUX ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  UNIVERSITÉ COTE D'AZUR

发明人： Andreas BIKFALVI ,  Wilfried SOULEYREAU ,  Lindsay COOLEY ,  Marie NIKOLSKI ,  Justine RUDEWICZ ,  Gilles PAGES ,  Maeva DUFIES

IPC分类号： A61K31/404 ,  A61K39/395 ,  A61P35/00 ,  C07K16/28 ,  C12Q1/6886

CPC分类号： A61K31/404 ,  A61K39/3955 ,  A61P35/00 ,  C07K16/2818 ,  C12Q1/6886 ,  C07K2317/21 ,  C12Q2600/118 ,  C12Q2600/158

摘要： Renal Cell Carcinoma (RCC) is difficult to treat with 5-year survival rate of 10% in metastatic patients. Main reasons of therapy failure are lack of validated biomarkers and scarce knowledge of the biological processes occurring during RCC progression. Thus, the investigation of mechanisms regulating RCC progression is fundamental to improve RCC therapy. In order to identify molecular markers and gene processes involved in the steps of RCC progression, the inventors generated several cell lines of higher aggressiveness by serially passaging mouse renal cancer RENCA cells in mice and, concomitantly, performed functional genomics analysis of the cells. Multiple cell lines depicting the major steps of tumor progression (including primary tumor growth, survival in the blood circulation and metastatic spread) were generated and analyzed by large-scale transcriptome, genome and methylome analyses. Importantly, transcriptome analysis revealed distinct signatures of tumor aggressiveness which were validated in the TCGA-KIRC cohort. The signatures are particularly suitable for determining the survival time of the patients and predicting response to the therapies.