Matches in SemOpenAlex for { <https://semopenalex.org/work/W3000620706> ?p ?o ?g. }
- W3000620706 abstract "Abstract Renal cell carcinoma (RCC) still lacks prognostic and predictive biomarkers to monitor the disease and the response to therapy. The usual strategy in translational research is to start from human samples, to identify molecular markers and gene networks and then to functionally validate them in vitro and in animal models. We devised herein a completely opposite strategy from “mouse to man” by performing an aggressiveness screen and used functional genomics, imaging, clinical data and computational approaches in order to discover molecular pathways and players in renal cancer development and metastasis. Multiple cell lines for primary tumor growth, survival in the blood circulation and lung metastasis or metastatic spread from the primary tumor were generated and analyzed using a multi-layered approach which includes large-scale transcriptome, genome and methylome analyses. Transcriptome and methylome analyses demonstrated distinct clustering in three different groups. Remarkably, DNA sequencing did not show significant genomic variations in the different groups which indicates absence of clonal selection during the in vivo amplification process. Transcriptome analysis revealed distinct signatures of tumor aggressiveness which were validated in patient cohorts. Methylome analysis of full-length DNA allowed clustering of the same groups and revealed clinically relevant signatures. Furthermore, we identified SAA2 and CFB as soluble prognostic and predictive biomarkers of the therapeutic response. We also uncovered IL34 as another soluble prognostic biomarker and key regulator of renal cell carcinoma (RCC) progression. This was also functionally validated in vivo, and a mathematical model of IL34-dependent primary tumor growth and metastasis development was provided. These results indicate that such multilayered analysis in a RCC animal model leads to meaningful results that are of translational significance. One Sentence Summary An aggressiveness screen with multilayer systems analysis to identify signatures and biomarkers for renal cell carcinoma aggressiveness." @default.
- W3000620706 created "2020-01-23" @default.
- W3000620706 creator A5017594953 @default.
- W3000620706 creator A5020353650 @default.
- W3000620706 creator A5030010482 @default.
- W3000620706 creator A5032686530 @default.
- W3000620706 creator A5037025946 @default.
- W3000620706 creator A5039555022 @default.
- W3000620706 creator A5040832651 @default.
- W3000620706 creator A5056955272 @default.
- W3000620706 creator A5057621269 @default.
- W3000620706 creator A5058970495 @default.
- W3000620706 creator A5063849311 @default.
- W3000620706 creator A5063987547 @default.
- W3000620706 creator A5065453835 @default.
- W3000620706 creator A5067892307 @default.
- W3000620706 creator A5068059032 @default.
- W3000620706 creator A5073536063 @default.
- W3000620706 creator A5076127920 @default.
- W3000620706 creator A5078760536 @default.
- W3000620706 creator A5079695994 @default.
- W3000620706 creator A5082775010 @default.
- W3000620706 creator A5083085617 @default.
- W3000620706 creator A5084711241 @default.
- W3000620706 creator A5087194857 @default.
- W3000620706 creator A5091460068 @default.
- W3000620706 date "2020-01-14" @default.
- W3000620706 modified "2023-10-17" @default.
- W3000620706 title "A multi-layered systems approach for renal cell carcinoma" @default.
- W3000620706 cites W1820523386 @default.
- W3000620706 cites W1821034349 @default.
- W3000620706 cites W1897772287 @default.
- W3000620706 cites W1915719235 @default.
- W3000620706 cites W1952614657 @default.
- W3000620706 cites W1967251768 @default.
- W3000620706 cites W1969057487 @default.
- W3000620706 cites W1969765652 @default.
- W3000620706 cites W1971712350 @default.
- W3000620706 cites W1971800041 @default.
- W3000620706 cites W1976043651 @default.
- W3000620706 cites W1988015039 @default.
- W3000620706 cites W1995837249 @default.
- W3000620706 cites W2000272949 @default.
- W3000620706 cites W2003723816 @default.
- W3000620706 cites W2006288875 @default.
- W3000620706 cites W2006320557 @default.
- W3000620706 cites W2012440203 @default.
- W3000620706 cites W2012976204 @default.
- W3000620706 cites W2022914202 @default.
- W3000620706 cites W2024586523 @default.
- W3000620706 cites W2026067651 @default.
- W3000620706 cites W2035618305 @default.
- W3000620706 cites W2036366189 @default.
- W3000620706 cites W2036897871 @default.
- W3000620706 cites W2045949302 @default.
- W3000620706 cites W2051138640 @default.
- W3000620706 cites W2055700074 @default.
- W3000620706 cites W2056273927 @default.
- W3000620706 cites W2065036402 @default.
- W3000620706 cites W2066469619 @default.
- W3000620706 cites W2070950435 @default.
- W3000620706 cites W2076093906 @default.
- W3000620706 cites W2079210525 @default.
- W3000620706 cites W2083887116 @default.
- W3000620706 cites W2103441770 @default.
- W3000620706 cites W2108234281 @default.
- W3000620706 cites W2108312665 @default.
- W3000620706 cites W2108871359 @default.
- W3000620706 cites W2119305519 @default.
- W3000620706 cites W2121078745 @default.
- W3000620706 cites W2128016314 @default.
- W3000620706 cites W2129407204 @default.
- W3000620706 cites W2131374955 @default.
- W3000620706 cites W2131524959 @default.
- W3000620706 cites W2137970869 @default.
- W3000620706 cites W2150194502 @default.
- W3000620706 cites W2157865341 @default.
- W3000620706 cites W2170490448 @default.
- W3000620706 cites W2257578825 @default.
- W3000620706 cites W2606675097 @default.
- W3000620706 cites W2611843839 @default.
- W3000620706 cites W2622867111 @default.
- W3000620706 cites W2726542547 @default.
- W3000620706 cites W2765188474 @default.
- W3000620706 cites W2767323531 @default.
- W3000620706 cites W2782145226 @default.
- W3000620706 cites W2782367417 @default.
- W3000620706 cites W2792937256 @default.
- W3000620706 cites W2795168220 @default.
- W3000620706 cites W2797282777 @default.
- W3000620706 cites W2797593080 @default.
- W3000620706 cites W2883968393 @default.
- W3000620706 cites W2892037279 @default.
- W3000620706 cites W2900255713 @default.
- W3000620706 cites W2902751006 @default.
- W3000620706 cites W2910652503 @default.
- W3000620706 cites W2917104728 @default.
- W3000620706 cites W2921749385 @default.
- W3000620706 cites W2968973364 @default.
- W3000620706 cites W3104123570 @default.