title: Identification of predictors of patient survival with TSPAN8 as a mediator of tumor aggressiveness in clear cell renal cell carcinoma
creator: Geist, Felix
subject: ddc-500
subject: 500 Natural sciences and mathematics
subject: ddc-570
subject: 570 Life sciences
subject: ddc-600
subject: 600 Technology (Applied sciences)
subject: ddc-610
subject: 610 Medical sciences Medicine
description: With the help of a patient-derived clear cell renal cell carcinoma (ccRCC) model system previously established in our laboratory, which recapitulates the heterogeneity of the originating tumor, we were able to study ccRCC on a functional level. In five rounds and in four biological replicates of an in vivo selection, we transplanted lung metastases of orthotopically transplanted tumor cells into the renal capsules of NOD scid gamma (NSG) mice. The tumor was enriched for cells with increased growth and higher metastatic potential compared to the initial heterogeneous population. Comparative gene expression analysis revealed candidate genes associated with enhanced malignant growth and metastasis. Least absolute shrinkage and selection operator (LASSO) regression identified a gene signature that can robustly predict cancer specific patient survival. The prognostic power of our signature was additionally verified in independent patient cohorts suggesting that this approach leverages efficient stratification of patients into distinctive risk groups. Intra- and intertumor heterogeneity remains a clinical challenge as estimated survival rates could vary substantially when comparing different tumor regions.  Tetraspanin-8 (TSPAN8) was identified as one of the hallmark genes in the generated ccRCC signature and is known to alter cellular signaling. Therefore, we hypothesized that TSPAN8 contributes to tumor aggressiveness and thus to growth and metastasis of ccRCC. In fact, in knockdown and overexpression xenografts experiments, we could confirm an essential role for tumor aggressiveness in vivo suggesting that TSPAN8 is an attractive target for treatment of clear cell renal cell carcinoma.
date: 2020
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/26564/1/Thesis%20print7.pdf
identifier: DOI:10.11588/heidok.00026564
identifier: urn:nbn:de:bsz:16-heidok-265645
identifier:   Geist, Felix  (2020) Identification of predictors of patient survival with TSPAN8 as a mediator of tumor aggressiveness in clear cell renal cell carcinoma.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/26564/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng