Molecular urothelial tumor cell subtypes remain stable during metastatic evolution
Urothelial cancer (UC) care is moving toward precision oncology. For tumor biology-driven treatment of metastatic UC (mUC), molecular subtypes play a crucial role. However, it is not known whether subtypes change during metastatic evolution. To address this, we analyzed a UC progression cohort (N =...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 2024
|
| In: |
European urology
Year: 2024, Volume: 85, Issue: 4, Pages: 328-332 |
| ISSN: | 1873-7560 |
| DOI: | 10.1016/j.eururo.2023.03.020 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.eururo.2023.03.020 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0302283823026982 
|
| Author Notes: | Alexander Cox, Niklas Klümper, Johannes Stein, Danijel Sikic, Johannes Breyer, Christian Bolenz, Florian Roghmann, Philipp Erben, Ralph M. Wirtz, Bernd Wullich, Manuel Ritter, Michael Hölzel, Kristina Schwamborn, Thomas Horn, Jürgen Gschwend, Arndt Hartmann, Wilko Weichert, Franziska Erlmeier, Markus Eckstein |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1902568621 | ||
| 003 | DE-627 | ||
| 005 | 20241205172015.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240916s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.eururo.2023.03.020 |2 doi | |
| 035 | |a (DE-627)1902568621 | ||
| 035 | |a (DE-599)KXP1902568621 | ||
| 035 | |a (OCoLC)1475311651 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Cox, Alexander |e VerfasserIn |0 (DE-588)1342113551 |0 (DE-627)1902569555 |4 aut | |
| 245 | 1 | 0 | |a Molecular urothelial tumor cell subtypes remain stable during metastatic evolution |c Alexander Cox, Niklas Klümper, Johannes Stein, Danijel Sikic, Johannes Breyer, Christian Bolenz, Florian Roghmann, Philipp Erben, Ralph M. Wirtz, Bernd Wullich, Manuel Ritter, Michael Hölzel, Kristina Schwamborn, Thomas Horn, Jürgen Gschwend, Arndt Hartmann, Wilko Weichert, Franziska Erlmeier, Markus Eckstein |
| 264 | 1 | |c April 2024 | |
| 300 | |b Illustrationen | ||
| 300 | |a 5 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online verfügbar: 6. April 2023, Artikelversion: 12. März 2024 | ||
| 500 | |a Gesehen am 16.09.2024 | ||
| 520 | |a Urothelial cancer (UC) care is moving toward precision oncology. For tumor biology-driven treatment of metastatic UC (mUC), molecular subtypes play a crucial role. However, it is not known whether subtypes change during metastatic evolution. To address this, we analyzed a UC progression cohort (N = 154 patients) with 138 matched primary tumors (PRIM) and synchronous or metachronous distant metastasis (MET) by immunohistochemistry, and mRNA sequencing in a subgroup of 20 matched pairs. Protein-based tumor cell subtypes and histomorphology remained stable during metastatic progression (concordance: 94%, 95% confidence interval [CI] 88-97%). In comparison, transcriptome-based molecular consensus subtypes exhibited higher heterogeneity between PRIM and MET (concordance: 45%, 95% CI 23-69%), with switches particularly occurring between luminal and stroma-rich tumors. Of note, all tumors classified as stroma rich showed luminal tumor cell differentiation. By an in-depth analysis, we found a negative correlation of luminal gene and protein expression with increasing desmoplastic stroma content, suggesting that luminal tumor cell differentiation of “stroma-rich tumors” is superimposed by gene expression signals stemming from the stromal compartment. Immunohistochemistry allows tumor cell subtyping into luminal, basal, or neuroendocrine classes that remain stable during metastatic progression. These findings expand our biological understanding of UC MET and have implications for future subtype-stratified clinical trials in patients with mUC. - Patient summary - Urothelial carcinomas (UCs) occur in different appearances, the so-called molecular subtypes. These molecular subtypes will gain importance for the therapy of metastatic UCs in the future. We could demonstrate that the subtype remains stable during metastasis, which is highly relevant for future studies. | ||
| 650 | 4 | |a Metastatic evolution | |
| 650 | 4 | |a Metastatic urothelial carcinoma | |
| 650 | 4 | |a Molecular subtypes | |
| 650 | 4 | |a Subtypes | |
| 650 | 4 | |a Urothelial cancer | |
| 700 | 1 | |a Klümper, Niklas |e VerfasserIn |0 (DE-588)1293974110 |0 (DE-627)185095772X |4 aut | |
| 700 | 1 | |a Stein, Johannes |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sikic, Danijel |d 1982- |e VerfasserIn |0 (DE-588)141368551 |0 (DE-627)627282350 |0 (DE-576)323536646 |4 aut | |
| 700 | 1 | |a Breyer, Johannes |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bolenz, Christian |d 1976- |e VerfasserIn |0 (DE-588)133152707 |0 (DE-627)537509852 |0 (DE-576)29965754X |4 aut | |
| 700 | 1 | |a Roghmann, Florian Bernhard Gerhard |d 1980- |e VerfasserIn |0 (DE-588)140688145 |0 (DE-627)620888156 |0 (DE-576)319420485 |4 aut | |
| 700 | 1 | |a Erben, Philipp |d 1973- |e VerfasserIn |0 (DE-588)128501014 |0 (DE-627)373920997 |0 (DE-576)297181661 |4 aut | |
| 700 | 1 | |a Wirtz, Ralph M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wullich, Bernd |d 1960- |e VerfasserIn |0 (DE-588)110835794 |0 (DE-627)691096716 |0 (DE-576)302885749 |4 aut | |
| 700 | 1 | |a Ritter, Manuel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hölzel, Michael |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schwamborn, Kristina |d 1976- |e VerfasserIn |0 (DE-588)13043745X |0 (DE-627)501474439 |0 (DE-576)29819547X |4 aut | |
| 700 | 1 | |a Horn, Thomas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gschwend, Jürgen E. |d 1962- |e VerfasserIn |0 (DE-588)111741300 |0 (DE-627)523317697 |0 (DE-576)178294446 |4 aut | |
| 700 | 1 | |a Hartmann, Arndt |e VerfasserIn |4 aut | |
| 700 | 1 | |a Weichert, Wilko |d 1970-2023 |e VerfasserIn |0 (DE-588)123509106 |0 (DE-627)56134650X |0 (DE-576)293740461 |4 aut | |
| 700 | 1 | |a Erlmeier, Franziska |d 1985- |e VerfasserIn |0 (DE-588)107067804X |0 (DE-627)824446550 |0 (DE-576)432206434 |4 aut | |
| 700 | 1 | |a Eckstein, Markus |d 1990- |e VerfasserIn |0 (DE-588)1113210656 |0 (DE-627)867126388 |0 (DE-576)476917069 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European urology |d Amsterdam [u.a.] : Elsevier Science, 1976 |g 85(2024), 4 vom: Apr., Seite 328-332 |h Online-Ressource |w (DE-627)300191596 |w (DE-600)1482253-2 |w (DE-576)099718103 |x 1873-7560 |7 nnas |a Molecular urothelial tumor cell subtypes remain stable during metastatic evolution |
| 773 | 1 | 8 | |g volume:85 |g year:2024 |g number:4 |g month:04 |g pages:328-332 |g extent:5 |a Molecular urothelial tumor cell subtypes remain stable during metastatic evolution |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.eururo.2023.03.020 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S0302283823026982 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20240916 | ||
| 993 | |a Article | ||
| 994 | |a 2024 | ||
| 998 | |g 128501014 |a Erben, Philipp |m 128501014:Erben, Philipp |d 60000 |d 63100 |e 60000PE128501014 |e 63100PE128501014 |k 0/60000/ |k 1/60000/63100/ |p 8 | ||
| 999 | |a KXP-PPN1902568621 |e 4580215877 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"type":{"media":"Online-Ressource","bibl":"article-journal"},"origin":[{"dateIssuedKey":"2024","dateIssuedDisp":"April 2024"}],"language":["eng"],"relHost":[{"recId":"300191596","pubHistory":["Nachgewiesen 2.1976 -"],"disp":"Molecular urothelial tumor cell subtypes remain stable during metastatic evolutionEuropean urology","note":["Ungezählte Beil. bis 40.2001: Supplement"],"id":{"eki":["300191596"],"zdb":["1482253-2"],"issn":["1873-7560","1421-993X"]},"title":[{"subtitle":"official organ of the European Association of Urology, the European Organization for Research and Treatment of Cancer - Genito-Urinary Group, the European Society for Urological Oncology and Endocrinology","title":"European urology","title_sort":"European urology"}],"origin":[{"publisher":"Elsevier Science ; Karger","dateIssuedKey":"1976","publisherPlace":"Amsterdam [u.a.] ; Basel","dateIssuedDisp":"1976-"}],"type":{"media":"Online-Ressource","bibl":"periodical"},"language":["eng"],"physDesc":[{"extent":"Online-Ressource"}],"part":{"pages":"328-332","extent":"5","year":"2024","volume":"85","issue":"4","text":"85(2024), 4 vom: Apr., Seite 328-332"}}],"physDesc":[{"noteIll":"Illustrationen","extent":"5 S."}],"person":[{"family":"Cox","roleDisplay":"VerfasserIn","role":"aut","display":"Cox, Alexander","given":"Alexander"},{"roleDisplay":"VerfasserIn","family":"Klümper","given":"Niklas","role":"aut","display":"Klümper, Niklas"},{"role":"aut","display":"Stein, Johannes","given":"Johannes","roleDisplay":"VerfasserIn","family":"Stein"},{"given":"Danijel","display":"Sikic, Danijel","role":"aut","roleDisplay":"VerfasserIn","family":"Sikic"},{"roleDisplay":"VerfasserIn","family":"Breyer","given":"Johannes","role":"aut","display":"Breyer, Johannes"},{"roleDisplay":"VerfasserIn","family":"Bolenz","role":"aut","display":"Bolenz, Christian","given":"Christian"},{"family":"Roghmann","roleDisplay":"VerfasserIn","given":"Florian Bernhard Gerhard","display":"Roghmann, Florian Bernhard Gerhard","role":"aut"},{"roleDisplay":"VerfasserIn","family":"Erben","given":"Philipp","display":"Erben, Philipp","role":"aut"},{"family":"Wirtz","roleDisplay":"VerfasserIn","given":"Ralph M.","display":"Wirtz, Ralph M.","role":"aut"},{"family":"Wullich","roleDisplay":"VerfasserIn","given":"Bernd","role":"aut","display":"Wullich, Bernd"},{"display":"Ritter, Manuel","role":"aut","given":"Manuel","family":"Ritter","roleDisplay":"VerfasserIn"},{"given":"Michael","display":"Hölzel, Michael","role":"aut","family":"Hölzel","roleDisplay":"VerfasserIn"},{"family":"Schwamborn","roleDisplay":"VerfasserIn","display":"Schwamborn, Kristina","role":"aut","given":"Kristina"},{"family":"Horn","roleDisplay":"VerfasserIn","role":"aut","display":"Horn, Thomas","given":"Thomas"},{"display":"Gschwend, Jürgen E.","role":"aut","given":"Jürgen E.","family":"Gschwend","roleDisplay":"VerfasserIn"},{"display":"Hartmann, Arndt","role":"aut","given":"Arndt","roleDisplay":"VerfasserIn","family":"Hartmann"},{"roleDisplay":"VerfasserIn","family":"Weichert","given":"Wilko","display":"Weichert, Wilko","role":"aut"},{"roleDisplay":"VerfasserIn","family":"Erlmeier","role":"aut","display":"Erlmeier, Franziska","given":"Franziska"},{"roleDisplay":"VerfasserIn","family":"Eckstein","role":"aut","display":"Eckstein, Markus","given":"Markus"}],"name":{"displayForm":["Alexander Cox, Niklas Klümper, Johannes Stein, Danijel Sikic, Johannes Breyer, Christian Bolenz, Florian Roghmann, Philipp Erben, Ralph M. Wirtz, Bernd Wullich, Manuel Ritter, Michael Hölzel, Kristina Schwamborn, Thomas Horn, Jürgen Gschwend, Arndt Hartmann, Wilko Weichert, Franziska Erlmeier, Markus Eckstein"]},"note":["Online verfügbar: 6. April 2023, Artikelversion: 12. März 2024","Gesehen am 16.09.2024"],"recId":"1902568621","id":{"doi":["10.1016/j.eururo.2023.03.020"],"eki":["1902568621"]},"title":[{"title":"Molecular urothelial tumor cell subtypes remain stable during metastatic evolution","title_sort":"Molecular urothelial tumor cell subtypes remain stable during metastatic evolution"}]} | ||
| SRT | |a COXALEXANDMOLECULARU2024 | ||