Proteomics

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Proteomic Analysis of the Urothelial Cancer Landscape


ABSTRACT: Urothelial cancer is a challenging disease with a wide tumor-biological spec-trum. Most molecular classification attempts are transcriptome-based and re-late only indirectly to the therapeutically relevant protein level. We improve preanalytical preparation of clinical samples for proteome analyses and char-acterize a comprehensive cohort of 434 samples with 242 tumors and 192 paired normal mucosae. We evaluate sample-wise tumor specificity and rank biomarkers by target relevance. We identify five tumor clusters that add prog-nostic information independent from histopathological groups. In silico drug prediction suggests efficacy of several compounds hitherto not in clinical use. Both, in silico as well as in vitro data, indicate predictive value of the proteo-mic clusters for these drugs. Comparative validation on external transcriptom-ic data confirms prognostic relevance and contextualizes proteomic and tran-scriptomic classifications. A real-world diagnostic approach based on im-munohistochemistry further validates our proteomic data but underlines the necessity of omics scale molecular analyses for personalized oncology.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Solid Cancer Cell

SUBMITTER: Hannah Voß  

LAB HEAD: Franz F. Dressler

PROVIDER: PXD041733 | Pride | 2024-06-16

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
210630_CK_FFD_10D.raw Raw
210630_CK_FFD_11D.raw Raw
210630_CK_FFD_12D.raw Raw
210630_CK_FFD_13D.raw Raw
210630_CK_FFD_14D.raw Raw
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Publications


Urothelial bladder cancer (UC) has a wide tumor biological spectrum with challenging prognostic stratification and relevant therapy-associated morbidity. Most molecular classifications relate only indirectly to the therapeutically relevant protein level. We improve the pre-analytics of clinical samples for proteome analyses and characterize a cohort of 434 samples with 242 tumors and 192 paired normal mucosae covering the full range of UC. We evaluate sample-wise tumor specificity and rank bioma  ...[more]

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