Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma

Neil Shimwell, Richard Bryan, Wenbin Wei, Nicholas James, Kar Cheng, Maurice Zeegers, Philip Johnson, Ashley Martin, Douglas Ward

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)
35 Downloads (Pure)



Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic analysis of cancer cell line secretomes as a strategy to discover urinary biomarkers for bladder cancer.


We used shotgun proteomics to identify proteins secreted by three bladder cancer cell lines. Secreted proteins with high mRNA levels in bladder tumours relative to normal urothelium were assayed by ELISA in urine samples from 642 patients.


Midkine and HAI-1 were significantly increased in bladder cancer patients, with the highest levels in invasive disease (area under the receiver operating characteristic curve 0.89 vs non-cancer). The urinary concentration of both proteins was too high to be explained by bladder cancer associated haematuria and most likely arises by direct tumour secretion.


This ‘dual-omic’ strategy identified tumour secreted proteins whose urine concentrations are increased significantly by bladder cancer. Combined secretome-transcriptome analysis may be more useful than direct proteomic analysis of body fluids for biomarker discovery in both bladder cancer and other tumour types.
Original languageEnglish
Pages (from-to)1854-1861
Number of pages8
JournalBritish Journal of Cancer
Issue number9
Early online date16 Apr 2013
Publication statusPublished - 14 May 2013

Bibliographical note

Publication date on PubMed is shown as 14th May 2013.


  • urine
  • secretome
  • biomarker
  • bladder cancer
  • midkine


Dive into the research topics of 'Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma'. Together they form a unique fingerprint.
  • Bladder cancer prognosis

    Bryan, R. & Ward, D., 2 Jun 2016, IPC No. G01N 33/574 (2006.01), G01N 33/68 (2006.01), Patent No. WO/2016/083832, Priority date 28 Nov 2014, Priority No. US 62/085,433

    Research output: Patent

    Open Access

Cite this