Validation and clinicopathologic associations of a urine-based bladder cancer biomarker signature.
BACKGROUND
To validate the expression of a urine-based bladder cancer associated diagnostic signature comprised of 10 targets; ANG, CA9, MMP9, MMP10, SERPINA1, APOE, SDC1, VEGFA, SERPINE1 and IL8 in bladder tumor tissues.


METHODS
Immunohistochemical analyses were performed on tumor specimens from 213 bladder cancer patients (transitional cell carcinoma only) and 74 controls. Staining patterns were digitally captured and quantitated (Aperio, Vista, CA), and expression was correlated with tumor stage, tumor grade and outcome measures.


RESULTS
We revealed a positive association of 9 of the 10 proteins (excluding VEGF) in bladder cancer. Relative to control cases, a reduction in SDC1 and overexpression of MMP9, MMP10, SERPINE1, IL8, APOE, SERPINA1, ANG were associated with high stage bladder cancer. Reduced VEGF and increased SERPINA1 were associated with high-grade bladder cancer. Disease-specific survival was significantly reduced in tumors with high expression of SERPINE1 and/or IL8.


CONCLUSIONS
These findings confirm that the proteins in a urine-based diagnostic signature are aberrantly expressed in bladder tumor tissues, and support the potential additional utility of selected biomarkers for the clinicopathological evaluation of excised tissue or biopsy material.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_200.
MD Anderson Cancer Center Orlando, Cancer Research Institute, Orlando, Florida, USA. zge123@yahoo.com.
Ge
G
Zhang
MD Anderson Cancer Center Orlando, Cancer Research Institute, Orlando, Florida, USA. evangomes24@gmail.com.
Evan
E
Gomes-Giacoia
Department of Biostatistics, The University of Florida, Gainesville, Florida, USA. ydai@ichp.ufl.edu.
Yunfeng
Y
Dai
Department of Pathology, Orlando Health, Orlando, FL, USA. adriennelawton@gmail.com.
Adrienne
A
Lawton
MD Anderson Cancer Center Orlando, Cancer Research Institute, Orlando, Florida, USA. makitomiyake@yahoo.co.jp.
Makito
M
Miyake
University of Hawaii Cancer Center, 701 Ilalo St, Rm 327, Honolulu, HI, 96813, USA. hfuruya@cc.hawaii.edu.
Hideki
H
Furuya
MD Anderson Cancer Center Orlando, Cancer Research Institute, Orlando, Florida, USA. goodisonsteve@gmail.com.|Nonagen Bioscience Corp, Orlando, Florida, USA. goodisonsteve@gmail.com.|Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, USA. goodisonsteve@gmail.com.
Steve
S
Goodison
MD Anderson Cancer Center Orlando, Cancer Research Institute, Orlando, Florida, USA. crosser@cc.hawaii.edu.|Nonagen Bioscience Corp, Orlando, Florida, USA. crosser@cc.hawaii.edu.|University of Hawaii Cancer Center, 701 Ilalo St, Rm 327, Honolulu, HI, 96813, USA. crosser@cc.hawaii.edu.
Charles J
CJ
Rosser
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000652:urine; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery / Q000652:urine
D014408:Biomarkers, Tumor