Combined use of epithelial membrane antigen and nuclear matrix protein 52 as sensitive biomarkers for detection of bladder cancer.
BACKGROUND
The advent of noninvasive urine-based markers as well as other novel modalities has yielded improved diagnostic accuracy. However, the new markers failed to reach higher sensitivity and specificity. We therefore evaluated the potential role of epithelial membrane antigen (EMA) and nuclear matrix protein 52 (NMP-52) singly and combined as noninvasive biomarkers for the detection of bladder cancer (BC).


METHODS
A total of 160 individuals including 66 patients with BC, 54 patients with benign urologic disorders and 40 healthy volunteers were investigated. Urinary EMA at 130 kDa and NMP at 52 kDa were identified, purified and quantified by Western blot, electroelution and enzyme-linked immunosorbent assay (ELISA). The diagnostic performance of each biomarker and their combination were compared using area under receiver operating characteristic curves (AUC).


RESULTS
Mean urinary EMA, 2.42 µg/mL, and NMP-52, 17.85 µg/mL, were significantly elevated in patients with BC compared to controls, 1.18 and 3.44 µg/mL, respectively (p&lt;0.0001). The combined use of these markers yielded values which were increased 4.4- and 13.7-fold in the benign and malignant disease groups, respectively, with respect to the normal group. The values of EMA and NMP-52 were significantly higher in patients with higher-grade tumors than those with lower-grade tumors (p&lt;0.0001). Moreover, this combination could predict all BC stages and grades with 0.91 AUC, 94% sensitivity and 80% specificity.


CONCLUSIONS
EMA and NMP-52 in combination could be promising noninvasive biomarkers for BC detection.
Research and Development Department, Biotechnology Research Center, New Damietta City - Egypt.
Abdelfattah M
AM
Attallah
Chemistry Department, Faculty of Science, Mansoura University, Mansoura - Egypt.
Mohamed
M
El-Far
Chemistry Department, Faculty of Science, Cairo University, Giza - Egypt.
Sanaa O
SO
Abdallah
Chemistry Department, Faculty of Science, Mansoura University, Mansoura - Egypt.
Ahmed M
AM
El-Waseef
Chemistry Department, Faculty of Science, Helwan University, Cairo - Egypt.
Mohamed M
MM
Omran
Research and Development Department, Biotechnology Research Center, New Damietta City - Egypt.
Mohamed A
MA
Abdelrazek
Research and Development Department, Biotechnology Research Center, New Damietta City - Egypt.
Ahmed A
AA
Attallah
Research and Development Department, Biotechnology Research Center, New Damietta City - Egypt.
Mohamed J
MJ
Saadh
Research and Development Department, Biotechnology Research Center, New Damietta City - Egypt.
Mohamed
M
Radwan
Research and Development Department, Biotechnology Research Center, New Damietta City - Egypt.
Kholoud A
KA
El-waffaey
Department of Urology, Urology-Nephrology Center, Mansoura University, Mansoura - Egypt.
Hassan
H
Abol-Enei
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000652:urine; D016022:Case-Control Studies; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000652:urine*; D018307:Neoplasms, Squamous Cell / Q000175:diagnosis* / Q000652:urine; D034521:Nuclear Matrix-Associated Proteins / Q000652:urine*; D011446:Prospective Studies; D012372:ROC Curve; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine
D014408:Biomarkers, Tumor; D018396:Mucin-1; D034521:Nuclear Matrix-Associated Proteins; C000610443:nuclear matrix protein 52, human