Proteome Profiling of Urinary Exosomes Identifies Alpha 1-Antitrypsin and H2B1K as Diagnostic and Prognostic Biomarkers for Urothelial Carcinoma.
MALDI-TOF spectrometry has not been used for urinary exosome analysis. We used it for determining UC biomarkers. From 2012 to 2015, we enrolled 129 consecutive patients with UC and 62 participants without UC. Exosomes from their urine were isolated, and analyzed through MALDI-TOF spectrometry. Immunohistochemical (IHC) analysis of another 122 UC and 26 non-UC tissues was conducted to verify the discovered biomarkers. Two peaks at m/z 5593 (fragmented peptide of alpha-1-antitrypsin; sensitivity, 50.4%; specificity, 96.9%) and m/z 5947 (fragmented peptide of histone H2B1K sensitivity, 62.0%; specificity, 92.3%) were identified as UC diagnosis exosome biomarkers. UC patients with detectable histone H2B1K showed 2.29- and 3.11-fold increased risks of recurrence and progression, respectively, compared with those with nondetectable histone H2B1K. Verification results of IHC staining revealed significantly higher expression of alpha 1-antitrypsin (p = 0.038) and H2B1K (p = 0.005) in UC tissues than in normal tissues. The expression of alpha 1-antitrypsin and H2B1K in UC tissues was significantly correlated with UC grades (p < 0.05). Urinary exosome proteins alpha 1-antitrypsin and histone H2B1K, which are identified through MALDI-TOF analysis, could facilitate rapid diagnosis and prognosis of UC.
Institute of Clinical Medical Science, China Medical University College of Medicine, Taichung, Taiwan.|Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.|Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan.
Shih-Yi
SY
Lin
Department of Urology, China Medical University Hospital, Taichung, Taiwan.
Chao-Hsiang
CH
Chang
Department of Urology, China Medical University Hospital, Taichung, Taiwan.
His-Chin
HC
Wu
Institute of Clinical Medical Science, China Medical University College of Medicine, Taichung, Taiwan.|Department of Hematology and Oncology, China Medical University Hospital, Taichung, Taiwan.
Ching-Chan
CC
Lin
Department of Pathology, China Medical University Hospital, Taichung, Taiwan.
Kai-Po
KP
Chang
Department of Urology, China Medical University Hospital, Taichung, Taiwan.
Chi-Rei
CR
Yang
Institute of Clinical Medical Science, China Medical University College of Medicine, Taichung, Taiwan.|Department of Urology, China Medical University Hospital, Taichung, Taiwan.
Chi-Ping
CP
Huang
Institute of Clinical Medical Science, China Medical University College of Medicine, Taichung, Taiwan.|Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.|Department of Chest Medicine, China Medical University Hospital, Taichung, Taiwan.
Wu-Huei
WH
Hsu
Institute of Clinical Medical Science, China Medical University College of Medicine, Taichung, Taiwan.|Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.|Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan.
Chiz-Tzung
CT
Chang
Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.|Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
Chao-Jung
CJ
Chen
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