A Comprehensive Investigation toward the Indicative Proteins of Bladder Cancer in Urine: From Surveying Cell Secretomes to Verifying Urine Proteins.
Urine is an ideal material to study the cancer-related protein biomarkers in bladder, whereas exploration to these candidates is confronting technique challenges. Herein, we propose a comprehensive strategy of searching the urine proteins related with bladder cancer. The strategy consists of three core combinations, screening the biomarker candidates in the secreted proteins derived from the bladder cancer cell lines and verifying them in patient urines, defining the differential proteins through two-dimensional electrophoresis (2DE) and isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS, and implementing quantitative proteomics of profiling and targeting analysis. With proteomic survey, a total of 700 proteins were found with their abundance of secreted proteins in cancer cell lines different from normal, while 87 proteins were identified in the urine samples. The multiple reaction monitoring (MRM)-based quantification was adapted in verifying the bladder cancer related proteins in individual urine samples, resulting in 10 differential urine proteins linked with the cancer. Of these candidates, receiver operating characteristic analysis revealed that the combination of CO3 and LDHB was more sensitive as the cancer indicator than other groups. The discovery of the bladder cancer indicators through our strategy has paved an avenue to further biomarker validation.
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing, 100101, China.|University of Chinese Academy of Sciences , Beijing, 100049, China.
Jiao
J
Guo
Proteomics Division, BGI-Shenzhen , Shenzhen, Guangdong 518083, China.
Yan
Y
Ren
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing, 100101, China.|University of Chinese Academy of Sciences , Beijing, 100049, China.
Guixue
G
Hou
Proteomics Division, BGI-Shenzhen , Shenzhen, Guangdong 518083, China.
Bo
B
Wen
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing, 100101, China.|University of Chinese Academy of Sciences , Beijing, 100049, China.
Feng
F
Xian
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing, 100101, China.
Zhen
Z
Chen
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing, 100101, China.
Ping
P
Cui
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing, 100101, China.|University of Chinese Academy of Sciences , Beijing, 100049, China.
Yingying
Y
Xie
Proteomics Division, BGI-Shenzhen , Shenzhen, Guangdong 518083, China.
Jin
J
Zi
Proteomics Division, BGI-Shenzhen , Shenzhen, Guangdong 518083, China.
Liang
L
Lin
Shenzhen Second People's Hospital , Shenzhen, Guangdong 518028, China.
Song
S
Wu
Shenzhen Second People's Hospital , Shenzhen, Guangdong 518028, China.
Zesong
Z
Li
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing, 100101, China.|University of Chinese Academy of Sciences , Beijing, 100049, China.
Lin
L
Wu
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing, 100101, China.|University of Chinese Academy of Sciences , Beijing, 100049, China.
Xiaomin
X
Lou
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing, 100101, China.|University of Chinese Academy of Sciences , Beijing, 100049, China.|Proteomics Division, BGI-Shenzhen , Shenzhen, Guangdong 518083, China.
Siqi
S
Liu
D014408:Biomarkers, Tumor / Q000652:urine*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism / Q000652:urine*; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D053719:Tandem Mass Spectrometry; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
2DE; MRM; biomarker; bladder cancer; iTRAQ; urine