Identification of novel serological tumor markers for human prostate cancer using integrative transcriptome and proteome analysis.
The aim of this study was to identify novel serological tumor markers for human prostate cancer (PCa). We compared the gene expression profile of PCa tissues to adjacent benign tissues of prostate using gene expression microarray. 1207 genes that were consistently different from adjacent benign tissues of prostate (paired t test, P<0.05) were selected as differentially expressed genes (DEGs). Among them, 652 DEGs were upregulated in PCa, whereas 555 DEGs were downregulated in PCa. In addition, two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with MS was performed to screen for candidate markers in the proteome of PCa and adjacent benign tissues of prostate. A total of 89 spots were significantly up-regulated (ratio≥2, P<0.01) in PCa samples, whereas 66 spots were down-regulated (ratio≤-2, P<0.01). Sixty gene products were identified among these spots. Moreover, 14 potential candidate markers, which were identified as differentially expressed molecules by both gene expression microarray and 2D-DIGE, were chosen for validation and analysis by ELISA. The serum levels of three proteins correlated well with the 2D-DIGE results. Furthermore, the increased serum level of Inosine monophosphate dehydrogenase II (IMPDH2) was significantly associated with the clinicopathological features of the patients with PCa, suggesting its potential as a serological tumor marker. These results demonstrated that integrative transcriptome and proteome analysis could be a powerful tool for marker discovery in PCa. We suggest IMPDH2 as a novel serological tumor marker for detection of early PCa and evaluation of tumor progression.
Department of Urology, Guangzhou First Municipal People's Hospital, Affiliated Guangzhou Medical College, Guangzhou, 510180, China.
Zhao-dong
ZD
Han
Yan-qiong
YQ
Zhang
Hui-chan
HC
He
Qi-shan
QS
Dai
Guo-qiang
GQ
Qin
Jia-hong
JH
Chen
Chao
C
Cai
Xin
X
Fu
Xue-cheng
XC
Bi
Jian-guo
JG
Zhu
Dong-jiang
DJ
Liao
Xin-peng
XP
Lu
Zi-yao
ZY
Mo
Yun-ping
YP
Zhu
Wei-de
WD
Zhong
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D019735:Carbon-Carbon Ligases / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D018841:HSP90 Heat-Shock Proteins / Q000097:blood*; D006801:Humans; D007168:IMP Dehydrogenase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D040901:Proteomics; D059467:Transcriptome; D057825:Two-Dimensional Difference Gel Electrophoresis
D014408:Biomarkers, Tumor; D018841:HSP90 Heat-Shock Proteins; D009363:Neoplasm Proteins; C092306:TRAP1 protein, human; D007168:IMP Dehydrogenase; C501687:IMPDH2 protein, human; D019735:Carbon-Carbon Ligases; C021573:methylcrotonoyl-CoA carboxylase