Identification of transaldolase as a novel serum biomarker for hepatocellular carcinoma metastasis using xenografted mouse model and clinic samples.
Hepatocellular carcinoma (HCC) is one of serious disorders with the highest morbidities and mortalities worldwide. Metastasis is the major concern that causes death in HCC. The goal of this study was to screen and identify potential serum proteins indicating HCC metastasis. Serum samples collected from control and HCCLM3-R metastatic HCC tumor model at specific stages of metastasis (1 wk, 3 wks and 6 wks) were subjected to iTRAQ labeling followed by 2DLC-ESI-MS/MS analysis. A total of 554 proteins were identified and 80 proteins were differential expressed at least between one adjacent time points. Among them, expression level of transaldolase (TALDO) was validated in mouse and human serum. The level of TALDO protein was found to be higher in metastatic mice serum compared to that of non-metastatic mice. Human specific TALDO was then identified in mouse serum through human specific peptides. Immunohistochemical and western blot analysis showed that the expression of TALDO in human HCC tissues and HCC cell lines was associated with its metastatic behavior. Subsequent screening of TALDO expression in 72 clinical serum samples (comprising 36 non-metastatic HCC and 36 metastatic HCC samples) revealed higher TALDO level in the serum of metastatic HCC patients. A receiver operating characteristic (ROC) curve estimated a maximal sensitivity of 77.8% and 86.1% specificity for TALDO in detection of HCC metastasis. The present results demonstrated that the nude mouse xenograft model is an efficient system for performing metastasis-related biomarker discovery. TALDO may be useful biomarkers for the detection of HCC metastasis.
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Cun
C
Wang
Kun
K
Guo
Dongmei
D
Gao
Xiaonan
X
Kang
Kai
K
Jiang
Yan
Y
Li
Lu
L
Sun
Shu
S
Zhang
Chun
C
Sun
Xiaohui
X
Liu
Weizhong
W
Wu
Pengyuan
P
Yang
Yinkun
Y
Liu
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011237:Predictive Value of Tests; D020543:Proteome; D012680:Sensitivity and Specificity; D044967:Serum / Q000201:enzymology; D014153:Transaldolase / Q000097:blood*; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D020543:Proteome; D014153:Transaldolase