Abstract
Purpose
The aim of this study was to investigate the roles of renal tumor antigen (RAGE) in the progression and clinical outcome of hepatocellular carcinoma (HCC).
Methods
RAGE mRNA levels in 350 cases of HCC were investigated by quantitative real-time reverse transcription polymerase chain reaction. We analyzed the relationship of RAGE mRNA level with clinicopathologic parameters and clinical outcome. To identify the possible role of RAGE on cellular invasion, we performed in vitro analyses using small interfering RNAs (siRNAs).
Results
RAGE mRNA level was significantly higher in HCC than in noncancerous hepatic tissues (P < 0.001). Overexpression of RAGE was significantly correlated with the presence of multiple tumors (P = 0.021), high alfa-fetoprotein level (P = 0.042), and advanced tumor stage (P = 0.016). Higher levels of RAGE expression were associated with significantly shorter overall survival time (P = 0.029). Knockdown of RAGE expression by siRNAs suppressed the invasive ability of HCC cells and the expression and secretion of matrix metalloproteinase-9 (MMP-9). We found that RAGE and MMP-9 expressions were correlated in HCCs, and furthermore, the combination of RAGE and MMP-9 expression was associated with the survival of patients (P = 0.0066).
Conclusions
Our results suggest that RAGE may be important in tumor invasion and could be a potential predictor for the prognosis of HCC patients.
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Acknowledgment
This research was financially supported by the Ministry of Education, Science and Technology and Korea Institute for Advancement of Technology through the Human Resource Training Project for Regional Innovation and by grant 10024733 of the Ministry of Knowledge and Economy of Korea. We thank Dr. D.-G. Kim for providing SH-J1 cells.
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Cha, H.J., Kim, J., Hong, S.M. et al. Overexpression of Renal Tumor Antigen Is Associated with Tumor Invasion and Poor Prognosis of Hepatocellular Carcinoma. Ann Surg Oncol 19 (Suppl 3), 404–411 (2012). https://doi.org/10.1245/s10434-011-1856-3
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DOI: https://doi.org/10.1245/s10434-011-1856-3