Glucose-regulated protein 78 regulates the expression of mitochondrial genesis proteins in HBV-related hepatocellular carcinoma: a clinical analysis

Objective To investigate the expression of glucose-regulated protein 78 ( GRP78) in HBV-related hepatocellular carcinoma ( HBV-HCC) and its association with clinicopathological features, as well as its regulatory effect on mitochondrial genesis proteins in hepatoma cells, and to provide a basis for new strategies for the prevention and treatment of HCC. Methods Tissue samples were collected from54 patients with HBV-HCC, and immunohistochemistry and Western blot were used to measure the expression of GRP78, Lon, TFAM, and cytochrome C oxidase Ⅳ ( COX Ⅳ) . The expression of GRP78 in hepatoma cells was interfered by siRNA, and then the expression of GRP78, Lon, mitochondrial transcription factor A ( TFAM) , and COX Ⅳ was measured. Quantitative real-time PCR was used to measure the level of mitochondrial DNA ( mt DNA) in clinical specimens and HCC cells after GRP78 expression was interfered with. A statistical analysis was performed for clinical and experimental data. The t-test was used for comparison of continuous data between groups, the Fisher's exact test was used for comparison of categorical data between groups, and the Kaplan-Meier method was used for survival analysis. Results Compared with the adjacent tissues, HBV-HCC tissues had significantly higher expression of GRP78 and Lon ( t = 9. 135 and 5. 523, both P < 0. 0001) and significantly lower expression of the mitochondrial genesis proteins TFAM and COX Ⅳ and mt DNA level ( t = 2. 765, 4. 260, and 12. 280, P = 0. 011, < 0. 001, and < 0. 001) . There were significant increases in the expression of the mitochondrial genesis proteins TFAM and COX Ⅳ and mt DNA level after the interference with GRP78 expression in hepatoma cells ( all P < 0. 05) . There were significant differences in the expression of GRP78 between patients with different numbers of tumors, patients with and without portal vein tumor thrombus, and patients with different tumor stages ( P = 0. 016, 0. 003, and 0. 045) . The patients with low GRP78 expression had significantly longer overall survival and recurrence-free survival after surgery than those with high GRP78 expression ( χ2= 5. 006 and4. 995, P = 0. 025 and 0. 026) . Conclusion GRP78 has a potential regulatory effect on mitochondrial genesis and maintenance and has important clinical guiding significance in establishing new strategies for the prevention and treatment of HCC.