Mitochondrial heat shock protein 75 (MTHSP75) is a predictive marker for early tumor recurrence in hepatocellular carcinoma

Abstract

Background & Aims: Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide. Although surgical treatment has been considered the most effective option, the prognosis of HCC after surgery remains unsatisfactory and survival rate is still very poor. It is because HCC is often diagnosed at advanced stages with a high tumor recurrence rate. Reliable biomarkers to identify patients who are at high-risk for early recurrence would be beneficial for better post-operative management of this malignancy. Patients & Methods: In this study, we collected 55 HCC frozen tissues from patients with tumor recurrence (n 20) or surviving disease-free (n 35) during one-year post-operative follow up. HCC tissues were subjected to 2-DE gel electrophoresis (pI 4-7; 22cm strip) and proteomic expression profiling was analyzed by PDQuest software and ANN/CART data-mining algorithms. An area of relative operating characteristic (ROC) curves 0.70 was considered to be significant between the recurrence and disease-free groups. Correlations of predictive biomarkers with clinicopathological data such as tumor stage, tumor size, microsatallite and venous infiltration were also investigated. Biomarkers of predictive values were unequivocally identified by tandem mass spectrometer. Real-time PCR, Western blot and immunohistochemistry were used for biomarker validation. Results: A total of 1433 protein spots were identified in the HCC proteome. Among the 90 dysregulated protein species between the tumorous and non-cancerous liver tissues, mitochondrial heat shock protein 75 (MTHSP75) was over-expressed in HCC and significantly correlated with early tumor recurrence (AUC 0.83). Further validation test revealed that MTHSP75 has a sensitivity of 90.5% and a specificity of 72.7% for 1-year tumor recurrence in HCC. Besides, MTHSP75 was also found in significant association with tumor TNM stage (r 0.303, p 0.01). Conclusion: The present finding demonstrated the over-expression of MTHSP75 protein in primary HCC tissues, which may be used as a predictive biomarker for HCC patients with early tumor recurrence after surgery. For this at-risk group of HCC, post-operative monitoring of disease relapse and additional therapies may be necessary before the appearance of tumor recurrence.