Ratio Of Tumor To Peritumoral Mitochondrial Dna Content Predicts Prognosis Of Hepatitis B Virus-Related Hepatocellular Carcinoma

Mitochondrial DNA (mtDNA) content alteration is reported to play important roles in tumorigenesis and tumor progression. However, few studies have focused on the peritumoral tissues mtDNA copy number. In this study, we evaluated the relationship between tumor/peritumoral tissues mtDNA content and the 5-year recurrence risk of hepatocellular carcinoma (HCC). A total of 124 HBV-infected patients who had undergone curative resection for HCC were retrospectively analyzed. The mtDNA content in tumor and peritumoral tissues were determined by quantitative realtime PCR. Intratumoral mtDNA content was significantly lower than that in peritumoral tissues (P = 0.027). Compared to individuals with high mtDNA content in peritumor, those with lower mtDNA content suffered from a 2.48-fold increased risk of recurrence [95% confidence interval (CI) 1.082-5.694, P = 0.032]. The quartile analyses exhibited a significant dose relationship for this association (P-for (trend) = 0.042). Nevertheless, we failed to draw similar significant conclusions from mtDNA content in tumor but only got a trend. Additionally, receiver operating characteristic (ROC) curve analysis presented a valuable diagnostic potential for the ratio of the mtDNA content in tumor to that in corresponding peritumoral tissues (T/P ratio) to predict HCC recurrence. This model achieved a sensitivity of 0.44 and a specificity of 0.97 with the area under ROC curve (AUC) of 0.754. HCC patients with higher T/P ratio exhibited a significantly worse 5-year recurrence-free survival. In summary, peritumoral tissues mtDNA is a potential biomarker for predicting HCC recurrence risk in HBV patients. T/P ratio could serve as a novel feasible predictor for recurrence and an independent prognosis marker in HBV-infected HCC patients.