Abstract
Hepatocellular carcinoma (HCC) accounts for 70–85% of liver cancer, and about 85% of HCC are hepatitis B virus-related (HBV-HCC) in China. Transarterial chemoembolization (TACE) combined with traditional Chinese medicine (TCM) has been reported as an effective treatment. Potential biomarkers to stratify patients who may benefit from this treatment are needed. In this study, we aimed to evaluate whether circulating cell-free mitochondrial DNA (ccf-mtDNA) content was associated with the outcome of HCC patients, especially of those who received the combination treatment of TACE and TCM. Univariate and multivariate Cox analyses were conducted to evaluate the association between ccf-mtDNA content and the overall survival of HBV-HCC patients. Kaplan–Meier analysis was used to compare the survival differences between patients with low and high ccf-mtDNA content. In a hospital-based cohort with 141 HBV-HCC patients, there was no statistically significant association between the ccf-mtDNA content and the overall survival of HBV-HCC patients in the univariate analysis, but a borderline significant association was found in the multivariate analyses. In a subcohort of 50 HBV-HCC patients who received TACE and TCM treatment, high ccfDNA content conferred an increased death risk with a hazard ratio of 4.01 (95% confidence interval: 1.25–12.84, p = 0.019) in the multivariate analysis. Kaplan–Meier survival analysis also showed that patients with high ccf-mtDNA content had unfavorable survival (log rank p = 0.097). Our findings suggest that ccf-mtDNA content is a potential non-invasive prognostic biomarker in HCC patients receiving TACE and TCM treatment.
Highlights
Hepatocellular carcinoma (HCC) is the second leading cause of cancer death, and chronic hepatitis B virus (HBV) infection accounts for at least 50% of HCC cases worldwide (Xie, 2017)
There were 45 (31.9%) patients who developed liver cirrhosis and 117 (83.0%) patients with a B or C Child–Pugh class. Among these 141 HBV-HCC patients, 70 (49.6%) patients were treated with Transarterial chemoembolization (TACE), 59 (41.8%) patients were treated with traditional Chinese medicine (TCM), and 50 (35.4%) patients received a combination therapy of TACE and TCM
A previous study showed that a low ccf-mtDNA content was associated with an increased risk for developing HBV-HCC (Li et al, 2016), while the current study suggested that the high level of ccf-mtDNA was associated with the poor outcome of HBV-HCC patients receiving TACE combined with TCM
Summary
Hepatocellular carcinoma (HCC) is the second leading cause of cancer death, and chronic hepatitis B virus (HBV) infection accounts for at least 50% of HCC cases worldwide (Xie, 2017). Mitochondrial dysfunction plays an important role in the occurrence and development of liver cancer (Xiong et al, 2012; Dilip et al, 2013), and when mitochondrial dysfunction causes mtDNA damage, the mtDNA fragments can escape from the matrix and enter the cytosol or systemic circulation (Wenceslau et al, 2014). Circulating mtDNA was suggested to be a novel non-invasive biomarker for cancer diagnosis and prognostic evaluation due to its specific and unique characteristics (Li et al, 2016; Weerts et al, 2018), for example, the study of Li et al (2016) showed that the serum ccf-mtDNA content of HBV-HCC patients was significantly lower than that of cancer-free HBV controls, and compared to HBV patients with high mtDNA content, those with low mtDNA content had a significantly increased risk of HCC. The association of ccf-mtDNA content with the clinical outcomes of HCC patients remains largely unknown
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