Objective To investigate the relationship of mitochondrial DNA (mtDNA) copy number with clinicopathologic characteristics and its influence on the prognosis of hepatocellular carcinoma (HCC) patients.

Methods The retrospective case-control study was conducted. The clinicopathological data of 71 HCC patients undergoing surgical treatment in the Eastern Hepatobiliary Surgery Hospital of Naval Medical University from March to June 2011 were collected. There were 61 males and 10 females, aged from 26 to 80 years, with a median age of 55 years. The mtDNA copy number of tumor tissues and adjacent normal tissues were measured for all patients. Observation indicators: (1) the mtDNA copy number of tumor tissues and adjacent normal tissues and relationship between the mtDNA copy number and clinicopathological characteristics of HCC patients; (2) follow-up; (3) related factors for the prognosis of HCC patients. Follow-up using outpatient examination or telephone interview was conducted to detect postoperative survival of patients up to September 2019. Measurement data with normal distribution were described as Mean±SD, and comparison between groups was analyzed using independent samples t test or the matched samples t test. Measurement data with skewed distribution were described as M(range). Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Univariate and multivariate analyses were conducted using the COX regressional model. Variables with P<0.10 in the univariate analysis were included for the multivariate analysis. Survival rates were calculated using the Kaplan-Meier method, and Log-rank test was used for survival analysis.

Results (1) The mtDNA copy number of tumor tissues and adjacent normal tissues and relationship between the mtDNA copy number and clinicopathological characteristics of HCC patients: of 71 HCC patients, the mtDNA copy number was 0.85±0.08 in tumor tissues, versus 1.16±0.08 in adjacent normal tissues, showing a significant difference between them (t=2.96, P<0.05). Of 71 HCC patients, 48 cases were mtDNA-low and 23 cases were mtDNA-high. Cases with tumor capsule as integrity or not-integrity, cases with or without microvascular (MVI) in mtDNA-low and mtDNA-high patients were 20, 28, 21, 27 and 16, 7, 4, 19, respectively, showing significant differences (χ²=4.84, 4.74, P<0.05). (2) Follow-up: 71 patients were followed up for 2.1 to 85.3 months, with a median follow-up time of 47.8 months. The 1-, 3-, 5-year overall survival rates of 71 HCC patients were 87.3%, 64.7, 37.4%, respectively. Moreover, the 1-, 3-, 5-year overall survival rates were 81.2%, 50.0%, 29.2% of the mtDNA-low patients, versus 95.7%, 86.5%, 54.7% of the mtDNA-high patients, showing a significant difference between the two groups (χ²=5.86, P<0.05). (3) Related factors for the prognosis of HCC patients. Results of univariate analysis showed that the number of tumor, portal vein tumor thrombus, MVI, Barcelona Clinic Liver Cancer stage, mtDNA copy number were related factors for the prognosis of HCC patients (hazard ratios=2.211, 2.911, 3.899, 3.587, 0.440, 95% confidence intervals as 1.024‒4.777, 1.485‒5.704, 2.115‒7.186, 1.615‒7.966, 0.223‒0.871, P<0.05). Results of multivariate analysis showed that MVI and mtDNA copy number were independent influencing factors for the prognosis of HCC patients (hazard ratios=2.754, 0.437, 95% confidence intervals as 1.374‒5.521, 0.205‒0.932, P<0.05).

Conclusions The mtDNA copy number of HCC patients is related with tumor capsule and MVI. The mtDNA copy number and MVI are independent influencing factors for the prognosis of HCC patients.