Li Shilai, Wan Peiqi, Peng Tao, Xiao Kaiyin, Su Ming, Shang Liming, Xu Banghao, Su Zhixiong, Ye Xinping, Peng Ning, Qin Quanlin, Li Lequn
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Oncol Lett. 2016 Jun;11(6):3723-3728. doi: 10.3892/ol.2016.4466. Epub 2016 Apr 19.
The association between mitochondrial DNA (mtDNA) polymorphisms or mutations and the prognoses of cancer have been investigated previously, but the results have been ambiguous. In the present study, the associations between sequence variations in the mtDNA D-loop region and the outcomes of patients with hepatocellular carcinoma (HCC) were analysed. A total of 140 patients with HCC (123 males and 17 females), who were hospitalised to undergo radical resection, were studied. Polymerase chain reaction and direct sequencing were performed to detect the sequence variations in the mtDNA D-loop region. Multivariate and univariate analyses were conducted to determine important factors in the prognosis of HCC. A total of 150 point sequence variations were observed in the 140 cases (13 point mutations, 8 insertions, 20 deletions and 116 polymorphisms). The variation rate was 13.4% (150/1, 122). mtDNA nucleotide 150 (C/T) was an independent factor in the logistic regression for early/late recurrence of HCC. Patients with 150T appeared to have later recurrences. In a Cox proportional hazards regression model, hepatitis B virus DNA, Child-Pugh class, differentiation degree, tumour-node-metastasis (TNM) stage, nucleotide 16263 (T/C) and nucleotide 315 (N/insertion C) were independent factors for tumour-free survival time. Patients with the 16263T allele had a greater tumour-free survival time than patients with the 16263C allele. Similarly, patients with 315 insertion C had a superior tumour-free survival time when compared with patients with 315 N (normal). In the Cox proportional hazards regression model, recurrence type (early/late), Child-Pugh class, TNM stage and adjuvant treatment after tumour recurrence (none or one/more than one treatment) were independent factors for overall survival. None of the mtDNA variations served as independent factors. Patients with late recurrence, Child-Pugh class A, and low TNM stages and/or those who received more than one adjuvant treatment following tumour recurrence had favourable outcomes. mtDNA D-loop polymorphisms were associated with early recurrence and tumour-free survival time, but not with overall survival. mtDNA D-loop mutations in HCC were infrequent and lacked prognostic utility. The detection of mtDNA D-loop polymorphisms may assist in identifying risk factors for HCC prognosis, particularly for the short-term outcome, thereby aiding the construction of an appropriate therapeutic strategy.
线粒体DNA（mtDNA）多态性或突变与癌症预后之间的关联此前已被研究，但结果并不明确。在本研究中，分析了mtDNA D环区域的序列变异与肝细胞癌（HCC）患者预后之间的关联。共研究了140例因接受根治性切除术而住院的HCC患者（123例男性和17例女性）。采用聚合酶链反应和直接测序法检测mtDNA D环区域的序列变异。进行多因素和单因素分析以确定HCC预后的重要因素。140例患者中共观察到150个点序列变异（13个点突变、8个插入、20个缺失和116个多态性）。变异率为13.4%（150/1122）。mtDNA核苷酸150（C/T）是HCC早期/晚期复发逻辑回归中的独立因素。携带150T的患者复发时间似乎较晚。在Cox比例风险回归模型中，乙肝病毒DNA、Child-Pugh分级、分化程度、肿瘤-淋巴结-转移（TNM）分期、核苷酸16263（T/C）和核苷酸315（N/插入C）是无瘤生存时间的独立因素。携带16263T等位基因的患者无瘤生存时间比携带16263C等位基因的患者更长。同样，与携带315 N（正常）的患者相比，携带315插入C的患者无瘤生存时间更优。在Cox比例风险回归模型中，复发类型（早期/晚期）、Child-Pugh分级、TNM分期和肿瘤复发后的辅助治疗（无或一种/一种以上治疗）是总生存的独立因素。没有mtDNA变异作为独立因素。复发晚、Child-Pugh A级、TNM分期低和/或肿瘤复发后接受一种以上辅助治疗的患者预后良好。mtDNA D环多态性与早期复发和无瘤生存时间相关，但与总生存无关。HCC中mtDNA D环突变很少见且缺乏预后价值。检测mtDNA D环多态性可能有助于识别HCC预后的危险因素，特别是对于短期预后，从而有助于制定合适的治疗策略。
