原发性肝细胞癌经动脉化疗栓塞术（TACE）后血浆游离DNA（cfDNA）与预后的关系
Relationship between plasma cell-free DNA (cfDNA) and prognosis of TACE for primary hepatocellular carcinoma.
作者信息
Ma Kun, Liu Jiayun, Wang Youjin, Zhong Yubin, Wu Zhenfeng, Fan Ruiying, Guo Shanfeng
机构信息
Department of Interventional Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
出版信息
J Gastrointest Oncol. 2020 Dec;11(6):1350-1363. doi: 10.21037/jgo-20-509.
BACKGROUND
Our study aims to investigate changes in cell-free DNA (cfDNA) concentration and integrity in primary hepatocellular carcinoma (PHC) patients before and after transcatheter arterial chemoembolization (TACE) treatment and their influence on the evaluation of prognosis of the disease.
METHODS
A total of 84 PHC patients admitted to the Affiliated Hospital of Nanjing University of Chinese Medicine from December 2016 to December 2017 were included as the study group, while 55 healthy people served as the control group. Plasma cfDNA concentration and integrity were determined using qRT-PCR. The correlation between cfDNA concentration/integrity and clinical characteristics of PHC patients were analyzed. A ROC curve was used to investigate the sensitivity and specificity of cfDNA as detection indices. Univariate and multivariate analyses were used to analyze factors affecting recurrence in PHC patients and compare recurrence-free survival (RFS) of PHC patients with high cfDNA expression and low cfDNA expression.
RESULTS
Plasma cfDNA concentration and integrity were significantly higher in PHC patients before TACE treatment than in healthy people and significantly lower after treatment than before (P<0.05). The cfDNA concentration was significantly correlated with tumor size, lymph node metastasis, TNM stage, and BCLC stage, while cfDNA integrity was significantly correlated with tumor size, TNM stage, and BCLC stage (P<0.05). ROC results showed that the area under the curve (AUC) value of cfDNA concentration was the largest, with an optimal cut-off of 10.51 ng/mL. Multivariate regression analysis for COX showed that the TNM stage, cfDNA concentration, and AFP were independent risk factors that affected PHC patients' survival.
CONCLUSIONS
Plasma cfDNA concentration in PHC patients is more sensitive and specific than any other tumor marker. It is an independent risk factor for PHC patients treated with TACE. Therefore, it is hypothesized cfDNA is a potential biomarker for prognostic evaluation of PHC patients treated with TACE.
背景
本研究旨在探讨原发性肝细胞癌（PHC）患者经肝动脉化疗栓塞术（TACE）治疗前后游离DNA（cfDNA）浓度及完整性的变化及其对疾病预后评估的影响。
方法
选取2016年12月至2017年12月在南京中医药大学附属医院收治的84例PHC患者作为研究组，另选55例健康人作为对照组。采用qRT-PCR法测定血浆cfDNA浓度及完整性。分析cfDNA浓度/完整性与PHC患者临床特征的相关性。采用ROC曲线研究cfDNA作为检测指标的敏感性和特异性。采用单因素和多因素分析方法分析影响PHC患者复发的因素，并比较cfDNA高表达和低表达的PHC患者的无复发生存期（RFS）。
结果
PHC患者TACE治疗前血浆cfDNA浓度及完整性显著高于健康人，治疗后显著低于治疗前（P<0.05）。cfDNA浓度与肿瘤大小、淋巴结转移、TNM分期及BCLC分期显著相关，而cfDNA完整性与肿瘤大小、TNM分期及BCLC分期显著相关（P<0.05）。ROC结果显示，cfDNA浓度的曲线下面积（AUC）值最大，最佳截断值为10.51 ng/mL。COX多因素回归分析显示，TNM分期、cfDNA浓度及甲胎蛋白是影响PHC患者生存的独立危险因素。
结论
PHC患者血浆cfDNA浓度比其他任何肿瘤标志物更敏感、更具特异性。它是接受TACE治疗的PHC患者的独立危险因素。因此，推测cfDNA是接受TACE治疗的PHC患者预后评估的潜在生物标志物。
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