中国医师协会病理科医师分会

Chinese Pathologist Association
循环肿瘤细胞DNA预测肝癌复发

  

循环肿瘤细胞DNA预测肝癌复发


根据最近公布的数据显示,广岛大学的研究人员发现,循环肿瘤细胞DNA是能够准确预测肝切除术后2年内肝细胞癌复发的一个因子。

“我们发现,循环肿瘤细胞DNA水平能够准确反映肝细胞癌的肿瘤进程和治疗效果,”广岛大学Atsushi Ono博士在新闻发布会上说。“通过进一步的研究,循环肿瘤细胞DNA的基因组图谱分析,可能会指导肝细胞癌的个体化管理。”

Ono及其同事分析了46例肝癌患者的数据,这些患者都在2009年10月至2012年1月之间行肝切除或肝移植手术。研究人员通过使用针对每个肿瘤通过针对每个肿瘤体细胞重排测定量化了循环肿瘤细胞DNA(ctDNA)。外显子测序也采用游离DNA配对行肝动脉化疗栓塞术(TACE)后复发性肝癌患者的原发肿瘤组织中的DNA。

“我们研究了ctDNA水平能否反映肝脏肿瘤的动态,以及能否通过量化每个特定肿瘤基因组排序作为不良诊断的一个预测因子,”研究人员写道。“我们还在研究肝癌患者游离DNA基因组外显子测序能否识别癌组织的体细胞突变。”

突变可以发生在所有的肿瘤中;然而,术前46例患者中仅有7例有ctDNA。ctDNA的存在与肿瘤体积大和肝切除术后2年内肝癌的复发是相关联的。此外,ctDNA也会随着疾病进展而增加。

与没有ctDNA的患者(P=0.0386)相比,存在ctDNA的患者复发和肝外转移的累积发生率较低(P=0.0102)。

多因素分析显示ctDNA是门静脉显微血管受侵犯的一个独立预测因子(OR=6.1;95% CI,1.11-33.33)。

此外,研究人员通过外显子测序在TACE术后游离DNA中发现了45个非同义突变,在原发肿瘤组织中发现率71个非同义体细胞突变。在两个样本都有25个常见的基因突变,在原发肿瘤组织中发现的突变中有85%在游离DNA也有发现。

“ctDNA的存在反映了肿瘤的进展,检测到ctDNA可以预测门静脉血管受侵犯及复发,尤其对于在2年内发生肝外转移的患者。我们的研究表明ctDNA检测和游离DNA的测序分析对肝癌个体化治疗是十分有用的。”–by Melinda Stevens






英文原文    Circulating tumor DNA may predict HCC recurrence



Researchers at Hiroshima University found circulating tumor DNA to be an accurate predictor of hepatocellular carcinoma recurrence within 2 years of liver resection, according to newly published data.

“We uncovered that circulating tumor DNA levels accurately reflect cancer progression and therapy effects on hepatocellular carcinoma,” Atsushi Ono, MD, Hiroshima University, said in a press release. “With further research, the identification of genome profiles through circulating tumor DNA analysis may guide individualized management of hepatocellular carcinoma.”

Ono and colleagues analyzed data of 46 patients with HCC who underwent hepatectomy or liver transplantation between October 2009 and January 2012. The researchers quantified circulating tumor DNA (ctDNA) through the use of assays that targeted somatic rearrangements of each tumor. Exome sequencing also was performed using cell-free DNA paired primary tumor tissue DNA from a patient with recurrent liver cancer after transcatheter arterial chemoembolization (TACE).

“We investigated whether ctDNA levels reflect HC tumor dynamics and could be used as a predictor of poor diagnosis by quantifying each of the cancer-specific genomic arrangements,” the researchers wrote. “We have also investigated whether exome sequencing of cell-free DNA in a patient with liver cancer could identify somatic mutations in cancer tissue.”

Mutations were found in all of the tumors; however, ctDNA was found in only seven of the 46 patients before surgery. The presence of ctDNA was associated with larger tumor size and increased recurrence for HCC within 2 years of liver resection. In addition, ctDNA also increased with disease progression.

The cumulative incidence of recurrence and extrahepatic metastasis in the patients with ctDNA (P = .0102) was worse compared with the patients without ctDNA (P = .0386).


Multivariate analysis showed ctDNA to be an independent predictor of microscopic vascular invasion of the portal vein (OR = 6.1; 95% CI, 1.11-33.33).

In addition, the researchers found 45 nonsynonymous somatic mutations in cell-free DNA after TACE and 71 nonsynonymous somatic mutations in primary tumor tissue by exome sequencing. There were 25 common mutations in both samples, with 83% of mutations identified in the primary tumor also detectable in the cell-free DNA.

“The presence of ctDNA reflects tumor progression, and detection of ctDNA can predict [vascular invasion of the portal vein] and recurrence, especially extrahepatic metastasis within 2 years. Our study demonstrated the usefulness of ctDNA detection and sequencing analysis of cell-free DNA for personalized treatment of liver cancer.” – by Melinda Stevens


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