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CMGH:新型肝癌DNA检测手段或改善患者生存率

来源:生物谷 2015-09-14 13:42

2015年9月14日 讯 /生物谷BIOON/ --一篇发表于国际杂志Cellular and Molecular Gastroenterology and Hepatology上的研究论文中,来自广岛大学的研究人员通过研究表示,对患者手术前血清样本中的循环肿瘤DNA进行检测或可帮助预测患者肝细胞癌的早期复发以及帮助指导疗法的进行;肝细胞癌是一种常见类型的肝癌,其也是世界上引发癌症死亡的主要癌症。

研究者Atsushi Ono教授表示,我们发现,循环肿瘤DNA的水平可以准确反映肝细胞癌的进展以及疗法的效应,随着更深一步的研究,通过对循环肿瘤DNA的分析来进行的基因组特性的鉴别或可帮助指导个体化疗法以及管理策略的开展。研究者对46名正在进行肝细胞癌切除疗法额患者的机体的全基因组进行测序,同时获取患者在术前和术后的血清样本,随后研究者对比了患者机体正常的DNA和肿瘤细胞DNA的差异,在所有的46份样本中发现了DNA的突变信息。

当突变在所有肿瘤中存在时,研究者仅在7名患者的血清中检测到了循环肿瘤DNA的存在,而循环肿瘤DNA的存在和肿瘤尺寸增加及切除术后2年内肿瘤复发直接相关;血清中循环肿瘤DNA的水平同样也可以随着疾病的进展而增加,并且可以帮助反映疗法的反应。肝细胞癌通常在患者晚期才能够被检测出来,而且患者的5年生存率仅为11%,因此鉴别出一种新型方法或许就可以帮助监测疾病进展,并且鉴别出那些因疗法而获益的患者,当然这对于改善干细胞癌患者的生存率非常关键。

最后研究者Jerrold R. Turner博士表示,对循环肿瘤DNA的分析可以反映肝癌个体化疗法潜在模式的转变,我们希望后期可以进行更多研究获取更有鼓励性的价值来帮助最终改善治疗恶性肝细胞癌的有效疗法。(生物谷Bioon.com)

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Circulating Tumor DNA Analysis for Liver Cancers and Its Usefulness as a Liquid Biopsy

Atsushi Ono, Akihiro Fujimoto, Yujiro Yamamoto, Sakura Akamatsu, Nobuhiko Hiraga, Michio Imamura, Tomokazu Kawaoka, Masataka Tsuge, Hiromi Abe, C. Nelson Hayes, Daiki Miki, Mayuko Furuta, Tatsuhiko Tsunoda, Satoru Miyano, Michiaki Kubo, Hiroshi Aikata, Hidenori Ochi, Yoshi-iku Kawakami, Koji Arihiro, Hideki Ohdan, Hidewaki Nakagawa, Kazuaki Chayama

Background & Aims Circulating tumor DNA (ctDNA) carrying tumor-specific sequence alterations has been found in the cell-free fraction of blood. Liver cancer tumor specimens are difficult to obtain, and noninvasive methods are required to assess cancer progression and characterize underlying genomic features. Methods We analyzed 46 patients with hepatocellular carcinoma who underwent hepatectomy or liver transplantation and for whom whole-genome sequencing data was available. We designed personalized assays targeting somatic rearrangements of each tumor to quantify serum ctDNA. Exome sequencing was performed using cell-free DNA paired primary tumor tissue DNA from a patient with recurrent liver cancer after transcatheter arterial chemoembolization (TACE). Results We successfully detected ctDNA from 100 μL of serum samples in 7 of the 46 patients before surgery, increasing with disease progression. The cumulative incidence of recurrence and extrahepatic metastasis in the ctDNA-positive group were statistically significantly worse than in the ctDNA-negative group (P = .0102 and .0386, respectively). Multivariate analysis identified ctDNA (OR 6.10; 95% CI, 1.11–33.33, P = .038) as an independent predictor of microscopic vascular invasion of the portal vein (VP). We identified 45 nonsynonymous somatic mutations in cell-free DNA after TACE and 71 nonsynonymous somatic mutations in primary tumor tissue by exome sequencing. We identified 25 common mutations in both samples, and 83% of mutations identified in the primary tumor could be detected in the cell-free DNA. Conclusions The presence of ctDNA reflects tumor progression, and detection of ctDNA can predict VP 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.

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