Targeted DNA and RNA sequencing of fine-needle biopsy FFPE specimens in patients with unresectable hepatocellular carcinoma treated with sorafenib.
Targeted DNA and RNA sequencing of fine-needle biopsy FFPE specimens in patients with unresectable hepatocellular carcinoma treated with sorafenib.
复制标题
用索拉非尼治疗的无法切除的肝细胞癌癌的患者中细针活检FFPE标本的靶向DNA和RNA测序。
DOI：
10.18632/oncotarget.4270
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发表时间：
2015-08-28
期刊：
影响因子：
--
通讯作者：
Osaki Y
中科院分区：
文献类型：
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作者：
Sakai K;Takeda H;Nishijima N;Orito E;Joko K;Uchida Y;Izumi N;Nishio K;Osaki Y
多激酶抑制剂索拉非尼现在被用作晚期肝细胞癌（HCC）的标准治疗。因此，对索拉非尼的反应的预测性生物标志物是必要的。本研究的目的是评估使用靶向DNA和RNA测序来阐明肝癌患者中使用细针活检、福尔马林固定石蜡包埋（FFPE）标本的索拉非尼应答的候选生物标志物的可行性。靶向DNA和RNA深度测序可用于评估46例接受索拉非尼治疗的HCC患者的细针活检FFPE标本。在肝癌组织中，CTNNB 1（34.8%）和TP 53（26.1%）等抑癌基因突变频率较高。在排除这些抑制基因后，检测到的癌基因突变的平均数量在非PD组和PD组之间存在显著差异（P = 0.0446）。这一结果表明，肿瘤中的癌基因突变负荷可能与索拉非尼的临床反应有关。我们已经通过RNA测序鉴定了肿瘤中用于预测索拉非尼反应和PFS的候选基因表达（TGF α、PECAM 1和NRG 1）。我们的研究结果为索拉非尼治疗的生物标志物提供了新的见解，并使我们能够讨论未来的治疗策略。
The multi-kinase inhibitor sorafenib is now used as standard therapy for advanced hepatocellular carcinoma (HCC). Predictive biomarkers of response to sorafenib are thus necessary. The purpose of this study was to assess the feasibility of using targeted DNA and RNA sequencing to elucidate candidate biomarkers of sorafenib response using fine-needle biopsy, formalin-fixed paraffin-embedded (FFPE) specimens in patients with HCC. Targeted DNA and RNA deep sequencing were feasible for the evaluation of fine-needle biopsy FFPE specimens obtained from 46 patients with HCC treated with sorafenib. Frequent mutations of suppressor genes, such as CTNNB1 (34.8%) and TP53 (26.1%), were detected in the HCC tumors. After excluding these suppressor genes, the average numbers of detected oncogene mutations differed significantly between the non-PD and PD groups (P = 0.0446). This result suggests that the oncogene mutational burden in the tumor might be associated with the clinical response to sorafenib. We have identified candidate gene expression (TGFa, PECAM1, and NRG1) in tumor for the prediction of sorafenib response and PFS by RNA sequencing. Our findings provide new insights into biomarkers for sorafenib therapy and allow us to discuss future therapeutic strategies.