Gene Expression in Hepatocellular Carcinoma: Pilot Study of Potential Transarterial Chemoembolization Response Biomarkers
Gene Expression in Hepatocellular Carcinoma: Pilot Study of Potential Transarterial Chemoembolization Response Biomarkers
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DOI：
10.1016/j.jvir.2014.12.610
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发表时间：
2015-05-01
影响因子：
2.9
通讯作者：
Casadaban, Leigh C.
中科院分区：
文献类型：
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作者：
Gaba, Ron C.;Groth, John V.;Casadaban, Leigh C.
目的：执行。一项可行性研究，旨在探讨肝细胞癌遗传学与经动脉化疗栓塞治疗反应之间的关系，以确定与增强治疗效果相关的潜在生物标志物。材料和方法：在这项单机构研究中，对 2007 年至 2013 年间接受化疗栓塞治疗的 19 名患者（14 名男性，5 名女性；平均年龄 59 岁）的治疗前肝细胞癌肿瘤活检标本进行了小组分析使用 QuantiGene Plex 2.0 mRNA 检测分析检测 60 个化疗敏感性、缺氧、有丝分裂和炎症基因。人口统计、疾病；并收集手术数据和肿瘤反应结果。根据表现出完全缓解 (CR) 与部分缓解 (PR) 的肿瘤之间的放射学反应来比较定量 mRNA 水平。 结果：研究样本包括平均接受两次传统化疗栓塞治疗的患者的 19 份肿瘤活检标本（平均大小 3.0 cm；1 级，n = 6；2 级，n = 9；3 级，n = 4）。平均治疗后 116 天，13 个和 6 个肿瘤分别表现出 CR 和 PR。与 PR 肿瘤相比，CR 肿瘤的治疗前化疗敏感性和有丝分裂（ATF4、BAX、CCNE1、KIF11、NFX1、PPP3CA、SNX1、TOP2A 和 TOP2B）基因 mRNA 表达显着增加（P < .05）或趋势（P < .1）更大（范围，1.49-3.50 倍），此外 CXCL10 水平较低（0.48 倍），并且显着（P < .05）更高（1.65 倍）基线 VEGFA 水平。结论：遗传特征可能允许对肿瘤反应概率进行化疗栓塞前分层，因此基因分析可能提供通过增强治疗方式分配来个性化局部治疗的机会。有必要进一步证实已识别的标记并探索它们各自的预测能力阈值。
Purpose: To perform. a feasibility study to explore the relationship between hepatocellular carcinoma genetics and transarterial chemoembolization treatment response to identify potential biomarkers associated with enhanced treatment efficacy.Materials and Methods: In this single-institution study, pretreatment hepatocellular carcinoma biopsy specimens for tumors in 19 patients (14 men, five women; mean age, 59 y) treated with chemoembolization between 2007 and 2013 were analyzed for a panel of 60 chemotherapy-sensitivity, hypoxia, mitosis, and inflammatory genes with the QuantiGene Plex 2.0 mRNA detection assay. Demographic, disease; and procedure data and tumor response outcomes were collected. Quantitative mRNA levels were compared based on radiologic response between tumors exhibiting complete response (CR) versus partial response (PR).Results: The study sample included 19 biopsy specimens from tumors (mean size, 3.0 cm; grade 1, n = 6; grade 2, n = 9; grade 3, n = 4) in patients treated with a mean of two conventional chemoembolization sessions. Thirteen and six tumors exhibited CR and PR, respectively, at a mean of 116 days after treatment. Tumors with CR showed a significant increase in (P < .05) or trend toward (P < .1) greater (range, 1.49-3.50 fold) pretreatment chemotherapy-sensitivity and mitosis (ATF4, BAX, CCNE1, KIF11, NFX1, PPP3CA, SNX1, TOP2A, and TOP2B) gene mRNA expression compared with tumors with PR, in addition to lower CXCL10 levels (0.48-fold), and had significantly (P < .05) higher (1.65-fold) baseline VEGFA levels.Conclusions: Genetic signatures may allow prechemoembolization stratification of tumor response probability, and gene analysis may therefore offer an opportunity to personalize locoregional therapy by enhancing treatment modality allocation. Further corroboration of identified markers and exploration a their respective predictive capacity thresholds is necessary.