Prediction of response to treatment by gene expression profiling of peripheral blood in patients with microscopic polyangiitis.
Prediction of response to treatment by gene expression profiling of peripheral blood in patients with microscopic polyangiitis.
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DOI：
10.1371/journal.pone.0063182
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
JMAAV
中科院分区：
文献类型：
--
作者：
Ishizu A;Tomaru U;Murai T;Yamamoto T;Atsumi T;Yoshiki T;Yumura W;Yamagata K;Yamada H;Kumagai S;Kurokawa MS;Suka M;Makino H;Ozaki S;JMAAV
JMAAV研究是一项开放标签的前瞻性临床试验，为显微镜下多血管炎(MPA)患者提出了基于严重程度的治疗方案。结果表明，建议的方案是有用的(缓解率：89.4%)，但也指示复发或患者死亡(复发率：19.0%；死亡率：10.6%)。本研究的目的是开发一种预测治疗效果的方法。在本研究中，采用JMAAV研究患者的外周血进行转录组分析，分别在治疗开始前和治疗开始后一周进行。治疗前的基因表达谱与治疗反应无直接关系。然而，当对9例应答良好(持续缓解18个月)的患者的样本进行检测时，治疗后88个基因的表达发生了显著变化。选择30个统计可靠的基因，检测22例患者治疗前后基因表达的变化，其中17例反应良好，定义为持续缓解18个月，5例反应差，定义为缓解后复发或未缓解。对治疗引起的30个基因的表达变化和治疗反应之间的辨别分析发现，16个基因的组合是预测治疗反应的最有价值的基因集。这项初步研究确定IRF7、IFIT1、IFIT5、OASL、ClC、GBP-1、PSMB9、HERC5、CCR1、CD36、MS4A4A、BIRC4BP、PLSCR1、DEFA1/DEFA3、DEFA4和COL9A2是在治疗早期预测治疗效果的重要基因。
The JMAAV study was an open-labeled prospective clinical trial, which proposed severity-based treatment protocols for patients with microscopic polyangiitis (MPA). The results suggest that the proposed protocols are useful (remission rate: 89.4%), but are also indicative of relapse or patient demise regardless of the treatment (recurrence rate: 19.0%; mortality rate: 10.6%). The aim of this study is to develop the method to predict response to the treatment in patients with MPA. In the present study, transcriptome analysis was performed using peripheral blood from patients enrolled in the JMAAV study before and 1-week after the beginning of treatment. The gene expression profile before treatment was not directly related to the response to the treatment. However, when the samples from 9 patients with good response (persistent remission for 18 months) were examined, the expression of 88 genes was significantly altered by the treatment. Thirty statistically reliable genes were selected, and then the alteration of expression by the treatment was examined among 22 patients, including 17 with good response, which was defined as persistent remission for 18 months and 5 with poor response, which was defined as relapse after remission or no remission. Discrimination analysis between the alteration of expression of the 30 genes by the treatment and the response identified a combination of 16 genes as the most valuable gene set to predict the response to the treatment. This preliminary study identified IRF7, IFIT1, IFIT5, OASL, CLC, GBP-1, PSMB9, HERC5, CCR1, CD36, MS4A4A, BIRC4BP, PLSCR1, DEFA1/DEFA3, DEFA4, and COL9A2 as the important genes that can predict the response to the treatment in patients with MPA at an early point during the therapy.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5.4
作者：
Chaussabel D;Pascual V;Banchereau J
通讯作者：
Banchereau J
影响因子：
4.1
作者：
Ishii, Taeko;Onda, Hiroaki;Nojima, Hiroshi
通讯作者：
Nojima, Hiroshi
影响因子：
2.2
作者：
Ozaki S;Atsumi T;Hayashi T;Ishizu A;Kobayashi S;Kumagai S;Kurihara Y;Kurokawa MS;Makino H;Nagafuchi H;Nakabayashi K;Nishimoto N;Suka M;Tomino Y;Yamada H;Yamagata K;Yoshida M;Yumura W;Amano K;Arimura Y;Hatta K;Ito S;Kikuchi H;Muso E;Nakashima H;Ohsone Y;Suzuki Y;Hashimoto H;Koyama A;Matsuo S;Kato H
通讯作者：
Kato H
影响因子：
7
作者：
Vrieze, Scott I.
通讯作者：
Vrieze, Scott I.