Distinct outcome of stage I lung adenocarcinoma with ACTN4 cell motility gene amplification
Distinct outcome of stage I lung adenocarcinoma with ACTN4 cell motility gene amplification
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DOI：
10.1093/annonc/mdt293
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发表时间：
2013-10-01
影响因子：
50.5
通讯作者：
Yamada, T.
中科院分区：
文献类型：
--
作者：
Noro, R.;Honda, K.;Yamada, T.
即使在早期阶段被发现，相当数量的肺癌在根治手术后会复发。在543例手术切除的肺腺癌组织芯片上，用荧光原位杂交技术检测了ACTN4基因的拷贝数。在7个肺腺癌细胞系中的2个细胞系和543例病理I-IV期肺腺癌中79例(15%)发现ACTN4基因的扩增(拷贝数增加2.0倍)。多因素分析显示，在290例I期肺腺癌患者中，ACTN4基因扩增是最显著的独立危险因素(危险比为6.78；P=9.48×10(-5)，COX回归分析)。ACTN基因扩增的预后意义在三个独立队列中得到进一步验证，共1033名患者。ACTN4基因扩增定义了一小部分I期肺腺癌患者，显示出不同的预后。这类患者需要加强医疗护理，并可能从术后辅助化疗中受益。
Even if detected at an early stage, a substantial number of lung cancers relapse after curative surgery. However, no method for distinguishing such tumors has yet been established.The copy number of the actinin-4 (ACTN4) gene was determined by fluorescence in situ hybridization on tissue microarrays comprising 543 surgically resected adenocarcinomas of the lung.Amplification (an increase in the copy number by >= 2.0 fold) of the ACTN4 gene was detected in two of seven lung adenocarcinoma cell lines and 79 (15%) of 543 cases of pathological stage I-IV lung adenocarcinoma. Multivariate analysis revealed that ACTN4 gene amplification was the most significant independent factor associated with an extremely high risk of death (hazard ratio, 6.78; P = 9.48 x 10(-5), Cox regression analysis) among 290 patients with stage I lung adenocarcinoma. The prognostic significance of ACTN gene amplification was further validated in three independent cohorts totaling 1033 patients.Amplification of the ACTN4 gene defines a small but substantial subset of patients with stage I lung adenocarcinoma showing a distinct outcome. Such patients require intensive medical attention and might benefit from postoperative adjuvant chemotherapy.