Gene-expression profiles correlate with the efficacy of anti-EGFR therapy and chemotherapy for colorectal cancer
Gene-expression profiles correlate with the efficacy of anti-EGFR therapy and chemotherapy for colorectal cancer
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DOI：
10.1007/s10147-015-0841-4
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发表时间：
2015-12-01
影响因子：
3.3
通讯作者：
Ishioka, Chikashi
中科院分区：
文献类型：
--
作者：
Inoue, Masahiro;Takahashi, Shin;Ishioka, Chikashi
全面的基因表达分析对于根据特定癌症的生物学特征将其划分为亚组非常有用；它既可用于预测，也可用于预测。本研究的目的是通过福尔马林固定的石蜡包埋组织的基因表达谱对不能切除的晚期或复发性结直肠癌(CRC)进行分类，并将CRC亚型与临床病理、分子特征和临床结果相关联。从FFPE组织中提取RNA进行基因表达微阵列分析，通过无监督的系统聚类将患者分为四个亚型(A1、A2、B1和B2亚型)。主成分分析(PCA)将患者分为A、B亚型和1、2亚型。A亚型在无KRAS突变且临床分期较早的患者中显著丰富。在抗表皮生长因子受体治疗方面，无KRAS突变的A亚型患者的无进展生存率(PFS)好于KRAS突变的患者(P=0.047)。B亚型无KRAS突变的患者与KRAS突变患者的PFS相似(P=0.55)。在验证集中也观察到了类似的结果。我们发现，基因表达谱可以将结直肠癌患者分为四个亚组。抗EGFR治疗的疗效与PCa组分1相关。这项综合性研究可能解释不能切除的晚期或复发结直肠癌的异质性，并可能有助于为结直肠癌治疗寻找新的生物标记物。
Comprehensive gene-expression analysis is very useful for classifying specific cancers into subgroups on the basis of their biological characteristics; it is used both prognostically and predictively. The purpose of this study was to classify unresectable advanced or recurrent colorectal cancer (CRC) by gene-expression profiling of formalin-fixed paraffin-embedded tissues and to correlate CRC subgroups with clinicopathological and molecular features and clinical outcomes.One hundred patients with advanced or recurrent CRC were enrolled. RNA extracted from FFPE tissues was subjected to gene-expression microarray analysis.The patients were stratified into four subgroups (subtypes A1, A2, B1, and B2) by unsupervised hierarchical clustering. By use of principle-components analysis (PCA), the patients were divided into subtypes A and B on the basis of component 1 and into subtypes 1 and 2 on the basis of component 2. Subtype A was significantly enriched among patients without the KRAS mutation and with an earlier clinical stage at diagnosis. With regard to anti-EGFR therapy, progression-free survival (PFS) was better for patients in subtype A without the KRAS mutation than for those with the KRAS mutation (P = 0.047). PFS for patients without the KRAS mutation in subtype B was comparable with that for patients with the KRAS mutation (P = 0.55). Similar results were observed in a validation set.We found that gene-expression profiles enabled stratification of CRC patients into four subgroups. The efficacy of anti-EGFR therapy was correlated with component 1 from PCA. This comprehensive study may explain the heterogeneity of unresectable advanced or recurrent CRC and could be useful for identifying novel biomarkers for CRC treatment.