Gene expression signatures for colorectal cancer microsatellite status and HNPCC.
Gene expression signatures for colorectal cancer microsatellite status and HNPCC.
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DOI：
10.1038/sj.bjc.6602621
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发表时间：
2005-06-20
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
大多数微卫星不稳定 (MSI) 结直肠癌是散发性的，但其中一部分属于遗传性非息肉病性结直肠癌 (HNPCC) 综合征。微卫星不稳定性是由错配修复 (MMR) 系统功能障碍引起的，导致突变表型，MSI 与预后和化疗反应相关。基因表达特征作为许多癌症的预测标记正在开发中，并且 MMR 缺陷特征的识别将在临床和生物学上引起人们的兴趣。为了解决这个问题，我们使用高密度寡核苷酸微阵列分析了 101 种 II 期和 III 期结直肠癌（34 种 MSI，67 种微卫星稳定 (MSS)）的基因表达。根据这些数据，我们构建了一个九基因特征，能够区分错配修复良好和缺陷的肿瘤。随后，我们通过将其转移到实时 RT-PCR 平台来证明签名的稳健性。使用该平台，在由 47 个肿瘤（10 个 MSI，37 个 MSS）组成的独立测试集上验证了签名，其中 45 个肿瘤被正确分类。第二步，我们构建了一个能够将 MMR 缺陷肿瘤分为散发性 MSI 和 HNPCC 病例的特征，并通过数学交叉验证方法对其进行了验证。这种两步分类方法可以识别 MSI 以及 HNPCC 病例的证明值得进一步的基因表达研究，以确定预后特征。
The majority of microsatellite instable (MSI) colorectal cancers are sporadic, but a subset belongs to the syndrome hereditary nonpolyposis colorectal cancer (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch repair (MMR) system that leads to a mutator phenotype, and MSI is correlated to prognosis and response to chemotherapy. Gene expression signatures as predictive markers are being developed for many cancers, and the identification of a signature for MMR deficiency would be of interest both clinically and biologically. To address this issue, we profiled the gene expression of 101 stage II and III colorectal cancers (34 MSI, 67 microsatellite stable (MSS)) using high-density oligonucleotide microarrays. From these data, we constructed a nine-gene signature capable of separating the mismatch repair proficient and deficient tumours. Subsequently, we demonstrated the robustness of the signature by transferring it to a real-time RT-PCR platform. Using this platform, the signature was validated on an independent test set consisting of 47 tumours (10 MSI, 37 MSS), of which 45 were correctly classified. In a second step, we constructed a signature capable of separating MMR-deficient tumours into sporadic MSI and HNPCC cases, and validated this by a mathematical cross-validation approach. The demonstration that this two-step classification approach can identify MSI as well as HNPCC cases merits further gene expression studies to identify prognostic signatures.
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影响因子：
37.3
作者：
Banerjea A;Ahmed S;Hands RE;Huang F;Han X;Shaw PM;Feakins R;Bustin SA;Dorudi S
通讯作者：
Dorudi S
影响因子：
158.5
作者：
Ribic, CM;Sargent, DJ;Gallinger, S
通讯作者：
Gallinger, S
影响因子：
6.4
作者：
Cappel, WHDN;Meulenbeld, HJ;Vasen, HFA
通讯作者：
Vasen, HFA
影响因子：
168.9
作者：
Cunningham, D;Pyrhönen, S;Herait, P
通讯作者：
Herait, P
影响因子：
168.9
作者：
Elsaleh, H;Joseph, D;Iacopetta, B
通讯作者：
Iacopetta, B