A gene expression signature for chemoradiosensitivity of colorectal cancer cells.
A gene expression signature for chemoradiosensitivity of colorectal cancer cells.
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DOI：
10.1016/j.ijrobp.2010.06.023
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发表时间：
2010-11-15
期刊：
影响因子：
--
通讯作者：
Grade M
中科院分区：
文献类型：
--
作者：
Spitzner M;Emons G;Kramer F;Gaedcke J;Rave-Fränk M;Scharf JG;Burfeind P;Becker H;Beissbarth T;Ghadimi BM;Ried T;Grade M
局部晚期直肠癌患者的标准治疗包括术前5-氟尿嘧啶为主的放化疗，然后进行标准化手术。然而，肿瘤对多模式治疗的反应差异很大，从完全耐药到完全病理消退。因此，对反应的预测是重要的临床需求。为了建立研究这种异质性肿瘤反应的分子基础的体外模型，我们将12个结直肠癌细胞系暴露于3 μM的5-氟尿嘧啶和2戈伊的辐射。然后将治疗敏感性的差异与这些细胞系的治疗前基因表达谱相关。我们观察到了异质性反应，存活分数范围为0.28至0.81，密切概括了临床现实。使用线性模型分析，我们确定了4，796个特征，其表达水平与放化疗敏感性显著相关（Q <0.05），包括许多参与丝裂原活化蛋白激酶信号通路或细胞周期基因的基因。这些数据表明胰岛素和Wnt信号通路与治疗反应的潜在相关性，我们将STAT 3、RASSF 1、DOK 3和ERBB 2确定为潜在的治疗靶点。使用实时聚合酶链反应对这些基因的一个子集的微阵列测量进行独立验证。我们是第一个报告的基因表达签名在体外化疗放射敏感性的结直肠癌细胞。我们预计，这项分析将揭示预测直肠癌对放化疗反应的分子生物标志物，并能够鉴定可作为靶点的基因，以使先验耐药的原发性肿瘤敏感。
The standard treatment of patients with locally advanced rectal cancers comprises preoperative 5-fluorouracil-based chemoradiotherapy followed by standardized surgery. However, tumor response to multimodal treatment has varied greatly, ranging from complete resistance to complete pathologic regression. The prediction of the response is, therefore, an important clinical need. To establish in vitro models for studying the molecular basis of this heterogeneous tumor response, we exposed 12 colorectal cancer cell lines to 3 μM of 5-fluorouracil and 2 Gy of radiation. The differences in treatment sensitivity were then correlated with the pretherapeutic gene expression profiles of these cell lines. We observed a heterogeneous response, with surviving fractions ranging from 0.28 to 0.81, closely recapitulating clinical reality. Using a linear model analysis, we identified 4,796 features whose expression levels correlated significantly with the sensitivity to chemoradiotherapy (Q <.05), including many genes involved in the mitogen-activated protein kinase signaling pathway or cell cycle genes. These data have suggested a potential relevance of the insulin and Wnt signaling pathways for treatment response, and we identified STAT3, RASSF1, DOK3, and ERBB2 as potential therapeutic targets. The microarray measurements were independently validated for a subset of these genes using real-time polymerase chain reactions. We are the first to report a gene expression signature for the in vitro chemoradiosensitivity of colorectal cancer cells. We anticipate that this analysis will unveil molecular biomarkers predictive of the response of rectal cancers to chemoradiotherapy and enable the identification of genes that could serve as targets to sensitize a priori resistant primary tumors.
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DOI：
10.1016/s0360-3016(02)04618-7
发表时间：
2003-04-01
影响因子：
7
作者：
Rödel, C;Haas, J;Rödel, F
通讯作者：
Rödel, F
影响因子：
50.3
作者：
Neve, Richard M.;Chin, Koei;Gray, Joe W.
通讯作者：
Gray, Joe W.
影响因子：
2.1
作者：
Honma, M;Higuchi, O;Yamanashi, Y
通讯作者：
Yamanashi, Y
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
11.2
作者：
Amundson, Sally A.;Do, Khanh T.;Fornace, Albert J., Jr.
通讯作者：
Fornace, Albert J., Jr.