Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds.
Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds.
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DOI：
10.1371/journal.pbio.0020007
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发表时间：
2004-02
期刊：
影响因子：
9.8
通讯作者：
Brown PO
中科院分区：
文献类型：
--
作者：
Chang HY;Sneddon JB;Alizadeh AA;Sood R;West RB;Montgomery K;Chi JT;van de Rijn M;Botstein D;Brown PO
癌症的侵袭和转移被比作伤口愈合出了问题。尽管癌症进展和伤口愈合之间的细胞行为相似，但这两个过程之间的分子关系及其预后意义尚不清楚。在这项研究中，基于来自10个解剖部位的成纤维细胞的基因表达谱，我们确定了一个针对血清暴露的刻板基因表达程序，似乎反映了成纤维细胞在伤口愈合中的多方面作用。构成这种成纤维细胞共同血清反应的基因在许多人类肿瘤中受到协调调节，使我们能够识别具有提示创面活动的基因表达特征的肿瘤。在成纤维细胞血清反应程序中诱导的基因在肿瘤中由肿瘤细胞本身表达，由肿瘤相关成纤维细胞表达，或两者兼而有之。定义这种伤口样表型的分子特征在早期临床阶段就很明显，在治疗过程中持续存在，并预测乳腺癌、肺癌和胃癌转移和死亡的风险增加。因此，成纤维细胞对血清的反应的转录特征提供了癌症进展和伤口愈合之间的可能联系，也是几种常见癌症临床病程的有力预测因子。成纤维细胞对血清反应的转录特征提供了癌症进展和伤口愈合之间的可能联系，也是几种常见癌症的临床病程的预测因子。
Cancer invasion and metastasis have been likened to wound healing gone awry. Despite parallels in cellular behavior between cancer progression and wound healing, the molecular relationships between these two processes and their prognostic implications are unclear. In this study, based on gene expression profiles of fibroblasts from ten anatomic sites, we identify a stereotyped gene expression program in response to serum exposure that appears to reflect the multifaceted role of fibroblasts in wound healing. The genes comprising this fibroblast common serum response are coordinately regulated in many human tumors, allowing us to identify tumors with gene expression signatures suggestive of active wounds. Genes induced in the fibroblast serum-response program are expressed in tumors by the tumor cells themselves, by tumor-associated fibroblasts, or both. The molecular features that define this wound-like phenotype are evident at an early clinical stage, persist during treatment, and predict increased risk of metastasis and death in breast, lung, and gastric carcinomas. Thus, the transcriptional signature of the response of fibroblasts to serum provides a possible link between cancer progression and wound healing, as well as a powerful predictor of the clinical course in several common carcinomas. The transcriptional signature of the response of fibroblasts to serum provides a possible link between cancer progression and wound healing, as well as a predictor of the clinical course in several common cancers
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影响因子：
56.9
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