癌症是不能愈合的伤口:肾再生/修复和肾细胞癌的异同

摘要

癌症被描述为不愈合的伤口,这表明这两种疾病有共同的特征。

通过对肾细胞癌(RCC)中报告的基因表达和肾再生和修复(RRR模型的微阵列数据进行比较,我们研究了这两个过程是否具有相同的分子特征和调节机制。

肾再生和修复和肾细胞癌中表达的基因多数(77%)是一致的,而只有23%的基因是不一致的。改变方向相反)。协调的再生过程,包括细胞增殖和免疫反应,反映在整合基因中。不一致的基因签名揭示了过程(如形态发生和糖酵解)和途径(如缺氧诱导因子和胰岛素样生长因子),反映了肾细胞癌的内在病理性质。这是第一个比较肾细胞癌肾再生和修复基因表达模式的研究。特别是,它与肾细胞癌类似于肾再生与修复中的伤口愈合过程的假设有关。然而,仔细地注意在不一致的方向上调节的基因,为肾癌发生和伤口愈合之间的关键区别提供了新的见解。

这里的观察报告为进一步了解生物学和发展更有效的诊断生物标记和治疗肾肿瘤和肾缺血的治疗方法提供了一个概念性的框架。(癌症Res 2006;66(14):7216 - 24)

参考文献

Cancers as Wounds that Do Not Heal: Differences and Similarities between Renal Regeneration/Repair and Renal Cell Carcinoma

Joseph Riss, Chand Khanna, Seongjoon Koo, Gadisetti V.R. Chandramouli, Howard H. Yang, Ying Hu, David E. Kleiner, Andreas Rosenwald, Carl F. Schaefer, Shmuel A. Ben-Sasson, Liming Yang, John Powell, David W. Kane, Robert A. Star, Olga Aprelikova, Kristin Bauer, James R. Vasselli, Jodi K. Maranchie, Kurt W. Kohn, Ken H. Buetow, W. Marston Linehan, John N. Weinstein, Maxwell P. Lee, Richard D. Klausner and J. Carl Barrett

DOI: 10.1158/0008-5472.CAN-06-0040 Published July 2006

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Abstract

Cancers have been described as wounds that do not heal, suggesting that the two share common features. By comparing microarray data from a model of renal regeneration and repair (RRR) with reported gene expression in renal cell carcinoma (RCC), we asked whether those two processes do, in fact, share molecular features and regulatory mechanisms. The majority (77%) of the genes expressed in RRR and RCC were concordantly regulated, whereas only 23% were discordant (i.e., changed in opposite directions). The orchestrated processes of regeneration, involving cell proliferation and immune response, were reflected in the concordant genes. The discordant gene signature revealed processes (e.g., morphogenesis and glycolysis) and pathways (e.g., hypoxia-inducible factor and insulin-like growth factor-I) that reflect the intrinsic pathologic nature of RCC. This is the first study that compares gene expression patterns in RCC and RRR. It does so, in particular, with relation to the hypothesis that RCC resembles the wound healing processes seen in RRR. However, careful attention to the genes that are regulated in the discordant direction provides new insights into the critical differences between renal carcinogenesis and wound healing. The observations reported here provide a conceptual framework for further efforts to understand the biology and to develop more effective diagnostic biomarkers and therapeutic strategies for renal tumors and renal ischemia. (Cancer Res 2006; 66(14): 7216-24)

Cancers as Wounds that Do Not Heal: Differences and Similarities between Renal Regeneration/Repair and Renal Cell Carcinoma | Cancer Research  http://cancerres.aacrjournals.org/content/66/14/7216