Differential expression of prognostic proteomic markers in primary tumour, venous tumour thrombus and metastatic renal cell cancer tissue and correlation with patient outcome.
Differential expression of prognostic proteomic markers in primary tumour, venous tumour thrombus and metastatic renal cell cancer tissue and correlation with patient outcome.
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DOI：
10.1371/journal.pone.0060483
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Stewart GD
中科院分区：
文献类型：
--
作者：
Laird A;O'Mahony FC;Nanda J;Riddick AC;O'Donnell M;Harrison DJ;Stewart GD
肾细胞癌（RCC）是最致命的泌尿系统恶性肿瘤。三分之一的患者在诊断时患有转移性疾病，另外三分之一的患者在摘除手术后出现转移性疾病。尽管在风险分层中常规使用预后临床病理参数，但临床过程中的异质性使得预测转移非常困难。随着对疾病发病机制的深入了解，许多生物标志物已被证明具有预后意义，包括 Ki67、p53、血管内皮生长因子受体 1 (VEGFR1) 和配体 D (VEGFD)、SNAIL 和 SLUG。之前的通路分析主要来自于原发性肿瘤的研究，很少关注作为靶向分子治疗重点的转移性肿瘤。因此，在本研究中，创建了来自 177 名原发性肾肿瘤、肾静脉肿瘤血栓和/或肾细胞癌转移患者的组织微阵列，并与免疫荧光自动定量分析 (AQUA) 一起使用，以研究这些标记物在局部晚期和转移性疾病中的预后意义。此外，这使得可以评估原发肿瘤、肾静脉肿瘤血栓和转移瘤之间的差异蛋白表达。结果表明，临床病理参数仍然是癌症特异性生存最重要的预测因素。然而，在局部晚期和转移性疾病的单变量分析中，高 VEGFR1 或 VEGFD 可以预测较差的癌症特异性生存率。转移灶中Ki67、p53、VEGFR1、SLUG、SNAIL的表达量显着高于原发灶和肾静脉癌栓。除 p53 外，这些蛋白质表达差异此前并未在 RCC 中表现出来。这证实了增殖、血管生成和上皮间质转化在肾细胞癌发病机制和转移中的重要性。重要的是，这项工作强调需要对转移性肿瘤进行进一步的通路分析，以克服耐药性并开发新疗法。
Renal cell carcinoma (RCC) is the most deadly of urological malignancies. Metastatic disease affects one third of patients at diagnosis with a further third developing metastatic disease after extirpative surgery. Heterogeneity in the clinical course ensures predicting metastasis is notoriously difficult, despite the routine use of prognostic clinico-pathological parameters in risk stratification. With greater understanding of pathways involved in disease pathogenesis, a number of biomarkers have been shown to have prognostic significance, including Ki67, p53, vascular endothelial growth factor receptor 1 (VEGFR1) and ligand D (VEGFD), SNAIL and SLUG. Previous pathway analysis has been from study of the primary tumour, with little attention to the metastatic tumours which are the focus of targeted molecular therapies. As such, in this study a tissue microarray from 177 patients with primary renal tumour, renal vein tumour thrombus and/or RCC metastasis has been created and used with Automated Quantitative Analysis (AQUA) of immunofluorescence to study the prognostic significance of these markers in locally advanced and metastatic disease. Furthermore, this has allowed assessment of differential protein expression between the primary tumours, renal vein tumour thrombi and metastases. The results demonstrate that clinico-pathological parameters remain the most significant predictors of cancer specific survival; however, high VEGFR1 or VEGFD can predict poor cancer specific survival on univariate analysis for locally advanced and metastatic disease. There was significantly greater expression of Ki67, p53, VEGFR1, SLUG and SNAIL in the metastases compared with the primary tumours and renal vein tumour thrombi. With the exception of p53, these differences in protein expression have not been shown previously in RCC. This confirms the importance of proliferation, angiogenesis and epithelial to mesenchymal transition in the pathogenesis and metastasis of RCC. Importantly, this work highlights the need for further pathway analysis of metastatic tumours for overcoming drug resistance and developing new therapies.
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影响因子：
3.8
作者：
D'Andrea, Mario R.;Limiti, Maria R.;Mingazzini, Pietro L.
通讯作者：
Mingazzini, Pietro L.
影响因子：
4
作者：
Ganepola, Ganepola A. P.;Mazziotta, Robert M.;Mariadason, John M.
通讯作者：
Mariadason, John M.
影响因子：
4.5
作者：
Jacobsen, J;Grankvist, K;Ljungberg, B
通讯作者：
Ljungberg, B
影响因子：
2
作者：
Dirim, Ayhan;Haberal, Asuman Nihan;Ozkardes, Hakan
通讯作者：
Ozkardes, Hakan
DOI：
10.1056/nejmoa1113205
发表时间：
2012-03-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Gerlinger M;Rowan AJ;Horswell S;Math M;Larkin J;Endesfelder D;Gronroos E;Martinez P;Matthews N;Stewart A;Tarpey P;Varela I;Phillimore B;Begum S;McDonald NQ;Butler A;Jones D;Raine K;Latimer C;Santos CR;Nohadani M;Eklund AC;Spencer-Dene B;Clark G;Pickering L;Stamp G;Gore M;Szallasi Z;Downward J;Futreal PA;Swanton C
通讯作者：
Swanton C