Angiogenesis Pathway in Kidney Renal Clear Cell Carcinoma and Its Prognostic Value for Cancer Risk Prediction.
Angiogenesis Pathway in Kidney Renal Clear Cell Carcinoma and Its Prognostic Value for Cancer Risk Prediction.
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DOI：
10.3389/fmed.2021.731214
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发表时间：
2021
影响因子：
3.9
通讯作者：
Wu G
中科院分区：
文献类型：
--
作者：
Che X;Su W;Li X;Liu N;Wang Q;Wu G
血管生成是一个受促血管生成因子和抗血管生成因子高度调控的过程，在癌症中受到干扰和失调。尽管血管生成抑制剂在癌症治疗中的临床应用越来越多，但大多数分子靶向药物的效果不如预期。因此，有必要对血管生成途径进行深入探讨。本研究利用癌症基因组图谱数据库研究了血管生成相关基因在多种肿瘤中的表达，发现其中大部分是肾透明细胞癌(KIRC)患者的保护性基因。我们根据这些基因的mRNA表达水平将来自KIRC数据集中的样本分为三类，浓缩分数的顺序是：第二类(上调表达)>；第三类(正常表达)>；第一类(下调表达)。绘制的三个组的生存曲线显示，组2的患者总体存活率最高。通过对癌症药物敏感性基因组数据库中所列药物的敏感性分析，我们生成了三个簇中12种常用的KIRC分子靶向药物的IC50估计，可以根据血管生成相关基因的表达为患者提供更个性化的治疗方案。随后，我们研究了血管生成途径与经典肿瘤相关基因的相关性，以及血管生成评分与免疫细胞浸润的相关性。最后，我们使用最小绝对收缩和选择算子(LASSO)-COX回归分析来构建预测KIRC患者生存的风险评分模型。根据受试者工作特征(ROC)曲线下面积，这种基于血管生成相关基因的新生存模型具有较高的预后预测价值。我们的研究结果将为KIRC患者的临床诊断和治疗提供新的途径。
Angiogenesis, a process highly regulated by pro-angiogenic and anti-angiogenic factors, is disrupted and dysregulated in cancer. Despite the increased clinical use of angiogenesis inhibitors in cancer therapy, most molecularly targeted drugs have been less effective than expected. Therefore, an in-depth exploration of the angiogenesis pathway is warranted. In this study, the expression of angiogenesis-related genes in various cancers was explored using The Cancer Genome Atlas datasets, whereupon it was found that most of them were protective genes in the patients with kidney renal clear cell carcinoma (KIRC). We divided the samples from the KIRC dataset into three clusters according to the mRNA expression levels of these genes, with the enrichment scores being in the order of Cluster 2 (upregulated expression) > Cluster 3 (normal expression) > Cluster 1 (downregulated expression). The survival curves plotted for the three clusters revealed that the patients in Cluster 2 had the highest overall survival rates. Via a sensitivity analysis of the drugs listed on the Genomics of Drug Sensitivity in Cancer database, we generated IC50 estimates for 12 commonly used molecularly targeted drugs for KIRC in the three clusters, which can provide a more personalized treatment plan for the patients according to angiogenesis-related gene expression. Subsequently, we investigated the correlation between the angiogenesis pathway and classical cancer-related genes as well as that between the angiogenesis score and immune cell infiltration. Finally, we used the least absolute shrinkage and selection operator (LASSO)–Cox regression analysis to construct a risk score model for predicting the survival of patients with KIRC. According to the areas under the receiver operating characteristic (ROC) curves, this new survival model based on the angiogenesis-related genes had high prognostic prediction value. Our results should provide new avenues for the clinical diagnosis and treatment of patients with KIRC.
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影响因子：
8.8
作者：
Jenkins RW;Barbie DA;Flaherty KT
通讯作者：
Flaherty KT
影响因子：
64.5
作者：
Binnewies, Mikhail;Mujal, Adriana M.;Krummel, Matthew F.
通讯作者：
Krummel, Matthew F.
DOI：
10.1016/j.urolonc.2017.08.016
发表时间：
2017-12-01
影响因子：
2.7
作者：
Jeh, Seong Uk;Park, Jung Je;Hwa, Jeong Seok
通讯作者：
Hwa, Jeong Seok
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
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