Identification of gene signature for treatment response to guide precision oncology in clear-cell renal cell carcinoma
Identification of gene signature for treatment response to guide precision oncology in clear-cell renal cell carcinoma
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DOI：
10.1038/s41598-020-58804-y
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发表时间：
2020-02-06
影响因子：
4.6
通讯作者：
So, Alan I.
中科院分区：
文献类型：
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作者：
D'Costa, Ninadh M.;Cina, Davide;So, Alan I.
肾透明细胞癌(CcRCC)是一种常见的耐药疾病，具有异常的血管生成和免疫抑制特征。转移性疾病的患者根据临床特征进行靶向治疗：低风险患者通常使用抗血管生成药物治疗，中/高风险患者通常使用免疫治疗。然而，目前还没有生物标志物可用于指导这些患者的治疗选择。最近发表的一项II期临床试验观察到ccRCC患者的聚集性与他们对靶向治疗的反应之间的相关性。然而，这些群体的聚集性并不明显。在这里，我们分析了469名ccRCC患者的基因表达谱，使用特征选择技术，并开发了一种改进的66基因签名，用于改进患者的亚型。此外，我们已经确定了一个新的全面的表达谱来区分迁移基质细胞和免疫细胞。此外，所提出的66基因签名被使用不同的慢性肾细胞癌患者队列来验证。这些发现为开发可靠的生物标志物奠定了基础，这些标志物可以指导治疗决策，改善慢性肾细胞癌患者的治疗反应。
Clear-cell renal cell carcinoma (ccRCC) is a common therapy resistant disease with aberrant angiogenic and immunosuppressive features. Patients with metastatic disease are treated with targeted therapies based on clinical features: low-risk patients are usually treated with anti-angiogenic drugs and intermediate/high-risk patients with immune therapy. However, there are no biomarkers available to guide treatment choice for these patients. A recently published phase II clinical trial observed a correlation between ccRCC patients' clustering and their response to targeted therapy. However, the clustering of these groups was not distinct. Here, we analyzed the gene expression profile of 469 ccRCC patients, using featured selection technique, and have developed a refined 66-gene signature for improved sub-classification of patients. Moreover, we have identified a novel comprehensive expression profile to distinguish between migratory stromal and immune cells. Furthermore, the proposed 66-gene signature was validated using a different cohort of 64 ccRCC patients. These findings are foundational for the development of reliable biomarkers that may guide treatment decision-making and improve therapy response in ccRCC patients.