Biomedica Molecular Medicine SL, Madrid, Spain.
Urology Service, Hospital Universitario 12 de Octubre, Madrid, Spain.
PLoS One. 2020 Feb 28;15(2):e0229075. doi: 10.1371/journal.pone.0229075. eCollection 2020.
Renal cell carcinoma comprises a variety of entities, the most common being the clear-cell, papillary and chromophobe subtypes. These subtypes are related to different clinical evolution; however, most therapies have been developed for clear-cell carcinoma and there is not a specific treatment based on different subtypes. In this study, one hundred and sixty-four paraffin samples from primary nephrectomies for localized tumors were analyzed. MiRNAs were isolated and measured by microRNA arrays. Significance Analysis of Microarrays and Consensus Cluster algorithm were used to characterize different renal subtypes. The analyses showed that chromophobe renal tumors are a homogeneous group characterized by an overexpression of miR 1229, miR 10a, miR 182, miR 1208, miR 222, miR 221, miR 891b, miR 629-5p and miR 221-5p. On the other hand, clear cell renal carcinomas presented two different groups inside this histological subtype, with differences in miRNAs that regulate focal adhesion, transcription, apoptosis and angiogenesis processes. Specifically, one of the defined groups had an overexpression of proangiogenic microRNAs miR185, miR126 and miR130a. In conclusion, differences in miRNA expression profiles between histological renal subtypes were established. In addition, clear cell renal carcinomas had different expression of proangiogenic miRNAs. With the emergence of antiangiogenic drugs, these differences could be used as therapeutic targets in the future or as a selection method for tailoring personalized treatments.
肾细胞癌包括多种实体瘤,最常见的是透明细胞癌、乳头状癌和嫌色细胞癌亚型。这些亚型与不同的临床演变有关;然而,大多数治疗方法都是针对透明细胞癌开发的,并没有针对不同亚型的特定治疗方法。在这项研究中,分析了 164 例局部肿瘤行肾切除术的石蜡样本。通过 microRNA 芯片分离并测量 microRNAs。采用差异表达分析和共识聚类算法来描述不同的肾亚型。分析表明,嫌色细胞肾肿瘤是一个同质群体,其特征是 miR 1229、miR 10a、miR 182、miR 1208、miR 222、miR 221、miR 891b、miR 629-5p 和 miR 221-5p 的过表达。另一方面,透明细胞肾细胞癌在这个组织学亚型内呈现出两个不同的群体,其 miRNA 调节焦点粘附、转录、凋亡和血管生成过程存在差异。具体来说,定义的一个组中过表达了促血管生成的 microRNAs miR185、miR126 和 miR130a。总之,建立了组织学肾亚型之间 microRNA 表达谱的差异。此外,透明细胞肾细胞癌有不同的促血管生成 microRNAs 表达。随着抗血管生成药物的出现,这些差异将来可以作为治疗靶点,或作为制定个体化治疗方案的选择方法。