Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI, 54449, USA.
Hinda and Arthur Marcus Institute for Aging Research at Hebrew Senior Life, Boston, MA, USA.
Sci Rep. 2022 Mar 9;12(1):4141. doi: 10.1038/s41598-022-08082-7.
Bladder urothelial carcinoma (BLC) is one of the most common cancers in men, and its heterogeneity challenges the treatment to cure this disease. Recently, microRNAs (miRNAs) gained promising attention as biomarkers due to their potential roles in cancer biology. Identifying survival-associated miRNAs may help identify targets for therapeutic interventions in BLC. This work aims to identify a miRNA signature that could estimate the survival in patients with BLC. We developed a survival estimation method called BLC-SVR based on support vector regression incorporated with an optimal feature selection algorithm to select a robust set of miRNAs as a signature to estimate the survival in patients with BLC. BLC-SVR identified a miRNA signature consisting of 29 miRNAs and obtained a mean squared correlation coefficient and mean absolute error of 0.79 ± 0.02 and 0.52 ± 0.32 year between actual and estimated survival times, respectively. The prediction performance of BLC-SVR had a better estimation capability than other standard regression methods. In the identified miRNA signature, 14 miRNAs, hsa-miR-432-5p, hsa-let-7e-3p, hsa-miR-652-3p, hsa-miR-629-5p, and hsa-miR-203a-3p, hsa-miR-129-5p, hsa-miR-769-3p, hsa-miR-570-3p, hsa-miR-320c, hsa-miR-642a-5p, hsa-miR-496, hsa-miR-5480-3p, hsa-miR-221-5p, and hsa-miR-7-1-3p, were found to be good biomarkers for BLC diagnosis; and the six miRNAs, hsa-miR-652-5p, hsa-miR-193b-5p, hsa-miR-129-5p, hsa-miR-143-5p, hsa-miR-496, and hsa-miR-7-1-3p, were found to be good biomarkers of prognosis. Further bioinformatics analysis of this miRNA signature demonstrated its importance in various biological pathways and gene ontology annotation. The identified miRNA signature would further help in understanding of BLC diagnosis and prognosis in the development of novel miRNA-target based therapeutics in BLC.
膀胱癌（BLC）是男性最常见的癌症之一，其异质性给治疗这种疾病带来了挑战。最近，microRNAs（miRNAs）作为生物标志物引起了人们的关注，因为它们在癌症生物学中具有潜在的作用。鉴定与生存相关的 miRNAs 可能有助于确定 BLC 治疗干预的靶点。本工作旨在鉴定一个 miRNA 特征，以估计 BLC 患者的生存情况。我们开发了一种称为 BLC-SVR 的生存估计方法，该方法基于支持向量回归，结合了最优特征选择算法，以选择一组稳健的 miRNAs 作为特征，以估计 BLC 患者的生存情况。BLC-SVR 确定了一个由 29 个 miRNAs 组成的 miRNA 特征，实际生存时间和估计生存时间之间的均方相关系数和平均绝对误差分别为 0.79 ± 0.02 和 0.52 ± 0.32 年。BLC-SVR 的预测性能具有更好的估计能力，优于其他标准回归方法。在鉴定的 miRNA 特征中，有 14 个 miRNAs（hsa-miR-432-5p、hsa-let-7e-3p、hsa-miR-652-3p、hsa-miR-629-5p 和 hsa-miR-203a-3p、hsa-miR-129-5p、hsa-miR-769-3p、hsa-miR-570-3p、hsa-miR-320c、hsa-miR-642a-5p、hsa-miR-496、hsa-miR-5480-3p、hsa-miR-221-5p 和 hsa-miR-7-1-3p）被发现是 BLC 诊断的良好生物标志物；而 hsa-miR-652-5p、hsa-miR-193b-5p、hsa-miR-129-5p、hsa-miR-143-5p、hsa-miR-496 和 hsa-miR-7-1-3p 这 6 个 miRNAs 被发现是预后的良好生物标志物。对这个 miRNA 特征的进一步生物信息学分析表明，它在各种生物学途径和基因本体注释中具有重要作用。鉴定的 miRNA 特征将有助于进一步了解 BLC 的诊断和预后，为基于 miRNA 靶点的治疗方法在 BLC 中的开发提供帮助。
