MicroRNA Profiling in Wilms Tumor: Identification of Potential Biomarkers

Frontiers in Pediatrics

article

Fabiola Jimena Pérez-Linares¹  Pilar Eguía-Aguilar¹  Mario Pérezpeña-Diazconti³  Jorge García-Quintana¹  Guillermina Baay-Guzmán¹  Lourdes Cabrera-Muñoz¹  Stanislaw Sadowinski-Pine¹  Carlos Serrano-Bello¹  Marco Murillo-Maldonado¹  Alejandra Contreras-Ramos⁴ 

[1] Laboratorio de Biología Molecular, Departamento de Patología Clínica y Experimental, Hospital Infantil de México Federico Gómez;Universidad Nacional Autónoma de México;Instituto de Oftalmología Conde de Valenciana;Laboratorio de Biología del Desarrollo y Teratogénesis Experimental, Hospital Infantil de México Federico Gómez

关键词: anaplasia;    microRNA;    triphasic;    Wilms tumor;    TLDA;    in situ hybridization;    RT-qPCR;   

DOI  :  10.3389/fped.2020.00337

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Wilms tumor (WT) is the most frequently diagnosed malignant renal tumor in children. With current treatments, ~90% of children diagnosed with WT survive and generally present with tumors characterized by favorable histology (FHWT), whereas prognosis is poor for the remaining 10% of cases where the tumors are characterized by cellular diffuse anaplasia (DAWT). Relatively few studies have investigated microRNA-related epigenetic regulation and its relationship with altered gene expression in WT. Here, we aim to identify microRNAs differentially expressed in WT and describe their expression in terms of cellular anaplasia, metastasis, and association with the main genetic alterations in WT to identify potential prognostic biomarkers. Expression profiling using TaqMan low-density array was performed in a discovery cohort consisting of four DAWT and eight FHWT samples. Relative quantification resulted in the identification of 109 (48.7%) microRNAs differentially expressed in both WT types. Of these, miR-10a-5p, miR-29a-3p, miR-181a-5p, miR-200b-3p, and miR-218-5p were selected and tested by RT-qPCR on a validation cohort of 53 patient samples. MiR-29a and miR-218 showed significant differences in FHWT with low ( P = 0.0018) and high ( P = 0.0131) expression, respectively. To discriminate between miRNA expression FHWTs and healthy controls, the receiver operating characteristic (ROC) curves were obtained; miR-29a AUC was 0.7843. Furthermore, low expression levels of miR-29a and miR-200b ( P = 0.0027 and P = 0.0248) were observed in metastatic tumors. ROC curves for miR-29a discriminated metastatic patients (AUC = 0.8529) and miR-200b (AUC = 0.7757). To confirm the differences between cases with poor prognosis, we performed in situ hybridization for three microRNAs in five DAWT and 17 FHWT samples, and only significant differences between adjacent tissues and FHWT tumors were found for miR-181a, miR-200b, and miR-218, in both total pixels and nuclear analyses. Analysis of copy number variation in genes showed that the most prevalent alterations were WTX (47%), IGF2 (21%), 1q (36%) gain, 1p36 (16%), and WTX deletion/1q duplicate (26%). The five microRNAs evaluated are involved in the Hippo signaling pathway and participate in Wilms tumor development through their effects on differentiation, proliferation, angiogenesis, and metastasis.

【 授权许可】

CC BY