期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.771354
关键词
non-functional pituitary adenoma; exosome; miRNA profile; hsa-miR-486-5p; disease screening; progression; relapse
资金
- Foundation of Science and Technology Department of Sichuan province [22ZDYF1276, 2016SZ0015, 2019YFS0395]
- Health Commission of Sichuan province [20PJ247]
- Sichuan Medical Association [S18072]
- 1.3.5 project for disciplines of excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University [2019HXFH018]
- National Natural Science Foundation of China [81802096]
- Post-Doctor Research Project, West China Hospital, Sichuan University [2020HXBH15]
This study developed a method for screening and prognostic prediction of NFPAs using serum exosomal miRNA profiles. The researchers found that hsa-miR-486-5p, hsa-miR-151a-5p, hsa-miR-652-3p_R+1, and hsa-miR-1180-3p could be potential biomarkers for NFPA diagnosis and screening, with hsa-miR-486-5p being the most promising one. Furthermore, exosomal hsa-miR-486-5p was found to be an efficient predictive biomarker for NFPAs progression or relapse.
Non-functional pituitary adenomas (NFPAs) are one of the most prevalent pituitary adenoma subtypes. The lack of reliable screening approach for NFPAs for the insidious clinical course usually leads to delays in medical therapy and consequently worse prognosis. Hence, we employed a sequence cohort (patient: control, 6:2) and a validation cohort (patient: control, 22:8) to develop a serum exosomal miRNA profile-based method for NFPA screening and prognosis prediction. We found that a total of 1,395 kinds of human miRNA were detected. Compared with healthy donors, 18 up-regulated and 36 down-regulated miRNAs showed significant expression alterations in NFPA patients. Target genes of differentially expressed miRNAs are mainly enriched in axonogenesis and cancer-associated terms. After validation, hsa-miR-486-5p, hsa-miR-151a-5p, hsa-miR-652-3p_R+1, and hsa-miR-1180-3p were promising biomarkers for NFPA, in which miR-486-5p was the most competent one. After a median of 33 months of prospective follow-up, exosomal hsa-miR-486-5p also was an efficient predictive biomarker for progression or relapse of NFPAs. By protein-protein interaction network construction of hsa-miR-486-5p targeted genes, the core modules revealed a high possibility that exosomal hsa-miR-486-5p regulated tumor progression by epigenetic regulation of MAPK signaling pathways. In conclusion, exosomal hsa-miR-486-5p, hsa-miR-151a-5p, hsa-miR-652-3p_R+1, and hsa-miR-1180-3p are candidate biomarkers for diagnosis and screening of NFPAs. More importantly, prospective follow-up reveals that hsa-miR-486-5p can be regarded as a significant predictor for prognosis of NFPAs.
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