Exosomal miRNA Profiling is a Potential Screening Route for Non-Functional Pituitary Adenoma

Liang Lyu; Haiyan Li; Cheng Chen; Yang Yu; Li Wang; Senlin Yin; Yu Hu; Shu Jiang; Feng Ye; Peizhi Zhou

doi:10.3389/fcell.2021.771354

Exosomal miRNA Profiling is a Potential Screening Route for Non-Functional Pituitary Adenoma

Front Cell Dev Biol. 2022 Jan 18:9:771354. doi: 10.3389/fcell.2021.771354. eCollection 2021.

Authors

Liang Lyu¹, Haiyan Li¹, Cheng Chen¹, Yang Yu¹, Li Wang², Senlin Yin¹, Yu Hu¹, Shu Jiang¹, Feng Ye³, Peizhi Zhou¹

Affiliations

¹ Department of Neurosurgery, Pituitary Adenoma Multidisciplinary Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital of Sichuan University, Chengdu, China.
² Laboratory of Lung Cancer, Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, China.
³ Department of Neurosurgery, People's Hospital of Deyang City, Deyang, China.

Abstract

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.

Keywords: disease screening; exosome; hsa-miR-486-5p; miRNA profile; non-functional pituitary adenoma; progression; relapse.