Integrative bioinformatics analysis for identifying the mitochondrial-related gene signature associated with immune infiltration in premature ovarian insufficiency

• Published in: BMC medicine Vol. 22; no. 1; pp. 444 - 22
• Main Authors: Lu, Minjun, Li, Wenxin, Zhou, Jiamin, Shang, Junyu, Lin, Li, Liu, Yueqin, Zhu, Xiaolan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08.10.2024; BioMed Central; BMC
• Subjects: Amodiaquine; Bioaccumulation; Bioinformatics; Bioinformatics analysis; Biomarkers; Cefotaxime; Computational biology; Computational Biology - methods; Correlation analysis; Datasets; Diagnosis; Female; Follicles; Gene expression; Gene Expression Profiling; Gene sequencing; Genes; Genetic aspects; Genomics; Granulosa cells; Health aspects; Humans; Immune cell infiltration; Immune response; Immune system; Immunosuppressive agents; Infertility, Female; Macrophages; Metabolic pathways; Metabolism; Mitochondria; Mitochondria - genetics; Mitochondrial DNA; Mitochondrial dysfunction; Mitophagy; Monocytes; Ovarian diseases; Ovaries; Pharmacology; Premature ovarian insufficiency; Primary Ovarian Insufficiency - genetics; Primary Ovarian Insufficiency - immunology; Protein Interaction Maps - genetics; Protein-protein interactions; Proteins; Reproductive disorders; Reproductive status; RNA; RNA sequencing; Sequence analysis; Theca; Transcriptome; Transcriptomics; China; Bioinformatics analysis; Immune cell infiltration; Mitochondrial dysfunction; Premature ovarian insufficiency
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-024-03675-7

Premature ovarian insufficiency (POI) is a reproductive disorder characterized by the cessation of ovarian function before the age of 40. Although mitochondrial dysfunction and immune disorders are believed to contribute to ovarian damage in POI, the interplay between these factors remains understudied. In this research, transcriptomic data related to POI were obtained from the NCBI GEO database. Hub biomarkers were identified through the construction of a protein‒protein interaction (PPI) network and further validated using RT‒qPCR and Western blot. Moreover, their expression across various cell types was elucidated via single-cell RNA sequencing analysis. A comprehensive investigation of the mitochondrial and immune profiles of POI was carried out through correlation analysis. Furthermore, potential therapeutic agents were predicted utilizing the cMap database. A total of 119 mitochondria-related differentially expressed genes (MitoDEGs) were identified and shown to be significantly enriched in metabolic pathways. Among these genes, Hadhb, Cpt1a, Mrpl12, and Mrps7 were confirmed both in a POI model and in human granulosa cells (GCs), where they were found to accumulate in GCs and theca cells. Immune analysis revealed variations in macrophages, monocytes, and 15 other immune cell types between the POI and control groups. Notably, strong correlations were observed between seven hub-MitoDEGs (Hadhb, Cpt1a, Cpt2, Mrpl12, Mrps7, Mrpl51, and Eci1) and various functions, such as mitochondrial respiratory complexes, dynamics, mitophagy, mitochondrial metabolism, immune-related genes, and immunocytes. Additionally, nine potential drugs (calyculin, amodiaquine, eudesmic acid, cefotaxime, BX-912, prostratin, SCH-79797, HU-211, and pizotifen) targeting key genes were identified. Our results highlight the crosstalk between mitochondrial function and the immune response in the development of POI. The identification of MitoDEGs could lead to reliable biomarkers for the early diagnosis, monitoring, and personalized treatment of POI.