Identification of MicroRNAs as Potential Biomarkers in Ovarian Endometriosis

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This study identified 114 differentially expressed miRNAs in ovarian endometriosis plasma, with 14 downregulated miRNAs, including hsa-let-7i-5p, showing diagnostic potential.

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The paper studied microRNA (miRNA) expression profiles in plasma from 10 patients with ovarian endometriosis and 10 healthy controls, using microarray-based profiling of ectopic endometrial plasma followed by RT-qPCR validation. It identified 114 differentially expressed miRNAs, with 14 significantly downregulated in patients, and ROC analysis showed hsa-let-7i-5p had the highest diagnostic performance (AUC = 0.900) among the 14. Predicted target genes of these miRNAs were analyzed for enrichment, with results implicating KEGG pathways such as microRNAs in cancer and endocrine resistance and related GO metabolic processes. The main limitation is the small sample size (10 per group), which may constrain generalizability and robustness of biomarker performance. This paper is centrally about endometriosis — specifically identifying 14 downregulated plasma miRNAs, including hsa-let-7i-5p, as potential biomarkers in ovarian endometriosis.

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Abstract

Endometriosis, as a prevalent gynecological disease, is characterized by the presence of endometrial-like tissue outside the uterus, causing infertility and considerable pain and affecting the quality of life of women. The pathogenic mechanism has not been fully elucidated, and there are no effective biomarkers for endometriosis. In our study, microRNA (miRNA) expression profiling of 10 ectopic endometrial plasma from patients with ovarian endometriosis and 10 normal plasma from healthy controls was analyzed using a microarray. As a result, 114 differentially expressed miRNAs were identified. Among them, 14 miRNAs were significantly downregulated in patients with ovarian endometriosis, which matched the microarray results. The diagnostic value of the 14 downregulated miRNAs in ovarian endometriosis was evaluated by receiver operating characteristic (ROC) curve analysis, and hsa-let-7i-5p showed the highest area under the ROC curve (AUC) with a value of 0.900. The target genes of the 14 miRNAs were predicted by miRWalk2.0, and the genes that were targeted by at least 2 of the 14 miRNAs were analyzed by function enrichment. The target genes were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as microRNAs in cancer, bladder cancer, and endocrine resistance pathways, and the Gene Ontology (GO) terms such as nucleobase-containing compound metabolic process, cellular nitrogen compound biosynthetic process, and heterocycle metabolic process. The identified 14 differentially expressed miRNAs could be potential biomarkers and therapeutic targets for the diagnosis and treatment of endometriosis.
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Abstract

Endometriosis, as a prevalent gynecological disease, is characterized by the presence of endometrial-like tissue outside the uterus, causing infertility and considerable pain and affecting the quality of life of women. The pathogenic mechanism has not been fully elucidated, and there are no effective biomarkers for endometriosis. In our study, microRNA (miRNA) expression profiling of 10 ectopic endometrial plasma from patients with ovarian endometriosis and 10 normal plasma from healthy controls was analyzed using a microarray. As a result, 114 differentially expressed miRNAs were identified. Among them, 14 miRNAs were significantly downregulated in patients with ovarian endometriosis, which matched the microarray results. The diagnostic value of the 14 downregulated miRNAs in ovarian endometriosis was evaluated by receiver operating characteristic (ROC) curve analysis, and hsa-let-7i-5p showed the highest area under the ROC curve (AUC) with a value of 0.900. The target genes of the 14 miRNAs were predicted by miRWalk2.0, and the genes that were targeted by at least 2 of the 14 miRNAs were analyzed by function enrichment. The target genes were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as microRNAs in cancer, bladder cancer, and endocrine resistance pathways, and the Gene Ontology (GO) terms such as nucleobase-containing compound metabolic process, cellular nitrogen compound biosynthetic process, and heterocycle metabolic process. The identified 14 differentially expressed miRNAs could be potential biomarkers and therapeutic targets for the diagnosis and treatment of endometriosis. Similar content being viewed by others

References

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Shen H, Lu S, Dong L, Xue Y, Yao C, Tong C, et al. hsa-miR-320d and hsa-miR-582, miRNA biomarkers of aortic dissection, regulate apoptosis of vascular smooth muscle cells. J Cardiovasc Pharmacol. 2018;71(5):275–82. Funding Grants from National Natural Science Foundation of China: High-throughput sequencing identifying pathogenic genes of endometriosis (Grant No. 81571411). Author information Authors and Affiliations Contributions Chenglei Gu and Zhe Zhang contributed to the conception of the study; Wensheng Fan and Li Lian performed the experiments; Mingxia Ye, Qian Zhang, and Nina Zhang helped for acquisition of data and analysis and interpretation of data; Yuanguang Meng has been involved in drafting the manuscript or revising it critically for important intellectual content; Zhen Li provided valuable instructions and suggestions for this paper and helped for revising the manuscript; all authors have read and approved the final version of the manuscript for publication. Corresponding author Ethics declarations Written informed consent forms were obtained from all participants prior to surgery, and our study was approved by the Ethics Committee of the Chinese PLA General Hospital. Conflict of Interest The authors declare that they have no competing interests. Additional information Highlights •Microarray analysis identified 114 DEmiRNAs in endometriosis patients. •Fourteen miRNAs were validated to be downregulated by RT-qPCR. •The 14 DEmiRNAs may be potential biomarkers for endometriosis. Rights and permissions About this article Cite this article Gu, Cl., Zhang, Z., Fan, Ws. et al. Identification of MicroRNAs as Potential Biomarkers in Ovarian Endometriosis. Reprod. Sci. 27, 1715–1723 (2020). https://doi.org/10.1007/s43032-020-00148-z Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-020-00148-z

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endometriosis

MeSH descriptors

Biomarkers Endometriosis MicroRNAs Ovarian Diseases Biomarkers Down-Regulation Endometriosis Endometriosis Endometriosis Endometrium Endometrium Female Gene Expression Profiling Humans MicroRNAs MicroRNAs Ovarian Diseases Ovarian Diseases Ovarian Diseases Signal Transduction

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