Abstract
Endometriosis (EMS) is a common gynecological condition with apparent heterogeneity, lack of diagnostic markers, and unclear pathogenesis. A series of bioinformatics methods were employed to explore EMS’s pathological mechanisms and potential biomarkers by analyzing the combined datasets of EMS (GSE7305, GSE7307, GSE58198, E-MTAB-694), which included 34 normal, 127 eutopic, and 46 ectopic endometrium samples. Then, wet-laboratory experiments (including Western blot, qRT-PCR, and Immunohistochemistry, Immunofluorescence, CCK-8, EdU, Wound healing, Transwell, and Adhesion assays) were applied to examine the biomarkers’ expression and function in primary endometrial stromal cells. Bioinformatic analysis indicated that the core pathogenesis of EMS was dysregulated immune-inflammation and tissue remolding processes. Among the upregulated DEGs, BST2 was screened as a potential diagnostic biomarker in EMS, which associated with the revised American Fertility Society (r-AFS) stage and immune-inflammation processes of EMS. Moreover, BST2’s overexpression was affirmed in the RNA and protein levels in EMS tissues. In vitro experiments demonstrated that TNF-α promoted the expression of BST2 in ESCs. And BST2 knockdown inhibited migration, invasion, adhesion, and inflammation except for the proliferation of ESCs, probably via the TNF-α/NF-κB pathway. Through a combination of wet and dry studies, we concluded that the core pathogenesis of endometriosis was dysregulated immune-inflammation and tissue remolding, and BST2 might be a potential diagnostic and therapeutic target in endometriosis.
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Data Availability
The datasets GSE7305, GSE7307, E-MTAB-694, GSE51981, GSE105764, GSE47360, and GSE25628, used in this study can be found in the NCBI GEO database (https://www.ncbi.nlm.nih.gov/geo/).
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Acknowledgements
The authors would like to thank the GEO training course of Helix-Life as well as Biotrainee for the training of bioinformatics analysis, and Dr. Jianming Zeng (CEO of Biotrainee) and Dr. Guozi (Chongqing Medical University) for generously sharing their experience and codes.
Funding
This work was supported by the National Natural Science Foundation of China (Grant number 81671437 to X.F., Grant number 81771558 to X.X., Grant number 81801425 to T.Z.), Natural Science Foundation of Hunan Province (Grant number 2023JJ40892 to L.J.), and Natural Science Foundation of Changsha City (Grant number kq2208352 to L.J.). The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.
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L.J. and X.F. conceived and designed the study. L.J., S.W., X.W., and T.Z. acquired and analyzed data. L.J., X.X., F.Z., and J.M. helped interpret data and prepare figures and tables. L.J. drafted the manuscript. X.F. and X.X. revised the manuscript. All authors reviewed the manuscript. L.J and X.F. gave the final approval of the version to be published.
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Jiang, L., Wang, S., Xia, X. et al. Novel Diagnostic Biomarker BST2 Identified by Integrated Transcriptomics Promotes the Development of Endometriosis via the TNF-α/NF-κB Signaling Pathway. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10666-z
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DOI: https://doi.org/10.1007/s10528-024-10666-z