Integrative analyses of potential biomarkers and pathways for non-obstructive azoospermia
Background: Non-obstructive azoospermia (NOA) is the most severe form of male infertility. Currently, the molecular mechanisms underlying NOA pathology have not yet been elucidated. Hence, elucidation of the mechanisms of NOA and exploration of potential biomarkers are essential for accurate diagnos...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.988047/full |
| _version_ | 1811179968851345408 |
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| author | Yucheng Zhong Xiaoqing Chen Jun Zhao Hao Deng Xiaohang Li Zhongju Xie Bingyu Zhou Zhuojie Xian Xiaoqin Li Guoqun Luo Huan Li |
| author_facet | Yucheng Zhong Xiaoqing Chen Jun Zhao Hao Deng Xiaohang Li Zhongju Xie Bingyu Zhou Zhuojie Xian Xiaoqin Li Guoqun Luo Huan Li |
| author_sort | Yucheng Zhong |
| collection | DOAJ |
| description | Background: Non-obstructive azoospermia (NOA) is the most severe form of male infertility. Currently, the molecular mechanisms underlying NOA pathology have not yet been elucidated. Hence, elucidation of the mechanisms of NOA and exploration of potential biomarkers are essential for accurate diagnosis and treatment of this disease. In the present study, we aimed to screen for biomarkers and pathways involved in NOA and reveal their potential molecular mechanisms using integrated bioinformatics.Methods: We downloaded two gene expression datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in NOA and matched the control group tissues were identified using the limma package in R software. Subsequently, Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), protein-protein interaction (PPI) network, gene-microRNAs network, and transcription factor (TF)-hub genes regulatory network analyses were performed to identify hub genes and associated pathways. Finally, we conducted immune infiltration analysis using CIBERSORT to evaluate the relationship between the hub genes and the NOA immune infiltration levels.Results: We identified 698 common DEGs, including 87 commonly upregulated and 611 commonly downregulated genes in the two datasets. GO analysis indicated that the most significantly enriched gene was protein polyglycylation, and KEGG pathway analysis revealed that the DEGs were most significantly enriched in taste transduction and pancreatic secretion signaling pathways. GSEA showed that DEGs affected the biological functions of the ribosome, focaladhesion, and protein_expor. We further identified the top 31 hub genes from the PPI network, and friends analysis of hub genes in the PPI network showed that NR4A2 had the highest score. In addition, immune infiltration analysis found that CD8+ T cells and plasma cells were significantly correlated with ODF3 expression, whereas naive B cells, plasma cells, monocytes, M2 macrophages, and resting mast cells showed significant variation in the NR4A2 gene expression group, and there were differences in T cell regulatory immune cell infiltration in the FOS gene expression groups.Conclusion: The present study successfully constructed a regulatory network of DEGs between NOA and normal controls and screened three hub genes using integrative bioinformatics analysis. In addition, our results suggest that functional changes in several immune cells in the immune microenvironment may play an important role in spermatogenesis. Our results provide a novel understanding of the molecular mechanisms of NOA and offer potential biomarkers for its diagnosis and treatment. |
| first_indexed | 2024-04-11T06:42:21Z |
| format | Article |
| id | doaj.art-47eb4161ca49485a96de8696b2bbc4e0 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T06:42:21Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-47eb4161ca49485a96de8696b2bbc4e02022-12-22T04:39:28ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-11-011310.3389/fgene.2022.988047988047Integrative analyses of potential biomarkers and pathways for non-obstructive azoospermiaYucheng Zhong0Xiaoqing Chen1Jun Zhao2Hao Deng3Xiaohang Li4Zhongju Xie5Bingyu Zhou6Zhuojie Xian7Xiaoqin Li8Guoqun Luo9Huan Li10Assisted Reproductive Technology Center, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, ChinaDepartment of Breast Surgical Oncology, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, ChinaAssisted Reproductive Technology Center, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, ChinaAssisted Reproductive Technology Center, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, ChinaAssisted Reproductive Technology Center, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, ChinaAssisted Reproductive Technology Center, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, ChinaAssisted Reproductive Technology Center, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, ChinaAssisted Reproductive Technology Center, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, ChinaAssisted Reproductive Technology Center, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, ChinaAssisted Reproductive Technology Center, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, ChinaAssisted Reproductive Technology Center, Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, Foshan, ChinaBackground: Non-obstructive azoospermia (NOA) is the most severe form of male infertility. Currently, the molecular mechanisms underlying NOA pathology have not yet been elucidated. Hence, elucidation of the mechanisms of NOA and exploration of potential biomarkers are essential for accurate diagnosis and treatment of this disease. In the present study, we aimed to screen for biomarkers and pathways involved in NOA and reveal their potential molecular mechanisms using integrated bioinformatics.Methods: We downloaded two gene expression datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in NOA and matched the control group tissues were identified using the limma package in R software. Subsequently, Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), protein-protein interaction (PPI) network, gene-microRNAs network, and transcription factor (TF)-hub genes regulatory network analyses were performed to identify hub genes and associated pathways. Finally, we conducted immune infiltration analysis using CIBERSORT to evaluate the relationship between the hub genes and the NOA immune infiltration levels.Results: We identified 698 common DEGs, including 87 commonly upregulated and 611 commonly downregulated genes in the two datasets. GO analysis indicated that the most significantly enriched gene was protein polyglycylation, and KEGG pathway analysis revealed that the DEGs were most significantly enriched in taste transduction and pancreatic secretion signaling pathways. GSEA showed that DEGs affected the biological functions of the ribosome, focaladhesion, and protein_expor. We further identified the top 31 hub genes from the PPI network, and friends analysis of hub genes in the PPI network showed that NR4A2 had the highest score. In addition, immune infiltration analysis found that CD8+ T cells and plasma cells were significantly correlated with ODF3 expression, whereas naive B cells, plasma cells, monocytes, M2 macrophages, and resting mast cells showed significant variation in the NR4A2 gene expression group, and there were differences in T cell regulatory immune cell infiltration in the FOS gene expression groups.Conclusion: The present study successfully constructed a regulatory network of DEGs between NOA and normal controls and screened three hub genes using integrative bioinformatics analysis. In addition, our results suggest that functional changes in several immune cells in the immune microenvironment may play an important role in spermatogenesis. Our results provide a novel understanding of the molecular mechanisms of NOA and offer potential biomarkers for its diagnosis and treatment.https://www.frontiersin.org/articles/10.3389/fgene.2022.988047/fullnon-obstructive azoospermiadifferentially expressed geneshub genesbioinformaticsbiomarker |
| spellingShingle | Yucheng Zhong Xiaoqing Chen Jun Zhao Hao Deng Xiaohang Li Zhongju Xie Bingyu Zhou Zhuojie Xian Xiaoqin Li Guoqun Luo Huan Li Integrative analyses of potential biomarkers and pathways for non-obstructive azoospermia Frontiers in Genetics non-obstructive azoospermia differentially expressed genes hub genes bioinformatics biomarker |
| title | Integrative analyses of potential biomarkers and pathways for non-obstructive azoospermia |
| title_full | Integrative analyses of potential biomarkers and pathways for non-obstructive azoospermia |
| title_fullStr | Integrative analyses of potential biomarkers and pathways for non-obstructive azoospermia |
| title_full_unstemmed | Integrative analyses of potential biomarkers and pathways for non-obstructive azoospermia |
| title_short | Integrative analyses of potential biomarkers and pathways for non-obstructive azoospermia |
| title_sort | integrative analyses of potential biomarkers and pathways for non obstructive azoospermia |
| topic | non-obstructive azoospermia differentially expressed genes hub genes bioinformatics biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.988047/full |
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