Identification and validation of a signature based on macrophage cell marker genes to predict recurrent miscarriage by integrated analysis of single-cell and bulk RNA-sequencing
Recurrent miscarriage (RM) is a chronic, heterogeneous autoimmune disease that has serious social and personal consequences. No valid and reliable diagnostic markers or therapeutic targets for RM have been identified. Macrophages impact the innate immune system and can be used as diagnostic and prog...
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| Published in | Frontiers in immunology Vol. 13; p. 1053819 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
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11.11.2022
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| Abstract | Recurrent miscarriage (RM) is a chronic, heterogeneous autoimmune disease that has serious social and personal consequences. No valid and reliable diagnostic markers or therapeutic targets for RM have been identified. Macrophages impact the innate immune system and can be used as diagnostic and prognostic markers for many diseases. We first collected 16 decidua and villi tissue samples from 5 normal patients and 3 RM patients for single-cell RNA sequencing data analysis and identified 1293 macrophage marker genes. We then screened a recurrent miscarriage cohort (GSE165004) for 186 macrophage-associated marker genes that were significantly differentially expressed between RM patients and the normal pregnancy endometrial tissues, and performed a functional enrichment analysis of differentially expressed genes. We then identified seven core genes (ACTR2, CD2AP, MBNL2, NCSTN, PUM1, RPN2, and TBC1D12) from the above differentially expressed gene group that are closely related to RM using the LASSO, Random Forest and SVM-RFE algorithms. We also used GSE26787 and our own collection of clinical specimens to further evaluate the diagnostic value of the target genes. A nomogram was constructed of the expression levels of these seven target genes to predict RM, and the ROC and calibration curves showed that our nomogram had a high diagnostic value for RM. These results suggest that ACTR2 and NCSTN may be potential targets for preventative RM treatments. |
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| AbstractList | Recurrent miscarriage (RM) is a chronic, heterogeneous autoimmune disease that has serious social and personal consequences. No valid and reliable diagnostic markers or therapeutic targets for RM have been identified. Macrophages impact the innate immune system and can be used as diagnostic and prognostic markers for many diseases. We first collected 16 decidua and villi tissue samples from 5 normal patients and 3 RM patients for single-cell RNA sequencing data analysis and identified 1293 macrophage marker genes. We then screened a recurrent miscarriage cohort (GSE165004) for 186 macrophage-associated marker genes that were significantly differentially expressed between RM patients and the normal pregnancy endometrial tissues, and performed a functional enrichment analysis of differentially expressed genes. We then identified seven core genes (ACTR2, CD2AP, MBNL2, NCSTN, PUM1, RPN2, and TBC1D12) from the above differentially expressed gene group that are closely related to RM using the LASSO, Random Forest and SVM-RFE algorithms. We also used GSE26787 and our own collection of clinical specimens to further evaluate the diagnostic value of the target genes. A nomogram was constructed of the expression levels of these seven target genes to predict RM, and the ROC and calibration curves showed that our nomogram had a high diagnostic value for RM. These results suggest that ACTR2 and NCSTN may be potential targets for preventative RM treatments. Recurrent miscarriage (RM) is a chronic, heterogeneous autoimmune disease that has serious social and personal consequences. No valid and reliable diagnostic markers or therapeutic targets for RM have been identified. Macrophages impact the innate immune system and can be used as diagnostic and prognostic markers for many diseases. We first collected 16 decidua and villi tissue samples from 5 normal patients and 3 RM patients for single-cell RNA sequencing data analysis and identified 1293 macrophage marker genes. We then screened a recurrent miscarriage cohort (GSE165004) for 186 macrophage-associated marker genes that were significantly differentially expressed between RM patients and the normal pregnancy endometrial tissues, and performed a functional enrichment analysis of differentially expressed genes. We then identified seven core genes (ACTR2, CD2AP, MBNL2, NCSTN, PUM1, RPN2, and TBC1D12) from the above differentially expressed gene group that are closely related to RM using the LASSO, Random Forest and SVM-RFE algorithms. We also used GSE26787 and our own collection of clinical specimens to further evaluate the diagnostic value of the target genes. A nomogram was constructed of the expression levels of these seven target genes to predict RM, and the ROC and calibration curves showed that our nomogram had a high diagnostic value for RM. These results suggest that ACTR2 and NCSTN may be potential targets for preventative RM treatments.Recurrent miscarriage (RM) is a chronic, heterogeneous autoimmune disease that has serious social and personal consequences. No valid and reliable diagnostic markers or therapeutic targets for RM have been identified. Macrophages impact the innate immune system and can be used as diagnostic and prognostic markers for many diseases. We first collected 16 decidua and villi tissue samples from 5 normal patients and 3 RM patients for single-cell RNA sequencing data analysis and identified 1293 macrophage marker genes. We then screened a recurrent miscarriage cohort (GSE165004) for 186 macrophage-associated marker genes that were significantly differentially expressed between RM patients and the normal pregnancy endometrial tissues, and performed a functional enrichment analysis of differentially expressed genes. We then identified seven core genes (ACTR2, CD2AP, MBNL2, NCSTN, PUM1, RPN2, and TBC1D12) from the above differentially expressed gene group that are closely related to RM using the LASSO, Random Forest and SVM-RFE algorithms. We also used GSE26787 and our own collection of clinical specimens to further evaluate the diagnostic value of the target genes. A nomogram was constructed of the expression levels of these seven target genes to predict RM, and the ROC and calibration curves showed that our nomogram had a high diagnostic value for RM. These results suggest that ACTR2 and NCSTN may be potential targets for preventative RM treatments. |
| Author | Huang, Weiyu Liu, Bo Chen, Saiqiong Fu, Xiaoqian Yang, Yihua Bi, Yin Li, Ting Dong, Mingyou Wei, Peiru |
| AuthorAffiliation | 4 The Key Laboratory of Molecular Pathology (For Hepatobiliary Diseases) of Guangxi, Affiliated Hospital of Youjiang Medical University for Nationalities , Baise , China 5 Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China 3 The Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education , Nanning , China 2 Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Guangxi Medical University , Nanning , China 1 Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University , Nanning , China |
| AuthorAffiliation_xml | – name: 2 Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Guangxi Medical University , Nanning , China – name: 4 The Key Laboratory of Molecular Pathology (For Hepatobiliary Diseases) of Guangxi, Affiliated Hospital of Youjiang Medical University for Nationalities , Baise , China – name: 1 Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University , Nanning , China – name: 5 Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China – name: 3 The Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education , Nanning , China |
| Author_xml | – sequence: 1 givenname: Peiru surname: Wei fullname: Wei, Peiru – sequence: 2 givenname: Mingyou surname: Dong fullname: Dong, Mingyou – sequence: 3 givenname: Yin surname: Bi fullname: Bi, Yin – sequence: 4 givenname: Saiqiong surname: Chen fullname: Chen, Saiqiong – sequence: 5 givenname: Weiyu surname: Huang fullname: Huang, Weiyu – sequence: 6 givenname: Ting surname: Li fullname: Li, Ting – sequence: 7 givenname: Bo surname: Liu fullname: Liu, Bo – sequence: 8 givenname: Xiaoqian surname: Fu fullname: Fu, Xiaoqian – sequence: 9 givenname: Yihua surname: Yang fullname: Yang, Yihua |
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| Copyright | Copyright © 2022 Wei, Dong, Bi, Chen, Huang, Li, Liu, Fu and Yang. Copyright © 2022 Wei, Dong, Bi, Chen, Huang, Li, Liu, Fu and Yang 2022 Wei, Dong, Bi, Chen, Huang, Li, Liu, Fu and Yang |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Yin Tailang, Reproductive Medicine Center, Wuhan University, China This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology Reviewed by: Rong Li, Peking University Third Hospital, China; Xi Xia, Shenzhen Hospital, Peking University, China; Ye Cao, The Chinese University of Hong Kong, Hong Kong, SAR China |
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| Title | Identification and validation of a signature based on macrophage cell marker genes to predict recurrent miscarriage by integrated analysis of single-cell and bulk RNA-sequencing |
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