Elevated expression of glycolytic genes as a prominent feature of early-onset preeclampsia: insights from integrative transcriptomic analysis
Introduction: Preeclampsia (PE), a notable pregnancy-related disorder, leads to 40,000+ maternal deaths yearly. Recent research shows PE divides into early-onset (EOPE) and late-onset (LOPE) subtypes, each with distinct clinical features and outcomes. However, the molecular characteristics of variou...
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1248771/full |
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| author | Jie He Jie He Jie He Huan Yang Zheng Liu Zheng Liu Zheng Liu Miaomiao Chen Ying Ye Yuelan Tao Yuelan Tao Yuelan Tao Shuhong Li Jie Fang Jie Fang Jie Fang Jiacheng Xu Jiacheng Xu Jiacheng Xu Xiafei Wu Xiafei Wu Xiafei Wu Hongbo Qi Hongbo Qi Hongbo Qi Hongbo Qi |
| author_facet | Jie He Jie He Jie He Huan Yang Zheng Liu Zheng Liu Zheng Liu Miaomiao Chen Ying Ye Yuelan Tao Yuelan Tao Yuelan Tao Shuhong Li Jie Fang Jie Fang Jie Fang Jiacheng Xu Jiacheng Xu Jiacheng Xu Xiafei Wu Xiafei Wu Xiafei Wu Hongbo Qi Hongbo Qi Hongbo Qi Hongbo Qi |
| author_sort | Jie He |
| collection | DOAJ |
| description | Introduction: Preeclampsia (PE), a notable pregnancy-related disorder, leads to 40,000+ maternal deaths yearly. Recent research shows PE divides into early-onset (EOPE) and late-onset (LOPE) subtypes, each with distinct clinical features and outcomes. However, the molecular characteristics of various subtypes are currently subject to debate and are not consistent.Methods: We integrated transcriptomic expression data from a total of 372 placental samples across 8 publicly available databases via combat algorithm. Then, a variety of strategies including Random Forest Recursive Feature Elimination (RF-RFE), differential analysis, oposSOM, and Weighted Correlation Network Analysis were employed to identify the characteristic genes of the EOPE and LOPE subtypes. Finally, we conducted in vitro experiments on the key gene HK2 in HTR8/SVneo cells to explore its function.Results: Our results revealed a complex classification of PE placental samples, wherein EOPE manifests as a highly homogeneous sample group characterized by hypoxia and HIF1A activation. Among the core features is the upregulation of glycolysis-related genes, particularly HK2, in the placenta-an observation corroborated by independent validation data and single-cell data. Building on the pronounced correlation between HK2 and EOPE, we conducted in vitro experiments to assess the potential functional impact of HK2 on trophoblast cells. Additionally, the LOPE samples exhibit strong heterogeneity and lack distinct features, suggesting a complex molecular makeup for this subtype. Unsupervised clustering analysis indicates that LOPE likely comprises at least two distinct subtypes, linked to cell-environment interaction and cytokine and protein modification functionalities.Discussion: In summary, these findings elucidate potential mechanistic differences between the two PE subtypes, lend support to the hypothesis of classifying PE based on gestational weeks, and emphasize the potential significant role of glycolysis-related genes, especially HK2 in EOPE. |
| first_indexed | 2024-03-11T21:53:19Z |
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| institution | Directory Open Access Journal |
| issn | 2296-889X |
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| last_indexed | 2024-03-11T21:53:19Z |
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| spelling | doaj.art-10a44a56edf843b3a70dfcffde21059f2023-09-26T06:41:59ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-09-011010.3389/fmolb.2023.12487711248771Elevated expression of glycolytic genes as a prominent feature of early-onset preeclampsia: insights from integrative transcriptomic analysisJie He0Jie He1Jie He2Huan Yang3Zheng Liu4Zheng Liu5Zheng Liu6Miaomiao Chen7Ying Ye8Yuelan Tao9Yuelan Tao10Yuelan Tao11Shuhong Li12Jie Fang13Jie Fang14Jie Fang15Jiacheng Xu16Jiacheng Xu17Jiacheng Xu18Xiafei Wu19Xiafei Wu20Xiafei Wu21Hongbo Qi22Hongbo Qi23Hongbo Qi24Hongbo Qi25Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, ChinaJoint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaDepartment of Obstetrics, Chongqing University Three Gorges Hospital, Chongqing, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, ChinaJoint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaMaternal and Child Health Hospital of Hubei Province, Wuhan, ChinaDepartment of Cardiothoracic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, ChinaJoint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaDepartment of Oncology, Chengdu Second People’s Hospital, Chengdu, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, ChinaJoint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, ChinaJoint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, ChinaJoint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaDepartment of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, ChinaJoint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, ChinaDepartment of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, Chongqing, ChinaIntroduction: Preeclampsia (PE), a notable pregnancy-related disorder, leads to 40,000+ maternal deaths yearly. Recent research shows PE divides into early-onset (EOPE) and late-onset (LOPE) subtypes, each with distinct clinical features and outcomes. However, the molecular characteristics of various subtypes are currently subject to debate and are not consistent.Methods: We integrated transcriptomic expression data from a total of 372 placental samples across 8 publicly available databases via combat algorithm. Then, a variety of strategies including Random Forest Recursive Feature Elimination (RF-RFE), differential analysis, oposSOM, and Weighted Correlation Network Analysis were employed to identify the characteristic genes of the EOPE and LOPE subtypes. Finally, we conducted in vitro experiments on the key gene HK2 in HTR8/SVneo cells to explore its function.Results: Our results revealed a complex classification of PE placental samples, wherein EOPE manifests as a highly homogeneous sample group characterized by hypoxia and HIF1A activation. Among the core features is the upregulation of glycolysis-related genes, particularly HK2, in the placenta-an observation corroborated by independent validation data and single-cell data. Building on the pronounced correlation between HK2 and EOPE, we conducted in vitro experiments to assess the potential functional impact of HK2 on trophoblast cells. Additionally, the LOPE samples exhibit strong heterogeneity and lack distinct features, suggesting a complex molecular makeup for this subtype. Unsupervised clustering analysis indicates that LOPE likely comprises at least two distinct subtypes, linked to cell-environment interaction and cytokine and protein modification functionalities.Discussion: In summary, these findings elucidate potential mechanistic differences between the two PE subtypes, lend support to the hypothesis of classifying PE based on gestational weeks, and emphasize the potential significant role of glycolysis-related genes, especially HK2 in EOPE.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1248771/fullpreeclampsiaplacentagestational hypertensiontranscriptomicsmicroarraysingle-cell sequencing |
| spellingShingle | Jie He Jie He Jie He Huan Yang Zheng Liu Zheng Liu Zheng Liu Miaomiao Chen Ying Ye Yuelan Tao Yuelan Tao Yuelan Tao Shuhong Li Jie Fang Jie Fang Jie Fang Jiacheng Xu Jiacheng Xu Jiacheng Xu Xiafei Wu Xiafei Wu Xiafei Wu Hongbo Qi Hongbo Qi Hongbo Qi Hongbo Qi Elevated expression of glycolytic genes as a prominent feature of early-onset preeclampsia: insights from integrative transcriptomic analysis Frontiers in Molecular Biosciences preeclampsia placenta gestational hypertension transcriptomics microarray single-cell sequencing |
| title | Elevated expression of glycolytic genes as a prominent feature of early-onset preeclampsia: insights from integrative transcriptomic analysis |
| title_full | Elevated expression of glycolytic genes as a prominent feature of early-onset preeclampsia: insights from integrative transcriptomic analysis |
| title_fullStr | Elevated expression of glycolytic genes as a prominent feature of early-onset preeclampsia: insights from integrative transcriptomic analysis |
| title_full_unstemmed | Elevated expression of glycolytic genes as a prominent feature of early-onset preeclampsia: insights from integrative transcriptomic analysis |
| title_short | Elevated expression of glycolytic genes as a prominent feature of early-onset preeclampsia: insights from integrative transcriptomic analysis |
| title_sort | elevated expression of glycolytic genes as a prominent feature of early onset preeclampsia insights from integrative transcriptomic analysis |
| topic | preeclampsia placenta gestational hypertension transcriptomics microarray single-cell sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1248771/full |
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