Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13

Abstract Background Metastasis, the leading cause of cancer-related death in patients diagnosed with ovarian cancer (OC), is a complex process that involves multiple biological effects. With the continuous development of sequencing technology, single-cell sequence has emerged as a promising strategy...

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Main Authors: Jiahao Guo, Xiaoyang Han, Jie Li, Zhefeng Li, Junjie Yi, Yan Gao, Xiaoting Zhao, Wentao Yue
Format: Article
Language:English
Published: BMC 2023-04-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-023-04094-7
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author Jiahao Guo
Xiaoyang Han
Jie Li
Zhefeng Li
Junjie Yi
Yan Gao
Xiaoting Zhao
Wentao Yue
author_facet Jiahao Guo
Xiaoyang Han
Jie Li
Zhefeng Li
Junjie Yi
Yan Gao
Xiaoting Zhao
Wentao Yue
author_sort Jiahao Guo
collection DOAJ
description Abstract Background Metastasis, the leading cause of cancer-related death in patients diagnosed with ovarian cancer (OC), is a complex process that involves multiple biological effects. With the continuous development of sequencing technology, single-cell sequence has emerged as a promising strategy to understand the pathogenesis of ovarian cancer. Methods Through integrating 10 × single-cell data from 12 samples, we developed a single-cell map of primary and metastatic OC. By copy-number variations analysis, pseudotime analysis, enrichment analysis, and cell–cell communication analysis, we explored the heterogeneity among OC cells. We performed differential expression analysis and high dimensional weighted gene co-expression network analysis to identify the hub genes of C4. The effects of RAB13 on OC cell lines were validated in vitro. Results We discovered a cell subcluster, referred to as C4, that is closely associated with metastasis and poor prognosis in OC. This subcluster correlated with an epithelial–mesenchymal transition (EMT) and angiogenesis signature and RAB13 was identified as the key marker of it. Downregulation of RAB13 resulted in a reduction of OC cells migration and invasion. Additionally, we predicted several potential drugs that might inhibit RAB13. Conclusions Our study has identified a cell subcluster that is closely linked to metastasis in OC, and we have also identified RAB13 as its hub gene that has great potential to become a new therapeutic target for OC.
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spelling doaj.art-5957ccdaab4943398b08c1e675442e3e2023-04-16T11:23:46ZengBMCJournal of Translational Medicine1479-58762023-04-0121111510.1186/s12967-023-04094-7Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13Jiahao Guo0Xiaoyang Han1Jie Li2Zhefeng Li3Junjie Yi4Yan Gao5Xiaoting Zhao6Wentao Yue7Central Laboratory, Beijing Maternal and Child Health Care Hospital, Beijing Obstetrics and Gynecology Hospital, Capital Medical UniversityCentral Laboratory, Beijing Maternal and Child Health Care Hospital, Beijing Obstetrics and Gynecology Hospital, Capital Medical UniversityCentral Laboratory, Beijing Maternal and Child Health Care Hospital, Beijing Obstetrics and Gynecology Hospital, Capital Medical UniversityCentral Laboratory, Beijing Maternal and Child Health Care Hospital, Beijing Obstetrics and Gynecology Hospital, Capital Medical UniversityCentral Laboratory, Beijing Maternal and Child Health Care Hospital, Beijing Obstetrics and Gynecology Hospital, Capital Medical UniversityCentral Laboratory, Beijing Maternal and Child Health Care Hospital, Beijing Obstetrics and Gynecology Hospital, Capital Medical UniversityCentral Laboratory, Beijing Maternal and Child Health Care Hospital, Beijing Obstetrics and Gynecology Hospital, Capital Medical UniversityCentral Laboratory, Beijing Maternal and Child Health Care Hospital, Beijing Obstetrics and Gynecology Hospital, Capital Medical UniversityAbstract Background Metastasis, the leading cause of cancer-related death in patients diagnosed with ovarian cancer (OC), is a complex process that involves multiple biological effects. With the continuous development of sequencing technology, single-cell sequence has emerged as a promising strategy to understand the pathogenesis of ovarian cancer. Methods Through integrating 10 × single-cell data from 12 samples, we developed a single-cell map of primary and metastatic OC. By copy-number variations analysis, pseudotime analysis, enrichment analysis, and cell–cell communication analysis, we explored the heterogeneity among OC cells. We performed differential expression analysis and high dimensional weighted gene co-expression network analysis to identify the hub genes of C4. The effects of RAB13 on OC cell lines were validated in vitro. Results We discovered a cell subcluster, referred to as C4, that is closely associated with metastasis and poor prognosis in OC. This subcluster correlated with an epithelial–mesenchymal transition (EMT) and angiogenesis signature and RAB13 was identified as the key marker of it. Downregulation of RAB13 resulted in a reduction of OC cells migration and invasion. Additionally, we predicted several potential drugs that might inhibit RAB13. Conclusions Our study has identified a cell subcluster that is closely linked to metastasis in OC, and we have also identified RAB13 as its hub gene that has great potential to become a new therapeutic target for OC.https://doi.org/10.1186/s12967-023-04094-7Ovarian cancerMetastasisSingle-cell transcriptomicsRAB13Heterogeneity
spellingShingle Jiahao Guo
Xiaoyang Han
Jie Li
Zhefeng Li
Junjie Yi
Yan Gao
Xiaoting Zhao
Wentao Yue
Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13
Journal of Translational Medicine
Ovarian cancer
Metastasis
Single-cell transcriptomics
RAB13
Heterogeneity
title Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13
title_full Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13
title_fullStr Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13
title_full_unstemmed Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13
title_short Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13
title_sort single cell transcriptomics in ovarian cancer identify a metastasis associated cell cluster overexpressed rab13
topic Ovarian cancer
Metastasis
Single-cell transcriptomics
RAB13
Heterogeneity
url https://doi.org/10.1186/s12967-023-04094-7
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