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Establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer
BACKGROUND: Ovarian cancer (OC) is an invasive gynaecologic cancer with a high cancer-related death rate. The purpose of this study was to establish an invasion-related multigene signature to predict the prognostic risk of OC. METHODS: We extracted 97 invasion-related genes from The Cancer Genome At...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922755/ https://www.ncbi.nlm.nih.gov/pubmed/35292033 http://dx.doi.org/10.1186/s12935-022-02502-4 |
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author | Liang, Leilei Li, Jian Yu, Jing Liu, Jing Xiu, Lin Zeng, Jia Wang, Tiantian Li, Ning Wu, Lingying |
author_facet | Liang, Leilei Li, Jian Yu, Jing Liu, Jing Xiu, Lin Zeng, Jia Wang, Tiantian Li, Ning Wu, Lingying |
author_sort | Liang, Leilei |
collection | PubMed |
description | BACKGROUND: Ovarian cancer (OC) is an invasive gynaecologic cancer with a high cancer-related death rate. The purpose of this study was to establish an invasion-related multigene signature to predict the prognostic risk of OC. METHODS: We extracted 97 invasion-related genes from The Cancer Genome Atlas (TCGA) database. Then, the ConsensusClusterPlus and limma packages were used to calculate differentially expressed genes (DEGs). To calculate the immune scores of the molecular subtypes, we used ESTIMATE to evaluate the stromal score, immune score and ESTIMATE score. MCP-counter and the GSVA package ssgsea were used to evaluate the types of infiltrating immune cells. Survival and nomogram analyses were performed to explore the prognostic value of the signature. Finally, qPCR, immunohistochemistry staining and functional assays were used to evaluate the expression and biological abilities of the signature genes in OC. RESULTS: Based on the consistent clustering of invasion-related genes, cases in the OC datasets were divided into two subtypes. A significant difference was observed in prognosis between the two subtypes. Most genes were highly expressed in the C1 group. Based on the C1 group genes, we constructed an invasion-related 6-gene prognostic risk model. Furthermore, to verify the signature, we used the TCGA-test and GSE32062 and GSE17260 chip datasets for testing and finally obtained a good risk prediction effect in those datasets. Moreover, the results of the qPCR and immunohistochemistry staining assays revealed that KIF26B, VSIG4 and COL6A6 were upregulated and that FOXJ1, MXRA5 and CXCL9 were downregulated in OC tissues. The functional study showed that the expression of KIF26B, VSIG4, COL6A6, FOXJ1, MXRA5 and CXCL9 can regulate the migration and invasion abilities of OC cells. CONCLUSION: We developed a 6-gene prognostic stratification system (FOXJ1, MXRA5, KIF26B, VSIG4, CXCL9 and COL6A6) that is independent of clinical features. These results suggest that the signature could potentially be used to evaluate the prognostic risk of OC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02502-4. |
format | Online Article Text |
id | pubmed-8922755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-89227552022-03-22 Establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer Liang, Leilei Li, Jian Yu, Jing Liu, Jing Xiu, Lin Zeng, Jia Wang, Tiantian Li, Ning Wu, Lingying Cancer Cell Int Primary Research BACKGROUND: Ovarian cancer (OC) is an invasive gynaecologic cancer with a high cancer-related death rate. The purpose of this study was to establish an invasion-related multigene signature to predict the prognostic risk of OC. METHODS: We extracted 97 invasion-related genes from The Cancer Genome Atlas (TCGA) database. Then, the ConsensusClusterPlus and limma packages were used to calculate differentially expressed genes (DEGs). To calculate the immune scores of the molecular subtypes, we used ESTIMATE to evaluate the stromal score, immune score and ESTIMATE score. MCP-counter and the GSVA package ssgsea were used to evaluate the types of infiltrating immune cells. Survival and nomogram analyses were performed to explore the prognostic value of the signature. Finally, qPCR, immunohistochemistry staining and functional assays were used to evaluate the expression and biological abilities of the signature genes in OC. RESULTS: Based on the consistent clustering of invasion-related genes, cases in the OC datasets were divided into two subtypes. A significant difference was observed in prognosis between the two subtypes. Most genes were highly expressed in the C1 group. Based on the C1 group genes, we constructed an invasion-related 6-gene prognostic risk model. Furthermore, to verify the signature, we used the TCGA-test and GSE32062 and GSE17260 chip datasets for testing and finally obtained a good risk prediction effect in those datasets. Moreover, the results of the qPCR and immunohistochemistry staining assays revealed that KIF26B, VSIG4 and COL6A6 were upregulated and that FOXJ1, MXRA5 and CXCL9 were downregulated in OC tissues. The functional study showed that the expression of KIF26B, VSIG4, COL6A6, FOXJ1, MXRA5 and CXCL9 can regulate the migration and invasion abilities of OC cells. CONCLUSION: We developed a 6-gene prognostic stratification system (FOXJ1, MXRA5, KIF26B, VSIG4, CXCL9 and COL6A6) that is independent of clinical features. These results suggest that the signature could potentially be used to evaluate the prognostic risk of OC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02502-4. BioMed Central 2022-03-15 /pmc/articles/PMC8922755/ /pubmed/35292033 http://dx.doi.org/10.1186/s12935-022-02502-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Liang, Leilei Li, Jian Yu, Jing Liu, Jing Xiu, Lin Zeng, Jia Wang, Tiantian Li, Ning Wu, Lingying Establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer |
title | Establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer |
title_full | Establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer |
title_fullStr | Establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer |
title_full_unstemmed | Establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer |
title_short | Establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer |
title_sort | establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922755/ https://www.ncbi.nlm.nih.gov/pubmed/35292033 http://dx.doi.org/10.1186/s12935-022-02502-4 |
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