Cargando…
Construction and validation of a transcription factors-based prognostic signature for ovarian cancer
BACKGROUND: Ovarian cancer (OC) is one of the most common and lethal malignant tumors worldwide and the prognosis of OC remains unsatisfactory. Transcription factors (TFs) are demonstrated to be associated with the clinical outcome of many types of cancers, yet their roles in the prognostic predicti...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886838/ https://www.ncbi.nlm.nih.gov/pubmed/35227285 http://dx.doi.org/10.1186/s13048-021-00938-2 |
_version_ | 1784660766124670976 |
---|---|
author | Cheng, Qingyuan Li, Liman Yu, Mingxia |
author_facet | Cheng, Qingyuan Li, Liman Yu, Mingxia |
author_sort | Cheng, Qingyuan |
collection | PubMed |
description | BACKGROUND: Ovarian cancer (OC) is one of the most common and lethal malignant tumors worldwide and the prognosis of OC remains unsatisfactory. Transcription factors (TFs) are demonstrated to be associated with the clinical outcome of many types of cancers, yet their roles in the prognostic prediction and gene regulatory network in patients with OC need to be further investigated. METHODS: TFs from GEO datasets were collected and analyzed. Differential expression analysis, WGCNA and Cox-LASSO regression model were used to identify the hub-TFs and a prognostic signature based on these TFs was constructed and validated. Moreover, tumor-infiltrating immune cells were analyzed, and a nomogram containing age, histology, FIGO_stage and TFs-based signature were established. Potential biological functions, pathways and the gene regulatory network of TFs in signature was also explored. RESULTS: In this study, 6 TFs significantly associated with the prognosis of OC were identified. These TFs were used to build up a TFs-based signature for predicting the survival of patients with OC. Patients with OC in training and testing datasets were divided into high-risk and low-risk groups, according to the median value of risk scores determined by the signature. The two groups were further used to validate the performance of the signature, and the results showed the TFs-based signature had effective prediction ability. Immune infiltrating analysis was conducted and abundance of B cells naïve, T cells CD4 memory resting, Macrophages M2 and Mast cells activated were significantly higher in high-risk group. A nomogram based on the signature was established and illustrated good predictive efficiencies for 1, 2, and 3-year overall survival. Furthermore, the construction of the TFs-target gene regulatory network revealed the potential mechanisms of TFs in OC. CONCLUSIONS: To our best knowledge, it is for the first time to develop a prognostic signature based on TFs in OC. The TFs-based signature is proven to be effective in predicting the survival of patients with OC. Our study may facilitate the clinical decision-making for patients with OC and help to elucidate the underlying mechanism of TFs in OC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-021-00938-2. |
format | Online Article Text |
id | pubmed-8886838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-88868382022-03-17 Construction and validation of a transcription factors-based prognostic signature for ovarian cancer Cheng, Qingyuan Li, Liman Yu, Mingxia J Ovarian Res Research BACKGROUND: Ovarian cancer (OC) is one of the most common and lethal malignant tumors worldwide and the prognosis of OC remains unsatisfactory. Transcription factors (TFs) are demonstrated to be associated with the clinical outcome of many types of cancers, yet their roles in the prognostic prediction and gene regulatory network in patients with OC need to be further investigated. METHODS: TFs from GEO datasets were collected and analyzed. Differential expression analysis, WGCNA and Cox-LASSO regression model were used to identify the hub-TFs and a prognostic signature based on these TFs was constructed and validated. Moreover, tumor-infiltrating immune cells were analyzed, and a nomogram containing age, histology, FIGO_stage and TFs-based signature were established. Potential biological functions, pathways and the gene regulatory network of TFs in signature was also explored. RESULTS: In this study, 6 TFs significantly associated with the prognosis of OC were identified. These TFs were used to build up a TFs-based signature for predicting the survival of patients with OC. Patients with OC in training and testing datasets were divided into high-risk and low-risk groups, according to the median value of risk scores determined by the signature. The two groups were further used to validate the performance of the signature, and the results showed the TFs-based signature had effective prediction ability. Immune infiltrating analysis was conducted and abundance of B cells naïve, T cells CD4 memory resting, Macrophages M2 and Mast cells activated were significantly higher in high-risk group. A nomogram based on the signature was established and illustrated good predictive efficiencies for 1, 2, and 3-year overall survival. Furthermore, the construction of the TFs-target gene regulatory network revealed the potential mechanisms of TFs in OC. CONCLUSIONS: To our best knowledge, it is for the first time to develop a prognostic signature based on TFs in OC. The TFs-based signature is proven to be effective in predicting the survival of patients with OC. Our study may facilitate the clinical decision-making for patients with OC and help to elucidate the underlying mechanism of TFs in OC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-021-00938-2. BioMed Central 2022-02-28 /pmc/articles/PMC8886838/ /pubmed/35227285 http://dx.doi.org/10.1186/s13048-021-00938-2 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 | Research Cheng, Qingyuan Li, Liman Yu, Mingxia Construction and validation of a transcription factors-based prognostic signature for ovarian cancer |
title | Construction and validation of a transcription factors-based prognostic signature for ovarian cancer |
title_full | Construction and validation of a transcription factors-based prognostic signature for ovarian cancer |
title_fullStr | Construction and validation of a transcription factors-based prognostic signature for ovarian cancer |
title_full_unstemmed | Construction and validation of a transcription factors-based prognostic signature for ovarian cancer |
title_short | Construction and validation of a transcription factors-based prognostic signature for ovarian cancer |
title_sort | construction and validation of a transcription factors-based prognostic signature for ovarian cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886838/ https://www.ncbi.nlm.nih.gov/pubmed/35227285 http://dx.doi.org/10.1186/s13048-021-00938-2 |
work_keys_str_mv | AT chengqingyuan constructionandvalidationofatranscriptionfactorsbasedprognosticsignatureforovariancancer AT liliman constructionandvalidationofatranscriptionfactorsbasedprognosticsignatureforovariancancer AT yumingxia constructionandvalidationofatranscriptionfactorsbasedprognosticsignatureforovariancancer |