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A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients

BACKGROUND: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and its prevalence is increasing. As an emerging therapy with a promising efficacy, immunotherapy has been extensively applied in the treatment of solid tumors. In addition, chromatin regulators (CRs...

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Autores principales: Liu, Zesi, Yang, Hongxia, Chen, Ziyu, Jing, Chunli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578220/
https://www.ncbi.nlm.nih.gov/pubmed/36253800
http://dx.doi.org/10.1186/s41065-022-00253-w
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author Liu, Zesi
Yang, Hongxia
Chen, Ziyu
Jing, Chunli
author_facet Liu, Zesi
Yang, Hongxia
Chen, Ziyu
Jing, Chunli
author_sort Liu, Zesi
collection PubMed
description BACKGROUND: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and its prevalence is increasing. As an emerging therapy with a promising efficacy, immunotherapy has been extensively applied in the treatment of solid tumors. In addition, chromatin regulators (CRs), as essential upstream regulators of epigenetics, play a significant role in tumorigenesis and cancer development. METHODS: CRs and immune checkpoint-related genes (ICRGs) were obtained from the previous top research. The Genome Cancer Atlas (TCGA) was utilized to acquire the mRNA expression and clinical information of patients with EC. Correlation analysis was utilized for screen CRs-related ICRGs (CRRICRGs). By Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, prognosis related CRRICRGs were screened out and risk model was constructed. The Kaplan–Meier curve was used to estimate the prognosis between high- and low-risk group. By comparing the IC50 value, the drugs sensitivity difference was explored. We obtained small molecule drugs for the treatment of UCEC patients based on CAMP dataset. RESULTS: We successfully constructed a 9 CRRICRs-based prognostic signature for patients with UCEC and found the riskscore was an independent prognostic factor. The results of functional analysis suggested that CRRICRGs may be involved in immune processes associated with cancer. Immune characteristics analysis provided further evidence that the CRRICRGs-based model was correlated with immune cells infiltration and immune checkpoint. Eight small molecule drugs that may be effective for the treatment of UCEC patients were screened. Effective drugs identified by drug sensitivity profiling in high- and low-risk groups. CONCLUSION: In summary, our study provided novel insights into the function of CRRICRGs in UCEC. We also developed a reliable prognostic panel for the survival of patients with UCEC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41065-022-00253-w.
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spelling pubmed-95782202022-10-19 A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients Liu, Zesi Yang, Hongxia Chen, Ziyu Jing, Chunli Hereditas Research BACKGROUND: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and its prevalence is increasing. As an emerging therapy with a promising efficacy, immunotherapy has been extensively applied in the treatment of solid tumors. In addition, chromatin regulators (CRs), as essential upstream regulators of epigenetics, play a significant role in tumorigenesis and cancer development. METHODS: CRs and immune checkpoint-related genes (ICRGs) were obtained from the previous top research. The Genome Cancer Atlas (TCGA) was utilized to acquire the mRNA expression and clinical information of patients with EC. Correlation analysis was utilized for screen CRs-related ICRGs (CRRICRGs). By Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, prognosis related CRRICRGs were screened out and risk model was constructed. The Kaplan–Meier curve was used to estimate the prognosis between high- and low-risk group. By comparing the IC50 value, the drugs sensitivity difference was explored. We obtained small molecule drugs for the treatment of UCEC patients based on CAMP dataset. RESULTS: We successfully constructed a 9 CRRICRs-based prognostic signature for patients with UCEC and found the riskscore was an independent prognostic factor. The results of functional analysis suggested that CRRICRGs may be involved in immune processes associated with cancer. Immune characteristics analysis provided further evidence that the CRRICRGs-based model was correlated with immune cells infiltration and immune checkpoint. Eight small molecule drugs that may be effective for the treatment of UCEC patients were screened. Effective drugs identified by drug sensitivity profiling in high- and low-risk groups. CONCLUSION: In summary, our study provided novel insights into the function of CRRICRGs in UCEC. We also developed a reliable prognostic panel for the survival of patients with UCEC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41065-022-00253-w. BioMed Central 2022-10-18 /pmc/articles/PMC9578220/ /pubmed/36253800 http://dx.doi.org/10.1186/s41065-022-00253-w 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
Liu, Zesi
Yang, Hongxia
Chen, Ziyu
Jing, Chunli
A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients
title A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients
title_full A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients
title_fullStr A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients
title_full_unstemmed A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients
title_short A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients
title_sort novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578220/
https://www.ncbi.nlm.nih.gov/pubmed/36253800
http://dx.doi.org/10.1186/s41065-022-00253-w
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