Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer

Ovarian cancer (OC) is the deadliest malignancy in gynecology, but the mechanism of its initiation and progression is poorly elucidated. Disulfidptosis is a novel discovered type of regulatory cell death. This study aimed to develop a novel disulfidptosis-related prognostic signature (DRPS) for OC a...

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Published inFrontiers in genetics Vol. 15; p. 1378907
Main Authors Cong, Yunyan, Cai, Guangyao, Ding, Chengcheng, Zhang, Han, Chen, Jieping, Luo, Shiwei, Liu, Jihong
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 17.04.2024
Subjects
biomarker
disulfidptosis
Genetics
ovarian cancer
prognosis
treatment
treatment
biomarker
ovarian cancer
disulfidptosis
prognosis
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Abstract Ovarian cancer (OC) is the deadliest malignancy in gynecology, but the mechanism of its initiation and progression is poorly elucidated. Disulfidptosis is a novel discovered type of regulatory cell death. This study aimed to develop a novel disulfidptosis-related prognostic signature (DRPS) for OC and explore the effects and potential treatment by disulfidptosis-related risk stratification. The disulfidptosis-related genes were first analyzed in bulk RNA-Seq and a prognostic nomogram was developed and validated by LASSO algorithm and multivariate cox regression. Then we systematically assessed the clinicopathological and mutational characteristics, pathway enrichment analysis, immune cell infiltration, single-cell-level expression, and drug sensitivity according to DRPS. The DRPS was established with 6 genes (MYL6, PDLIM1, ACTN4, FLNB, SLC7A11, and CD2AP) and the corresponding prognostic nomogram was constructed based on the DRPS, FIGO stage, grade, and residual disease. Stratified by the risk score derived from DRPS, patients in high-risk group tended to have worse prognosis, lower level of disulfidptosis, activated oncogenic pathways, inhibitory tumor immune microenvironment, and higher sensitivity to specific drugs including epirubicin, stauroporine, navitoclax, and tamoxifen. Single-cell transcriptomic analysis revealed the expression level of genes in the DRPS significantly varied in different cell types between tumor and normal tissues. The protein-level expression of genes in the DRPS was validated by the immunohistochemical staining analysis. In this study, the DRPS and corresponding prognostic nomogram for OC were developed, which was important for OC prognostic assessment, tumor microenvironment modification, drug sensitivity prediction, and exploration of potential mechanisms in tumor development.
AbstractList Introduction:Ovarian cancer (OC) is the deadliest malignancy in gynecology, but the mechanism of its initiation and progression is poorly elucidated. Disulfidptosis is a novel discovered type of regulatory cell death. This study aimed to develop a novel disulfidptosis-related prognostic signature (DRPS) for OC and explore the effects and potential treatment by disulfidptosis-related risk stratification.Methods:The disulfidptosis-related genes were first analyzed in bulk RNA-Seq and a prognostic nomogram was developed and validated by LASSO algorithm and multivariate cox regression. Then we systematically assessed the clinicopathological and mutational characteristics, pathway enrichment analysis, immune cell infiltration, single-cell-level expression, and drug sensitivity according to DRPS.Results:The DRPS was established with 6 genes (MYL6, PDLIM1, ACTN4, FLNB, SLC7A11, and CD2AP) and the corresponding prognostic nomogram was constructed based on the DRPS, FIGO stage, grade, and residual disease. Stratified by the risk score derived from DRPS, patients in high-risk group tended to have worse prognosis, lower level of disulfidptosis, activated oncogenic pathways, inhibitory tumor immune microenvironment, and higher sensitivity to specific drugs including epirubicin, stauroporine, navitoclax, and tamoxifen. Single-cell transcriptomic analysis revealed the expression level of genes in the DRPS significantly varied in different cell types between tumor and normal tissues. The protein-level expression of genes in the DRPS was validated by the immunohistochemical staining analysis.Conclusion:In this study, the DRPS and corresponding prognostic nomogram for OC were developed, which was important for OC prognostic assessment, tumor microenvironment modification, drug sensitivity prediction, and exploration of potential mechanisms in tumor development.
Ovarian cancer (OC) is the deadliest malignancy in gynecology, but the mechanism of its initiation and progression is poorly elucidated. Disulfidptosis is a novel discovered type of regulatory cell death. This study aimed to develop a novel disulfidptosis-related prognostic signature (DRPS) for OC and explore the effects and potential treatment by disulfidptosis-related risk stratification. The disulfidptosis-related genes were first analyzed in bulk RNA-Seq and a prognostic nomogram was developed and validated by LASSO algorithm and multivariate cox regression. Then we systematically assessed the clinicopathological and mutational characteristics, pathway enrichment analysis, immune cell infiltration, single-cell-level expression, and drug sensitivity according to DRPS. The DRPS was established with 6 genes (MYL6, PDLIM1, ACTN4, FLNB, SLC7A11, and CD2AP) and the corresponding prognostic nomogram was constructed based on the DRPS, FIGO stage, grade, and residual disease. Stratified by the risk score derived from DRPS, patients in high-risk group tended to have worse prognosis, lower level of disulfidptosis, activated oncogenic pathways, inhibitory tumor immune microenvironment, and higher sensitivity to specific drugs including epirubicin, stauroporine, navitoclax, and tamoxifen. Single-cell transcriptomic analysis revealed the expression level of genes in the DRPS significantly varied in different cell types between tumor and normal tissues. The protein-level expression of genes in the DRPS was validated by the immunohistochemical staining analysis. In this study, the DRPS and corresponding prognostic nomogram for OC were developed, which was important for OC prognostic assessment, tumor microenvironment modification, drug sensitivity prediction, and exploration of potential mechanisms in tumor development.
Ovarian cancer (OC) is the deadliest malignancy in gynecology, but the mechanism of its initiation and progression is poorly elucidated. Disulfidptosis is a novel discovered type of regulatory cell death. This study aimed to develop a novel disulfidptosis-related prognostic signature (DRPS) for OC and explore the effects and potential treatment by disulfidptosis-related risk stratification.IntroductionOvarian cancer (OC) is the deadliest malignancy in gynecology, but the mechanism of its initiation and progression is poorly elucidated. Disulfidptosis is a novel discovered type of regulatory cell death. This study aimed to develop a novel disulfidptosis-related prognostic signature (DRPS) for OC and explore the effects and potential treatment by disulfidptosis-related risk stratification.The disulfidptosis-related genes were first analyzed in bulk RNA-Seq and a prognostic nomogram was developed and validated by LASSO algorithm and multivariate cox regression. Then we systematically assessed the clinicopathological and mutational characteristics, pathway enrichment analysis, immune cell infiltration, single-cell-level expression, and drug sensitivity according to DRPS.MethodsThe disulfidptosis-related genes were first analyzed in bulk RNA-Seq and a prognostic nomogram was developed and validated by LASSO algorithm and multivariate cox regression. Then we systematically assessed the clinicopathological and mutational characteristics, pathway enrichment analysis, immune cell infiltration, single-cell-level expression, and drug sensitivity according to DRPS.The DRPS was established with 6 genes (MYL6, PDLIM1, ACTN4, FLNB, SLC7A11, and CD2AP) and the corresponding prognostic nomogram was constructed based on the DRPS, FIGO stage, grade, and residual disease. Stratified by the risk score derived from DRPS, patients in high-risk group tended to have worse prognosis, lower level of disulfidptosis, activated oncogenic pathways, inhibitory tumor immune microenvironment, and higher sensitivity to specific drugs including epirubicin, stauroporine, navitoclax, and tamoxifen. Single-cell transcriptomic analysis revealed the expression level of genes in the DRPS significantly varied in different cell types between tumor and normal tissues. The protein-level expression of genes in the DRPS was validated by the immunohistochemical staining analysis.ResultsThe DRPS was established with 6 genes (MYL6, PDLIM1, ACTN4, FLNB, SLC7A11, and CD2AP) and the corresponding prognostic nomogram was constructed based on the DRPS, FIGO stage, grade, and residual disease. Stratified by the risk score derived from DRPS, patients in high-risk group tended to have worse prognosis, lower level of disulfidptosis, activated oncogenic pathways, inhibitory tumor immune microenvironment, and higher sensitivity to specific drugs including epirubicin, stauroporine, navitoclax, and tamoxifen. Single-cell transcriptomic analysis revealed the expression level of genes in the DRPS significantly varied in different cell types between tumor and normal tissues. The protein-level expression of genes in the DRPS was validated by the immunohistochemical staining analysis.In this study, the DRPS and corresponding prognostic nomogram for OC were developed, which was important for OC prognostic assessment, tumor microenvironment modification, drug sensitivity prediction, and exploration of potential mechanisms in tumor development.ConclusionIn this study, the DRPS and corresponding prognostic nomogram for OC were developed, which was important for OC prognostic assessment, tumor microenvironment modification, drug sensitivity prediction, and exploration of potential mechanisms in tumor development.
Author Cong, Yunyan
Ding, Chengcheng
Chen, Jieping
Zhang, Han
Luo, Shiwei
Cai, Guangyao
Liu, Jihong
AuthorAffiliation 2 Department of Gynecologic Oncology , State Key Laboratory of Oncology in South China , Guangdong Provincial Clinical Research Center for Cancer , Sun Yat-Sen University Cancer Center , Guangzhou , China
3 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases , Guangzhou , China
4 Department of Obstetrics and Gynecology , The First Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China
1 Department of Oncology , The Fifth Affiliated Hospital of Sun Yat-Sen University , Zhuhai , China
AuthorAffiliation_xml – name: 3 Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases , Guangzhou , China
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– name: 2 Department of Gynecologic Oncology , State Key Laboratory of Oncology in South China , Guangdong Provincial Clinical Research Center for Cancer , Sun Yat-Sen University Cancer Center , Guangzhou , China
– name: 4 Department of Obstetrics and Gynecology , The First Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China
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CitedBy_id crossref_primary_10_3389_fendo_2024_1434705
crossref_primary_10_1007_s12672_024_01489_w
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Keywords treatment
biomarker
ovarian cancer
disulfidptosis
prognosis
Language English
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Xiaoshu Zhou, Huazhong University of Science and Technology, China
Edited by: Mehdi Pirooznia, Johnson & Johnson, United States
These authors have contributed equally to this work
Reviewed by: Raj Kumar Mongre, Harvard Medical School, United States
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Snippet Ovarian cancer (OC) is the deadliest malignancy in gynecology, but the mechanism of its initiation and progression is poorly elucidated. Disulfidptosis is a...
Introduction:Ovarian cancer (OC) is the deadliest malignancy in gynecology, but the mechanism of its initiation and progression is poorly elucidated....
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SubjectTerms biomarker
disulfidptosis
Genetics
ovarian cancer
prognosis
treatment
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Title Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer
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