Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer
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 (D...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1378907/full |
| _version_ | 1797202933170831360 |
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| author | Yunyan Cong Yunyan Cong Yunyan Cong Guangyao Cai Guangyao Cai Chengcheng Ding Chengcheng Ding Chengcheng Ding Han Zhang Han Zhang Jieping Chen Jieping Chen Shiwei Luo Shiwei Luo Jihong Liu Jihong Liu |
| author_facet | Yunyan Cong Yunyan Cong Yunyan Cong Guangyao Cai Guangyao Cai Chengcheng Ding Chengcheng Ding Chengcheng Ding Han Zhang Han Zhang Jieping Chen Jieping Chen Shiwei Luo Shiwei Luo Jihong Liu Jihong Liu |
| author_sort | Yunyan Cong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T08:11:18Z |
| format | Article |
| id | doaj.art-239d400b722444a6807ed0e640883878 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-24T08:11:18Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-239d400b722444a6807ed0e6408838782024-04-17T04:56:37ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-04-011510.3389/fgene.2024.13789071378907Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancerYunyan Cong0Yunyan Cong1Yunyan Cong2Guangyao Cai3Guangyao Cai4Chengcheng Ding5Chengcheng Ding6Chengcheng Ding7Han Zhang8Han Zhang9Jieping Chen10Jieping Chen11Shiwei Luo12Shiwei Luo13Jihong Liu14Jihong Liu15Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment 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, ChinaGuangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, ChinaDepartment 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, ChinaGuangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, ChinaDepartment 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, ChinaGuangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaDepartment 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, ChinaGuangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, ChinaDepartment 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, ChinaGuangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, ChinaDepartment 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, ChinaGuangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, ChinaDepartment 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, ChinaGuangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, ChinaIntroduction: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.https://www.frontiersin.org/articles/10.3389/fgene.2024.1378907/fulldisulfidptosisovarian cancerprognosistreatmentbiomarker |
| spellingShingle | Yunyan Cong Yunyan Cong Yunyan Cong Guangyao Cai Guangyao Cai Chengcheng Ding Chengcheng Ding Chengcheng Ding Han Zhang Han Zhang Jieping Chen Jieping Chen Shiwei Luo Shiwei Luo Jihong Liu Jihong Liu Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer Frontiers in Genetics disulfidptosis ovarian cancer prognosis treatment biomarker |
| title | Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer |
| title_full | Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer |
| title_fullStr | Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer |
| title_full_unstemmed | Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer |
| title_short | Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer |
| title_sort | disulfidptosis related signature elucidates the prognostic immunologic and therapeutic characteristics in ovarian cancer |
| topic | disulfidptosis ovarian cancer prognosis treatment biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1378907/full |
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