Establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis/ferroptosis-associated signature
BackgroundDisulfidptosis and ferroptosis are two different programmed cell death pathways, and their potential therapeutic targets have important clinical prospects. Although there is an association between the two, the role of genes associated with these two forms of cell death in the development o...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1492541/full |
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| author | Yong Huang Huibin Li Zhifu Wei Wanshan He Bin Chen Shuang Cheng Zhifang Zhao Lv Deng Lv Deng Xiaohua Chen Yu Lin Yu Lin Xiaoshan Hong Xiaoshan Hong |
| author_facet | Yong Huang Huibin Li Zhifu Wei Wanshan He Bin Chen Shuang Cheng Zhifang Zhao Lv Deng Lv Deng Xiaohua Chen Yu Lin Yu Lin Xiaoshan Hong Xiaoshan Hong |
| author_sort | Yong Huang |
| collection | DOAJ |
| description | BackgroundDisulfidptosis and ferroptosis are two different programmed cell death pathways, and their potential therapeutic targets have important clinical prospects. Although there is an association between the two, the role of genes associated with these two forms of cell death in the development of endometrial cancer remains unclear.MethodsIn this study, RNA sequencing (RNA-seq) and clinical data were obtained from public databases, and comprehensive analysis methods, including difference analysis, univariate Cox regression, and Least Absolute Shrinkage and Selection Operator (LASSO) analysis were used to construct a disulfidptosis/ferroptosis-related genes (DFRGs) prognostic signature. To further explore this new feature, pathway and functional analyses were performed, and the differences in gene mutation frequency and the level of immune cell infiltration between the high- and low-risk groups were studied. Finally, we validated the prognostic gene expression profile in clinical samples.ResultsWe identified five optimal DFRGs that were differentially expressed and associated with the prognosis of uterine corpus endometrial carcinoma (UCEC). These genes include CDKN2A, FZD7, LCN2, ACTN4, and MYH10. Based on these DFRGs, we constructed a robust prognostic model with significantly lower overall survival in the high-risk group than in the low-risk group, with differences in tumor burden and immune invasion between the different risk groups. The expression of two key genes, ACTN4 and LCN2, was verified by immunohistochemistry and RT-qPCR.ConclusionThis study established a clinical prognostic model associated with disulfidptosis/ferroptosis-related genes, and the expression characteristics of key genes were validated in clinical samples. The comprehensive assessment of disulfidptosis and ferroptosis provides new insights to further guide patient clinical management and personalized treatment. |
| format | Article |
| id | doaj-art-34112027cad7486ab1f16e3e63d9e89e |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-34112027cad7486ab1f16e3e63d9e89e2025-01-27T06:40:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.14925411492541Establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis/ferroptosis-associated signatureYong Huang0Huibin Li1Zhifu Wei2Wanshan He3Bin Chen4Shuang Cheng5Zhifang Zhao6Lv Deng7Lv Deng8Xiaohua Chen9Yu Lin10Yu Lin11Xiaoshan Hong12Xiaoshan Hong13Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Pathology, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Gynecology, The Affiliated Shunde Hospital of Jinan University, Foshan, ChinaDepartment of Gynecology, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Gynecology, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Gastroenterology, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Gastroenterology, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Gastroenterology, People’s Hospital of Rongjiang County, Rongjiang, ChinaDepartment of Gastroenterology, People’s Hospital of Nanhai District, Foshan, ChinaOncology Center, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaNanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Gastroenterology, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Gynecology, Guangdong Women and Children Hospital, Guangzhou, China0Department of Gynecology, Qingxin District Hospital of Women and Children Healthcare, Qingyuan, ChinaBackgroundDisulfidptosis and ferroptosis are two different programmed cell death pathways, and their potential therapeutic targets have important clinical prospects. Although there is an association between the two, the role of genes associated with these two forms of cell death in the development of endometrial cancer remains unclear.MethodsIn this study, RNA sequencing (RNA-seq) and clinical data were obtained from public databases, and comprehensive analysis methods, including difference analysis, univariate Cox regression, and Least Absolute Shrinkage and Selection Operator (LASSO) analysis were used to construct a disulfidptosis/ferroptosis-related genes (DFRGs) prognostic signature. To further explore this new feature, pathway and functional analyses were performed, and the differences in gene mutation frequency and the level of immune cell infiltration between the high- and low-risk groups were studied. Finally, we validated the prognostic gene expression profile in clinical samples.ResultsWe identified five optimal DFRGs that were differentially expressed and associated with the prognosis of uterine corpus endometrial carcinoma (UCEC). These genes include CDKN2A, FZD7, LCN2, ACTN4, and MYH10. Based on these DFRGs, we constructed a robust prognostic model with significantly lower overall survival in the high-risk group than in the low-risk group, with differences in tumor burden and immune invasion between the different risk groups. The expression of two key genes, ACTN4 and LCN2, was verified by immunohistochemistry and RT-qPCR.ConclusionThis study established a clinical prognostic model associated with disulfidptosis/ferroptosis-related genes, and the expression characteristics of key genes were validated in clinical samples. The comprehensive assessment of disulfidptosis and ferroptosis provides new insights to further guide patient clinical management and personalized treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1492541/fullUCECuterine corpus endometrial carcinomadisulfidptosisferroptosisprognostic signatureimmune infiltration |
| spellingShingle | Yong Huang Huibin Li Zhifu Wei Wanshan He Bin Chen Shuang Cheng Zhifang Zhao Lv Deng Lv Deng Xiaohua Chen Yu Lin Yu Lin Xiaoshan Hong Xiaoshan Hong Establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis/ferroptosis-associated signature Frontiers in Immunology UCEC uterine corpus endometrial carcinoma disulfidptosis ferroptosis prognostic signature immune infiltration |
| title | Establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis/ferroptosis-associated signature |
| title_full | Establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis/ferroptosis-associated signature |
| title_fullStr | Establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis/ferroptosis-associated signature |
| title_full_unstemmed | Establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis/ferroptosis-associated signature |
| title_short | Establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis/ferroptosis-associated signature |
| title_sort | establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis ferroptosis associated signature |
| topic | UCEC uterine corpus endometrial carcinoma disulfidptosis ferroptosis prognostic signature immune infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1492541/full |
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