SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinoma
IntroductionLung adenocarcinoma (LUAD) is a prevalent form of lung cancer originating from lung glandular cells with low survival rates despite recent therapeutic advances due to its diverse and complex nature. Recent evidence suggests a link between ferroptosis and the effectiveness of anti-PD-L1 t...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1372215/full |
| _version_ | 1797217066462216192 |
|---|---|
| author | Zhenyao Huang Zhenyao Huang Xia Chen Yun Wang Jiali Yuan Jing Li Wenlu Hang Hao Meng |
| author_facet | Zhenyao Huang Zhenyao Huang Xia Chen Yun Wang Jiali Yuan Jing Li Wenlu Hang Hao Meng |
| author_sort | Zhenyao Huang |
| collection | DOAJ |
| description | IntroductionLung adenocarcinoma (LUAD) is a prevalent form of lung cancer originating from lung glandular cells with low survival rates despite recent therapeutic advances due to its diverse and complex nature. Recent evidence suggests a link between ferroptosis and the effectiveness of anti-PD-L1 therapy, with potential synergistic effects.MethodsOur study comprehensively analyzed the expression patterns of ferroptosis regulators in LUAD and their association with prognosis and PD-L1 expression. Furthermore, we identified two distinct subtypes of LUAD through consensus clustering of ferroptosis regulators, revealing significant tumor heterogeneity, divergent PD-L1 expression, and varying prognoses between the subtypes.ResultsAmong the selected ferroptosis regulators, SLC7A11 emerged as an independent prognostic marker for LUAD patients and exhibited a negative correlation with PD-L1 expression. Subsequent investigations revealed high expression of SLC7A11 in the LUAD population. In vitro experiments demonstrated that overexpression of SLC7A11 led to reduced PD-L1 expression and inhibited ferroptosis in A549 cells, underscoring the significant role of SLC7A11 in LUAD. Additionally, pan-cancer analyses indicated an association between SLC7A11 and the expression of immune checkpoint genes across multiple cancer types with poor prognoses.DiscussionFrom a clinical standpoint, these findings offer a foundation for identifying and optimizing potential combination strategies to enhance the therapeutic effectiveness of immune checkpoint inhibitors and improve the prognosis of patients with LUAD. |
| first_indexed | 2024-04-24T11:55:57Z |
| format | Article |
| id | doaj.art-da796e1c3d1143fab84eb8f253b0c9be |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T11:55:57Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-da796e1c3d1143fab84eb8f253b0c9be2024-04-09T04:28:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-04-011510.3389/fimmu.2024.13722151372215SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinomaZhenyao Huang0Zhenyao Huang1Xia Chen2Yun Wang3Jiali Yuan4Jing Li5Wenlu Hang6Hao Meng7Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaKey Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, ChinaDepartment of Respiratory Medicine, Xuyi People’s Hospital, Huai’an, Jiangsu, ChinaDepartment of Dermatology, the Affiliated Huai'an Hospital of Xuzhou Medical University, the Second People's Hospital of Huai’an, Huai’an, ChinaKey Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, ChinaKey Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, ChinaDepartment of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaIntroductionLung adenocarcinoma (LUAD) is a prevalent form of lung cancer originating from lung glandular cells with low survival rates despite recent therapeutic advances due to its diverse and complex nature. Recent evidence suggests a link between ferroptosis and the effectiveness of anti-PD-L1 therapy, with potential synergistic effects.MethodsOur study comprehensively analyzed the expression patterns of ferroptosis regulators in LUAD and their association with prognosis and PD-L1 expression. Furthermore, we identified two distinct subtypes of LUAD through consensus clustering of ferroptosis regulators, revealing significant tumor heterogeneity, divergent PD-L1 expression, and varying prognoses between the subtypes.ResultsAmong the selected ferroptosis regulators, SLC7A11 emerged as an independent prognostic marker for LUAD patients and exhibited a negative correlation with PD-L1 expression. Subsequent investigations revealed high expression of SLC7A11 in the LUAD population. In vitro experiments demonstrated that overexpression of SLC7A11 led to reduced PD-L1 expression and inhibited ferroptosis in A549 cells, underscoring the significant role of SLC7A11 in LUAD. Additionally, pan-cancer analyses indicated an association between SLC7A11 and the expression of immune checkpoint genes across multiple cancer types with poor prognoses.DiscussionFrom a clinical standpoint, these findings offer a foundation for identifying and optimizing potential combination strategies to enhance the therapeutic effectiveness of immune checkpoint inhibitors and improve the prognosis of patients with LUAD.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1372215/fullferroptosisLUADPD-L1SLC7A11immune cell infiltration |
| spellingShingle | Zhenyao Huang Zhenyao Huang Xia Chen Yun Wang Jiali Yuan Jing Li Wenlu Hang Hao Meng SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinoma Frontiers in Immunology ferroptosis LUAD PD-L1 SLC7A11 immune cell infiltration |
| title | SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinoma |
| title_full | SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinoma |
| title_fullStr | SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinoma |
| title_full_unstemmed | SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinoma |
| title_short | SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinoma |
| title_sort | slc7a11 inhibits ferroptosis and downregulates pd l1 levels in lung adenocarcinoma |
| topic | ferroptosis LUAD PD-L1 SLC7A11 immune cell infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1372215/full |
| work_keys_str_mv | AT zhenyaohuang slc7a11inhibitsferroptosisanddownregulatespdl1levelsinlungadenocarcinoma AT zhenyaohuang slc7a11inhibitsferroptosisanddownregulatespdl1levelsinlungadenocarcinoma AT xiachen slc7a11inhibitsferroptosisanddownregulatespdl1levelsinlungadenocarcinoma AT yunwang slc7a11inhibitsferroptosisanddownregulatespdl1levelsinlungadenocarcinoma AT jialiyuan slc7a11inhibitsferroptosisanddownregulatespdl1levelsinlungadenocarcinoma AT jingli slc7a11inhibitsferroptosisanddownregulatespdl1levelsinlungadenocarcinoma AT wenluhang slc7a11inhibitsferroptosisanddownregulatespdl1levelsinlungadenocarcinoma AT haomeng slc7a11inhibitsferroptosisanddownregulatespdl1levelsinlungadenocarcinoma |