Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan‐cancer analysis
Abstract Objectives Lymphocyte activation gene 3 (LAG3), an inhibitory receptor in T‐cell activation, is a negative prognostic factor. However, its impact on tumours has yet to be comprehensively elucidated on a pan‐cancer scale. Thus, we aim to reveal its role at the pan‐cancer level. Methods We pe...
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| Format: | Article |
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Wiley
2024-01-01
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| Series: | Clinical & Translational Immunology |
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| Online Access: | https://doi.org/10.1002/cti2.70009 |
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| author | Yifan Liu Yuntao Yao Xinyue Yang Maodong Wei Bingnan Lu Keqing Dong Donghao Lyu Yuanan Li Wenbin Guan Runzhi Huang Guofeng Xu Xiuwu Pan |
| author_facet | Yifan Liu Yuntao Yao Xinyue Yang Maodong Wei Bingnan Lu Keqing Dong Donghao Lyu Yuanan Li Wenbin Guan Runzhi Huang Guofeng Xu Xiuwu Pan |
| author_sort | Yifan Liu |
| collection | DOAJ |
| description | Abstract Objectives Lymphocyte activation gene 3 (LAG3), an inhibitory receptor in T‐cell activation, is a negative prognostic factor. However, its impact on tumours has yet to be comprehensively elucidated on a pan‐cancer scale. Thus, we aim to reveal its role at the pan‐cancer level. Methods We performed IHC staining on a retrospective cohort of 370 patients. Then we assessed the prognostic effect of LAG3 using Kaplan–Meier survival analysis and multivariate Cox regression analysis. In pan‐cancer analysis, we constructed competing endogenous RNA and protein–protein interaction networks, conducted gene set enrichment analysis and identified correlations between LAG3 gene expression and various factors, including clinical characteristics, tumour purity, mutations, tumour immunity and drug sensitivity across 33 cancer types. Results LAG3 was expressed higher in normal kidney tissues than in tumours. A high level of LAG3 gene expression was an independent prognostic factor for OS (HR = 6.60, 95% CI = 2.43–17.90, P < 0.001) and PFS (HR = 3.44, 95% CI = 1.68–7.10, P < 0.001). In pan‐cancer analysis, LAG3 exhibited robust correlations with survival and tumour stages in various cancers. Moreover, LAG3 was strongly associated with immune‐related genes, proteins and signalling pathways. LAG3 gene expression was positively associated with increased infiltration of activated immune cells and decreased infiltration of several resting cells. LAG3 gene expression was associated with tumour mutation burden and microsatellite instability in multiple cancers. Conclusion High LAG3 gene expression was an independent risk factor in kidney neoplasms. It also functioned as a biomarker for prognosis, TIME and immunotherapy efficacy in the pan‐cancer dimension. |
| format | Article |
| id | doaj-art-ba0c2f73904a4fa3a3ce45ed65970862 |
| institution | OA Journals |
| issn | 2050-0068 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj-art-ba0c2f73904a4fa3a3ce45ed659708622025-08-20T02:11:24ZengWileyClinical & Translational Immunology2050-00682024-01-011310n/an/a10.1002/cti2.70009Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan‐cancer analysisYifan Liu0Yuntao Yao1Xinyue Yang2Maodong Wei3Bingnan Lu4Keqing Dong5Donghao Lyu6Yuanan Li7Wenbin Guan8Runzhi Huang9Guofeng Xu10Xiuwu Pan11Department of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Pathology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Burn Surgery The First Affiliated Hospital of Naval Medical University Shanghai ChinaDepartment of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai ChinaAbstract Objectives Lymphocyte activation gene 3 (LAG3), an inhibitory receptor in T‐cell activation, is a negative prognostic factor. However, its impact on tumours has yet to be comprehensively elucidated on a pan‐cancer scale. Thus, we aim to reveal its role at the pan‐cancer level. Methods We performed IHC staining on a retrospective cohort of 370 patients. Then we assessed the prognostic effect of LAG3 using Kaplan–Meier survival analysis and multivariate Cox regression analysis. In pan‐cancer analysis, we constructed competing endogenous RNA and protein–protein interaction networks, conducted gene set enrichment analysis and identified correlations between LAG3 gene expression and various factors, including clinical characteristics, tumour purity, mutations, tumour immunity and drug sensitivity across 33 cancer types. Results LAG3 was expressed higher in normal kidney tissues than in tumours. A high level of LAG3 gene expression was an independent prognostic factor for OS (HR = 6.60, 95% CI = 2.43–17.90, P < 0.001) and PFS (HR = 3.44, 95% CI = 1.68–7.10, P < 0.001). In pan‐cancer analysis, LAG3 exhibited robust correlations with survival and tumour stages in various cancers. Moreover, LAG3 was strongly associated with immune‐related genes, proteins and signalling pathways. LAG3 gene expression was positively associated with increased infiltration of activated immune cells and decreased infiltration of several resting cells. LAG3 gene expression was associated with tumour mutation burden and microsatellite instability in multiple cancers. Conclusion High LAG3 gene expression was an independent risk factor in kidney neoplasms. It also functioned as a biomarker for prognosis, TIME and immunotherapy efficacy in the pan‐cancer dimension.https://doi.org/10.1002/cti2.70009biomarkerkidney neoplasmLAG3pan‐cancer analysisretrospective clinical study |
| spellingShingle | Yifan Liu Yuntao Yao Xinyue Yang Maodong Wei Bingnan Lu Keqing Dong Donghao Lyu Yuanan Li Wenbin Guan Runzhi Huang Guofeng Xu Xiuwu Pan Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan‐cancer analysis Clinical & Translational Immunology biomarker kidney neoplasm LAG3 pan‐cancer analysis retrospective clinical study |
| title | Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan‐cancer analysis |
| title_full | Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan‐cancer analysis |
| title_fullStr | Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan‐cancer analysis |
| title_full_unstemmed | Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan‐cancer analysis |
| title_short | Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan‐cancer analysis |
| title_sort | lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types a clinical and pan cancer analysis |
| topic | biomarker kidney neoplasm LAG3 pan‐cancer analysis retrospective clinical study |
| url | https://doi.org/10.1002/cti2.70009 |
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