FAT1 mutation-related signature predicts survival risk and tumor immunogenicity in lung adenocarcinoma
BackgroundFAT atypical cadherin 1 (FAT1) is a well-known tumor regulator that plays a crucial role in multiple cancer signaling pathways. Its mutations have been linked to tumor progression and immune regulation in various cancers, including lung adenocarcinoma (LUAD). In this study, we aim to ident...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1466484/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839643358469816320 |
|---|---|
| author | Lifeng Gao Xueying Wang Yixin Xu Aimin Wang Wenjing Zhang Qinghua Wang Yanfeng Ren |
| author_facet | Lifeng Gao Xueying Wang Yixin Xu Aimin Wang Wenjing Zhang Qinghua Wang Yanfeng Ren |
| author_sort | Lifeng Gao |
| collection | DOAJ |
| description | BackgroundFAT atypical cadherin 1 (FAT1) is a well-known tumor regulator that plays a crucial role in multiple cancer signaling pathways. Its mutations have been linked to tumor progression and immune regulation in various cancers, including lung adenocarcinoma (LUAD). In this study, we aim to identify a FAT1 mutation-related transcriptomic risk signature to assess the survival risks and immune status of LUAD patients.MethodsA total of 2528 LUAD samples, which included both gene expression profiles and clinicopathologic data, were collected from 12 datasets. Additionally, two datasets treated with immunotherapies were also included to investigate the therapeutic effects.ResultsWe constructed a FAT1 mutation molecular signature based on 9 relevant genes. LUAD patients with low-risk scores demonstrated a more favorable prognosis compared to those with high-risk scores, which is corroborated by 6 additional independent datasets. Further immunological, mutational, and intratumor microbial analyses reveal that increased infiltration of immune effector cells, increased mutational burden, specific mutational signatures (such as age and APOBEC associated), mutations in driver genes (e.g., TP53, KEAP1, NAV3, and SMARCA4), and increased microbial α/β diversities are present in the low-risk LUAD patients. Based on the immunotherapeutic patients, an improved immune checkpoint blockade treatment prognosis and an elevated response rate are also observed in the low-risk signature group.ConclusionIn summary, Our identified FAT1 mutation-related risk signature shows potential for assessing LUAD clinical outcomes, tumor immunogenicity, and immunotherapy effectiveness, providing valuable insights for LUAD clinical practice. |
| format | Article |
| id | doaj-art-a7f97a8e92554464a90dde47d0d452b7 |
| institution | Matheson Library |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj-art-a7f97a8e92554464a90dde47d0d452b72025-07-02T04:14:25ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-07-011610.3389/fgene.2025.14664841466484FAT1 mutation-related signature predicts survival risk and tumor immunogenicity in lung adenocarcinomaLifeng Gao0Xueying Wang1Yixin Xu2Aimin Wang3Wenjing Zhang4Qinghua Wang5Yanfeng Ren6Department of Clinical Laboratory, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, ChinaKey Laboratory of Medicine and Health of Shandong Province, Department of Health Statistics, School of Public Health, Shandong Second Medical University, Weifang, Shandong, ChinaSchool of Medical Laboratory, Shandong Second Medical University, Weifang, Shandong, ChinaKey Laboratory of Medicine and Health of Shandong Province, Department of Health Statistics, School of Public Health, Shandong Second Medical University, Weifang, Shandong, ChinaKey Laboratory of Medicine and Health of Shandong Province, Department of Health Statistics, School of Public Health, Shandong Second Medical University, Weifang, Shandong, ChinaKey Laboratory of Medicine and Health of Shandong Province, Department of Health Statistics, School of Public Health, Shandong Second Medical University, Weifang, Shandong, ChinaKey Laboratory of Medicine and Health of Shandong Province, Department of Health Statistics, School of Public Health, Shandong Second Medical University, Weifang, Shandong, ChinaBackgroundFAT atypical cadherin 1 (FAT1) is a well-known tumor regulator that plays a crucial role in multiple cancer signaling pathways. Its mutations have been linked to tumor progression and immune regulation in various cancers, including lung adenocarcinoma (LUAD). In this study, we aim to identify a FAT1 mutation-related transcriptomic risk signature to assess the survival risks and immune status of LUAD patients.MethodsA total of 2528 LUAD samples, which included both gene expression profiles and clinicopathologic data, were collected from 12 datasets. Additionally, two datasets treated with immunotherapies were also included to investigate the therapeutic effects.ResultsWe constructed a FAT1 mutation molecular signature based on 9 relevant genes. LUAD patients with low-risk scores demonstrated a more favorable prognosis compared to those with high-risk scores, which is corroborated by 6 additional independent datasets. Further immunological, mutational, and intratumor microbial analyses reveal that increased infiltration of immune effector cells, increased mutational burden, specific mutational signatures (such as age and APOBEC associated), mutations in driver genes (e.g., TP53, KEAP1, NAV3, and SMARCA4), and increased microbial α/β diversities are present in the low-risk LUAD patients. Based on the immunotherapeutic patients, an improved immune checkpoint blockade treatment prognosis and an elevated response rate are also observed in the low-risk signature group.ConclusionIn summary, Our identified FAT1 mutation-related risk signature shows potential for assessing LUAD clinical outcomes, tumor immunogenicity, and immunotherapy effectiveness, providing valuable insights for LUAD clinical practice.https://www.frontiersin.org/articles/10.3389/fgene.2025.1466484/fulllung adenocarcinomaFAT1 mutation signaturesurvival risktumor immunogenicityimmune treatmentprognostic indicators |
| spellingShingle | Lifeng Gao Xueying Wang Yixin Xu Aimin Wang Wenjing Zhang Qinghua Wang Yanfeng Ren FAT1 mutation-related signature predicts survival risk and tumor immunogenicity in lung adenocarcinoma Frontiers in Genetics lung adenocarcinoma FAT1 mutation signature survival risk tumor immunogenicity immune treatment prognostic indicators |
| title | FAT1 mutation-related signature predicts survival risk and tumor immunogenicity in lung adenocarcinoma |
| title_full | FAT1 mutation-related signature predicts survival risk and tumor immunogenicity in lung adenocarcinoma |
| title_fullStr | FAT1 mutation-related signature predicts survival risk and tumor immunogenicity in lung adenocarcinoma |
| title_full_unstemmed | FAT1 mutation-related signature predicts survival risk and tumor immunogenicity in lung adenocarcinoma |
| title_short | FAT1 mutation-related signature predicts survival risk and tumor immunogenicity in lung adenocarcinoma |
| title_sort | fat1 mutation related signature predicts survival risk and tumor immunogenicity in lung adenocarcinoma |
| topic | lung adenocarcinoma FAT1 mutation signature survival risk tumor immunogenicity immune treatment prognostic indicators |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1466484/full |
| work_keys_str_mv | AT lifenggao fat1mutationrelatedsignaturepredictssurvivalriskandtumorimmunogenicityinlungadenocarcinoma AT xueyingwang fat1mutationrelatedsignaturepredictssurvivalriskandtumorimmunogenicityinlungadenocarcinoma AT yixinxu fat1mutationrelatedsignaturepredictssurvivalriskandtumorimmunogenicityinlungadenocarcinoma AT aiminwang fat1mutationrelatedsignaturepredictssurvivalriskandtumorimmunogenicityinlungadenocarcinoma AT wenjingzhang fat1mutationrelatedsignaturepredictssurvivalriskandtumorimmunogenicityinlungadenocarcinoma AT qinghuawang fat1mutationrelatedsignaturepredictssurvivalriskandtumorimmunogenicityinlungadenocarcinoma AT yanfengren fat1mutationrelatedsignaturepredictssurvivalriskandtumorimmunogenicityinlungadenocarcinoma |