Comprehensive Analyses and Immunophenotyping of LIM Domain Family Genes in Patients with Non-Small-Cell Lung Cancer
The LIM domain family genes play a crucial role in various tumors, including non-small-cell lung cancer (NSCLC). Immunotherapy is one of the most significant treatments for NSCLC, and its effectiveness largely depends on the tumor microenvironment (TME). Currently, the potential roles of LIM domain...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/5/4524 |
| _version_ | 1797615238349062144 |
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| author | Sini Li Lihui Liu Yan Qu Li Yuan Xue Zhang Zixiao Ma Hua Bai Jie Wang |
| author_facet | Sini Li Lihui Liu Yan Qu Li Yuan Xue Zhang Zixiao Ma Hua Bai Jie Wang |
| author_sort | Sini Li |
| collection | DOAJ |
| description | The LIM domain family genes play a crucial role in various tumors, including non-small-cell lung cancer (NSCLC). Immunotherapy is one of the most significant treatments for NSCLC, and its effectiveness largely depends on the tumor microenvironment (TME). Currently, the potential roles of LIM domain family genes in the TME of NSCLC remain elusive. We comprehensively evaluated the expression and mutation patterns of 47 LIM domain family genes in 1089 NSCLC samples. Using unsupervised clustering analysis, we classified patients with NSCLC into two distinct gene clusters, i.e., the LIM-high group and the LIM-low group. We further investigated the prognosis, TME cell infiltration characteristics, and immunotherapy in the two groups. The LIM-high and LIM-low groups had different biological processes and prognoses. Moreover, there were significant differences in TME characteristics between the LIM-high and LIM-low groups. Specifically, enhanced survival, immune cell activation, and high tumor purity were demonstrated in patients of the LIM-low group, implying an immune-inflamed phenotype. Moreover, the LIM-low group had higher immune cell proportion scores than the LIM-high group and was more responsive to immunotherapy than the LIM-low group. Additionally, we screened out LIM and senescent cell antigen-like domain 1 (LIMS1) as a hub gene of the LIM domain family via five different algorithms of plug-in cytoHubba and the weighted gene co-expression network analysis. Subsequently, proliferation, migration, and invasion assays demonstrated that LIMS1 acts as a pro-tumor gene that promotes the invasion and progression of NSCLC cell lines. This is the first study to reveal a novel LIM domain family gene-related molecular pattern associated with the TME phenotype, which would increase our understanding of the heterogeneity and plasticity of the TME in NSCLC. LIMS1 may serve as a potential therapeutic target for NSCLC. |
| first_indexed | 2024-03-11T07:22:36Z |
| format | Article |
| id | doaj.art-6808120c29d44707a870dbd0ace64b1b |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T07:22:36Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6808120c29d44707a870dbd0ace64b1b2023-11-17T07:49:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01245452410.3390/ijms24054524Comprehensive Analyses and Immunophenotyping of LIM Domain Family Genes in Patients with Non-Small-Cell Lung CancerSini Li0Lihui Liu1Yan Qu2Li Yuan3Xue Zhang4Zixiao Ma5Hua Bai6Jie Wang7National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaThe LIM domain family genes play a crucial role in various tumors, including non-small-cell lung cancer (NSCLC). Immunotherapy is one of the most significant treatments for NSCLC, and its effectiveness largely depends on the tumor microenvironment (TME). Currently, the potential roles of LIM domain family genes in the TME of NSCLC remain elusive. We comprehensively evaluated the expression and mutation patterns of 47 LIM domain family genes in 1089 NSCLC samples. Using unsupervised clustering analysis, we classified patients with NSCLC into two distinct gene clusters, i.e., the LIM-high group and the LIM-low group. We further investigated the prognosis, TME cell infiltration characteristics, and immunotherapy in the two groups. The LIM-high and LIM-low groups had different biological processes and prognoses. Moreover, there were significant differences in TME characteristics between the LIM-high and LIM-low groups. Specifically, enhanced survival, immune cell activation, and high tumor purity were demonstrated in patients of the LIM-low group, implying an immune-inflamed phenotype. Moreover, the LIM-low group had higher immune cell proportion scores than the LIM-high group and was more responsive to immunotherapy than the LIM-low group. Additionally, we screened out LIM and senescent cell antigen-like domain 1 (LIMS1) as a hub gene of the LIM domain family via five different algorithms of plug-in cytoHubba and the weighted gene co-expression network analysis. Subsequently, proliferation, migration, and invasion assays demonstrated that LIMS1 acts as a pro-tumor gene that promotes the invasion and progression of NSCLC cell lines. This is the first study to reveal a novel LIM domain family gene-related molecular pattern associated with the TME phenotype, which would increase our understanding of the heterogeneity and plasticity of the TME in NSCLC. LIMS1 may serve as a potential therapeutic target for NSCLC.https://www.mdpi.com/1422-0067/24/5/4524LIM domain familyLIMS1molecular subtypesnon-small-cell lung cancertumor microenvironment |
| spellingShingle | Sini Li Lihui Liu Yan Qu Li Yuan Xue Zhang Zixiao Ma Hua Bai Jie Wang Comprehensive Analyses and Immunophenotyping of LIM Domain Family Genes in Patients with Non-Small-Cell Lung Cancer International Journal of Molecular Sciences LIM domain family LIMS1 molecular subtypes non-small-cell lung cancer tumor microenvironment |
| title | Comprehensive Analyses and Immunophenotyping of LIM Domain Family Genes in Patients with Non-Small-Cell Lung Cancer |
| title_full | Comprehensive Analyses and Immunophenotyping of LIM Domain Family Genes in Patients with Non-Small-Cell Lung Cancer |
| title_fullStr | Comprehensive Analyses and Immunophenotyping of LIM Domain Family Genes in Patients with Non-Small-Cell Lung Cancer |
| title_full_unstemmed | Comprehensive Analyses and Immunophenotyping of LIM Domain Family Genes in Patients with Non-Small-Cell Lung Cancer |
| title_short | Comprehensive Analyses and Immunophenotyping of LIM Domain Family Genes in Patients with Non-Small-Cell Lung Cancer |
| title_sort | comprehensive analyses and immunophenotyping of lim domain family genes in patients with non small cell lung cancer |
| topic | LIM domain family LIMS1 molecular subtypes non-small-cell lung cancer tumor microenvironment |
| url | https://www.mdpi.com/1422-0067/24/5/4524 |
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