Identification and Validation of <i>RELN</i> Mutation as a Response Indicator for Immune Checkpoint Inhibitor Therapy in Melanoma and Non-Small Cell Lung Cancer
Remarkable clinical benefits in several advanced cancers are observed under the treatment of immune checkpoint inhibitor (ICI) agents. However, only a smaller proportion of patients respond to the treatments. Reelin (RELN) is frequently mutated in the cancer genome. In this study, the <i>RELN&...
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MDPI AG
2022-11-01
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| author | Zhenpeng Li Xin Wang Yi Yang Fuyan Shi Wenjing Zhang Qinghua Wang Suzhen Wang |
| author_facet | Zhenpeng Li Xin Wang Yi Yang Fuyan Shi Wenjing Zhang Qinghua Wang Suzhen Wang |
| author_sort | Zhenpeng Li |
| collection | DOAJ |
| description | Remarkable clinical benefits in several advanced cancers are observed under the treatment of immune checkpoint inhibitor (ICI) agents. However, only a smaller proportion of patients respond to the treatments. Reelin (RELN) is frequently mutated in the cancer genome. In this study, the <i>RELN</i> mutation association with ICI treatment efficacy in melanoma and non-small cell lung cancer (NSCLC) was elucidated. Data from 631 melanoma and 109 NSCLC patients with both ICI treatment data and pre-treatment mutational profiles were collected. In addition, from the Cancer Genome Atlas (TCGA) project, we also obtained both tumors to explore the immunologic features behind <i>RELN</i> mutations. Melanoma patients with <i>RELN</i> mutations exhibited a favorable ICI survival benefit when compared with wild-type patients (HR: 0.66, 95% CI: 0.51–0.87, <i>p</i> = 0.003). A higher response rate was also noticed in <i>RELN</i>-mutated patients (38.9% vs. 28.3%, <i>p</i> = 0.017). The association of <i>RELN</i> mutations with a preferable immunotherapy outcome and response was further confirmed in NSCLC. Further exploration demonstrated that favorable immunocyte infiltration and immune response signaling pathways were found in patients with <i>RELN</i> mutations. In this study, <i>RELN</i> mutations were identified to connect with a better immune microenvironment and an improved ICI efficacy in melanoma and NSCLC, which provides a potential biomarker for immunological feature evaluation and immunotherapeutic outcome prediction at the molecular level. |
| first_indexed | 2024-03-09T17:51:42Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:51:42Z |
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| spelling | doaj.art-cae6b8141c874c0cba8774a2a65727e62023-11-24T10:44:41ZengMDPI AGCells2073-44092022-11-011123384110.3390/cells11233841Identification and Validation of <i>RELN</i> Mutation as a Response Indicator for Immune Checkpoint Inhibitor Therapy in Melanoma and Non-Small Cell Lung CancerZhenpeng Li0Xin Wang1Yi Yang2Fuyan Shi3Wenjing Zhang4Qinghua Wang5Suzhen Wang6School of Medical Laboratory, Weifang Medical University, Weifang 261053, ChinaThe Second Affiliated Hospital of Chongqing Medical University, Chongqing 400000, ChinaDepartment of Health Statistics, Key Laboratory of Medicine and Health of Shandong Province, School of Public Health, Weifang Medical University, Weifang 261053, ChinaDepartment of Health Statistics, Key Laboratory of Medicine and Health of Shandong Province, School of Public Health, Weifang Medical University, Weifang 261053, ChinaDepartment of Health Statistics, Key Laboratory of Medicine and Health of Shandong Province, School of Public Health, Weifang Medical University, Weifang 261053, ChinaDepartment of Health Statistics, Key Laboratory of Medicine and Health of Shandong Province, School of Public Health, Weifang Medical University, Weifang 261053, ChinaDepartment of Health Statistics, Key Laboratory of Medicine and Health of Shandong Province, School of Public Health, Weifang Medical University, Weifang 261053, ChinaRemarkable clinical benefits in several advanced cancers are observed under the treatment of immune checkpoint inhibitor (ICI) agents. However, only a smaller proportion of patients respond to the treatments. Reelin (RELN) is frequently mutated in the cancer genome. In this study, the <i>RELN</i> mutation association with ICI treatment efficacy in melanoma and non-small cell lung cancer (NSCLC) was elucidated. Data from 631 melanoma and 109 NSCLC patients with both ICI treatment data and pre-treatment mutational profiles were collected. In addition, from the Cancer Genome Atlas (TCGA) project, we also obtained both tumors to explore the immunologic features behind <i>RELN</i> mutations. Melanoma patients with <i>RELN</i> mutations exhibited a favorable ICI survival benefit when compared with wild-type patients (HR: 0.66, 95% CI: 0.51–0.87, <i>p</i> = 0.003). A higher response rate was also noticed in <i>RELN</i>-mutated patients (38.9% vs. 28.3%, <i>p</i> = 0.017). The association of <i>RELN</i> mutations with a preferable immunotherapy outcome and response was further confirmed in NSCLC. Further exploration demonstrated that favorable immunocyte infiltration and immune response signaling pathways were found in patients with <i>RELN</i> mutations. In this study, <i>RELN</i> mutations were identified to connect with a better immune microenvironment and an improved ICI efficacy in melanoma and NSCLC, which provides a potential biomarker for immunological feature evaluation and immunotherapeutic outcome prediction at the molecular level.https://www.mdpi.com/2073-4409/11/23/3841<i>RELN</i> mutationsimmune checkpoint inhibitormelanomanon-small cell lung cancermolecular determinant |
| spellingShingle | Zhenpeng Li Xin Wang Yi Yang Fuyan Shi Wenjing Zhang Qinghua Wang Suzhen Wang Identification and Validation of <i>RELN</i> Mutation as a Response Indicator for Immune Checkpoint Inhibitor Therapy in Melanoma and Non-Small Cell Lung Cancer Cells <i>RELN</i> mutations immune checkpoint inhibitor melanoma non-small cell lung cancer molecular determinant |
| title | Identification and Validation of <i>RELN</i> Mutation as a Response Indicator for Immune Checkpoint Inhibitor Therapy in Melanoma and Non-Small Cell Lung Cancer |
| title_full | Identification and Validation of <i>RELN</i> Mutation as a Response Indicator for Immune Checkpoint Inhibitor Therapy in Melanoma and Non-Small Cell Lung Cancer |
| title_fullStr | Identification and Validation of <i>RELN</i> Mutation as a Response Indicator for Immune Checkpoint Inhibitor Therapy in Melanoma and Non-Small Cell Lung Cancer |
| title_full_unstemmed | Identification and Validation of <i>RELN</i> Mutation as a Response Indicator for Immune Checkpoint Inhibitor Therapy in Melanoma and Non-Small Cell Lung Cancer |
| title_short | Identification and Validation of <i>RELN</i> Mutation as a Response Indicator for Immune Checkpoint Inhibitor Therapy in Melanoma and Non-Small Cell Lung Cancer |
| title_sort | identification and validation of i reln i mutation as a response indicator for immune checkpoint inhibitor therapy in melanoma and non small cell lung cancer |
| topic | <i>RELN</i> mutations immune checkpoint inhibitor melanoma non-small cell lung cancer molecular determinant |
| url | https://www.mdpi.com/2073-4409/11/23/3841 |
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