SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response
The switch/sucrose non‐fermenting (SWI/SNF) complex family includes important chromatin‐remodeling factors that are frequently mutated in lung adenocarcinoma (LUAD). However, the role of one family member, SMARCA4, in LUAD prognosis and immunotherapy sensitivity remains unclear. In the present study...
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Wiley
2024-12-01
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| Online Access: | https://doi.org/10.1002/2211-5463.13899 |
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| author | Yuming Zhang Dantong Sun Weizhong Han Zhen Yang Yongzhi Lu Xuchen Zhang Yongjie Wang Chuantao Zhang Ning Liu Helei Hou |
| author_facet | Yuming Zhang Dantong Sun Weizhong Han Zhen Yang Yongzhi Lu Xuchen Zhang Yongjie Wang Chuantao Zhang Ning Liu Helei Hou |
| author_sort | Yuming Zhang |
| collection | DOAJ |
| description | The switch/sucrose non‐fermenting (SWI/SNF) complex family includes important chromatin‐remodeling factors that are frequently mutated in lung adenocarcinoma (LUAD). However, the role of one family member, SMARCA4, in LUAD prognosis and immunotherapy sensitivity remains unclear. In the present study, 6745 LUAD samples from the cBioPortal database were used to analyze the relationships between SMARCA4 mutations and patient prognoses and clinical characteristics. Additionally, we examined the correlation between SMARCA4 mutations and prognosis in patients treated with immunotherapy using two immune‐related datasets. SMARCA4 mutations and low expression were associated with shorter survival, and mutations were associated with a high tumor mutational burden and high microsatellite instability. SMARCA4 mutations were accompanied by KRAS, KEAP1, TP53 and STK11 mutations. No significant difference was observed in the immunotherapy response between patients with and without SMARCA4 mutations. When KRAS or STK11 mutations were present, immunotherapy effectiveness was poorer; however, when both SMARCA4 and TP53 mutations were present, immunotherapy was more effective. Furthermore, low SMARCA4 expression predicted a higher immunophenoscore, and SMARCA4 expression was correlated with certain immune microenvironment features. Taken together, our results suggest that SMARCA4 mutations and low expression might be associated with poor LUAD prognosis. Additionally, immunotherapy efficacy in patients with SMARCA4 mutations depended on the co‐mutant genes. Thus, SMARCA4 could be an important factor to be considered for LUAD diagnosis and treatment. |
| format | Article |
| id | doaj-art-200e5a8503d34f1a887319b80bf68395 |
| institution | Kabale University |
| issn | 2211-5463 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-200e5a8503d34f1a887319b80bf683952024-12-02T09:49:10ZengWileyFEBS Open Bio2211-54632024-12-0114122086210310.1002/2211-5463.13899SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy responseYuming Zhang0Dantong Sun1Weizhong Han2Zhen Yang3Yongzhi Lu4Xuchen Zhang5Yongjie Wang6Chuantao Zhang7Ning Liu8Helei Hou9Precision Medicine Center of Oncology The Affiliated Hospital of Qingdao University, Qingdao University ChinaDepartment of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Respiratory Medicine The Affiliated Hospital of Qingdao University ChinaDepartment of Pathology The Affiliated Hospital of Qingdao University, Qingdao University ChinaDepartment of Oncology Qingdao Municipal Hospital ChinaPrecision Medicine Center of Oncology The Affiliated Hospital of Qingdao University, Qingdao University ChinaDepartment of Thoracic Surgery The Affiliation Hospital of Qingdao University ChinaDepartment of Oncology The Affiliated Hospital of Qingdao University ChinaDepartment of Oncology The Affiliated Hospital of Qingdao University ChinaDepartment of Oncology The Affiliated Hospital of Qingdao University ChinaThe switch/sucrose non‐fermenting (SWI/SNF) complex family includes important chromatin‐remodeling factors that are frequently mutated in lung adenocarcinoma (LUAD). However, the role of one family member, SMARCA4, in LUAD prognosis and immunotherapy sensitivity remains unclear. In the present study, 6745 LUAD samples from the cBioPortal database were used to analyze the relationships between SMARCA4 mutations and patient prognoses and clinical characteristics. Additionally, we examined the correlation between SMARCA4 mutations and prognosis in patients treated with immunotherapy using two immune‐related datasets. SMARCA4 mutations and low expression were associated with shorter survival, and mutations were associated with a high tumor mutational burden and high microsatellite instability. SMARCA4 mutations were accompanied by KRAS, KEAP1, TP53 and STK11 mutations. No significant difference was observed in the immunotherapy response between patients with and without SMARCA4 mutations. When KRAS or STK11 mutations were present, immunotherapy effectiveness was poorer; however, when both SMARCA4 and TP53 mutations were present, immunotherapy was more effective. Furthermore, low SMARCA4 expression predicted a higher immunophenoscore, and SMARCA4 expression was correlated with certain immune microenvironment features. Taken together, our results suggest that SMARCA4 mutations and low expression might be associated with poor LUAD prognosis. Additionally, immunotherapy efficacy in patients with SMARCA4 mutations depended on the co‐mutant genes. Thus, SMARCA4 could be an important factor to be considered for LUAD diagnosis and treatment.https://doi.org/10.1002/2211-5463.13899immunotherapy sensitivitylung adenocarcinomaprognosisSMARCA4SWI/SNF complex |
| spellingShingle | Yuming Zhang Dantong Sun Weizhong Han Zhen Yang Yongzhi Lu Xuchen Zhang Yongjie Wang Chuantao Zhang Ning Liu Helei Hou SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response FEBS Open Bio immunotherapy sensitivity lung adenocarcinoma prognosis SMARCA4 SWI/SNF complex |
| title | SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response |
| title_full | SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response |
| title_fullStr | SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response |
| title_full_unstemmed | SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response |
| title_short | SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response |
| title_sort | smarca4 mutations and expression in lung adenocarcinoma prognostic significance and impact on the immunotherapy response |
| topic | immunotherapy sensitivity lung adenocarcinoma prognosis SMARCA4 SWI/SNF complex |
| url | https://doi.org/10.1002/2211-5463.13899 |
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