期刊
MOLECULAR ONCOLOGY
卷 15, 期 2, 页码 462-472出版社
WILEY
DOI: 10.1002/1878-0261.12831
关键词
immunotherapy; KRAS; lung adenocarcinoma; nonimmunotherapy; prognostics biomarker; SMARCA4 mutation
类别
资金
- National Cancer Institute's Cancer Center Support Grant [P30CA012197, R21CA253362]
- Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)-Center for Integrative Medicine
- Cancer Genetics and Metabolism Program PUSH Pilot Award from Comprehensive Cancer Center at Wake Forest Baptist Medical Center
- Hanes and Willis Professorship in Cancer
- Charles L. Spurr Professorship Fund
- National Foundation for Cancer Research
This study revealed that mutations of SMARCA4 serve as a genetic factor leading to adverse clinical outcomes in lung adenocarcinoma, regardless of whether patients were treated with nonimmunotherapy or immunotherapy.
KRAS is a key oncogenic driver in lung adenocarcinoma (LUAD). Chromatin-remodeling gene SMARCA4 is comutated with KRAS in LUAD; however, the impact of SMARCA4 mutations on clinical outcome has not been adequately established. This study sought to shed light on the clinical significance of SMARCA4 mutations in LUAD. The association of SMARCA4 mutations with survival outcomes was interrogated in four independent cohorts totaling 564 patients: KRAS-mutant patients with LUAD who received nonimmunotherapy treatment from (a) The Cancer Genome Atlas (TCGA) and (b) the MSK-IMPACT Clinical Sequencing (MSK-CT) cohorts; and KRAS-mutant patients with LUAD who received immune checkpoint inhibitor-based immunotherapy treatment from (c) the MSK-IMPACT (MSK-IO) and (d) the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) immunotherapy cohorts. Of the patients receiving nonimmunotherapy treatment, in the TCGA cohort (n = 155), KRAS-mutant patients harboring SMARCA4 mutations (KS) showed poorer clinical outcome [P = 6e-04 for disease-free survival (DFS) and 0.031 for overall survival (OS), respectively], compared to KRAS-TP53 comutant (KP) and KRAS-only mutant (K) patients; in the MSK-CT cohort (n = 314), KS patients also exhibited shorter OS than KP (P = 0.03) or K (P = 0.022) patients. Of patients receiving immunotherapy, KS patients consistently exhibited the shortest progression-free survival (PFS; P = 0.0091) in the MSK-IO (n = 77), and the shortest PFS (P = 0.0026) and OS (P = 0.0014) in the WFBCCC (n = 18) cohorts, respectively. Therefore, mutations of SMARCA4 represent a genetic factor leading to adverse clinical outcome in lung adenocarcinoma treated by either nonimmunotherapy or immunotherapy.
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