Related Experiment Video
Updated: Aug 8, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
SWI/SNF Complex Genomic Alterations as a Predictive Biomarker for Response to Immune Checkpoint Inhibitors in
Di Wang1, Jianchao Wang2, Dongmei Zhou2
1Department of Molecular Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, P.R. China.
Abstract:
Whether there is an association between SWI/SNF genomic alterations in tumors and response to immune checkpoint inhibitors (ICI) remains unclear because prior studies have focused on either an individual gene or a predefined set of genes. Herein, using mutational and clinical data from 832 ICI-treated patients who underwent whole-exome sequencing, including sequencing of all 31 genes of the SWI/SNF complex, we found that SWI/SNF complex alterations were associated with significantly improved overall survival (OS) in melanoma, clear-cell renal cell carcinoma, and gastrointestinal cancer, as well as improved progression-free survival (PFS) in non-small cell lung cancer. Including tumor mutational burden as a variable, the multivariate Cox regression analysis showed SWI/SNF genomic alterations had prognostic value in melanoma [HR, 0.63 (95% confidence interval, CI, 0.47-0.85), P = 0.003], clear-cell renal cell carcinoma [HR, 0.62 (95% CI, 0.46-0.85), P = 0.003], and gastrointestinal cancer [HR, 0.42 (95% CI, 0.18-1.01), P = 0.053]. Furthermore, we used the random forest method for variable screening, identifying 14 genes as a SWI/SNF signature for potential clinical application. Significant correlations were observed between SWI/SNF signature alterations and improved OS and PFS in all cohorts. This suggests that SWI/SNF gene alterations are associated with better clinical outcomes in ICI-treated patients and may serve as a predictive marker for ICI therapy in multiple cancers.
Insights
Genomic alterations in SWI/SNF genes are linked to better outcomes for patients receiving immune checkpoint inhibitors (ICI). This discovery suggests SWI/SNF alterations could predict patient response to ICI therapy across various cancers.
Area of Science:
- Oncology
- Genomics
- Immunotherapy
Background:
- The relationship between SWI/SNF genomic alterations and response to immune checkpoint inhibitors (ICI) is not fully understood.
- Previous research has focused on individual genes or limited gene sets within the SWI/SNF complex.
Purpose of the Study:
- To investigate the association between alterations in all 31 SWI/SNF complex genes and clinical outcomes in patients treated with ICI.
- To identify a potential SWI/SNF gene signature for predicting ICI therapy response.
Main Methods:
- Whole-exome sequencing of SWI/SNF genes in 832 ICI-treated patients.
- Mutational and clinical data analysis, including multivariate Cox regression and random forest methods.
- Prognostic value assessment of SWI/SNF alterations and a derived SWI/SNF signature.
Main Results:
- SWI/SNF complex alterations correlated with improved overall survival (OS) in melanoma, clear-cell renal cell carcinoma, and gastrointestinal cancer.
- Improved progression-free survival (PFS) was observed in non-small cell lung cancer patients with SWI/SNF alterations.
- A 14-gene SWI/SNF signature showed significant correlations with improved OS and PFS across all analyzed cohorts.
Conclusions:
- SWI/SNF gene alterations are associated with favorable clinical outcomes in patients undergoing ICI therapy.
- SWI/SNF alterations may serve as a predictive biomarker for immune checkpoint inhibitor efficacy in multiple cancer types.
- The identified SWI/SNF signature holds potential for clinical application in guiding ICI treatment decisions.
