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Data from SMARCA4/BRG1 Is a Novel Prognostic Biomarker Predictive of Cisplatin-Based Chemotherapy Outcomes in Resected Non–Small Cell Lung Cancer
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Data from SMARCA4/BRG1 Is a Novel Prognostic Biomarker Predictive of Cisplatin-Based Chemotherapy Outcomes in Resected Non–Small Cell Lung Cancer
Data from SMARCA4/BRG1 Is a Novel Prognostic Biomarker Predictive of Cisplatin-Based Chemotherapy Outcomes in Resected Non–Small Cell Lung Cancer
EB
Erica Hlavin Bell
Erica Hlavin Bell
AC
Arup R. Chakraborty
Arup R. Chakraborty
XM
Xiaokui Mo
Xiaokui Mo
ZL
Ziyan Liu
Ziyan Liu
KS
Konstantin Shilo
Konstantin Shilo
SK
Simon Kirste
Simon Kirste
PS
Petra Stegmaier
Petra Stegmaier
MM
Maureen McNulty
Maureen McNulty
NK
Niki Karachaliou
Niki Karachaliou
RR
Rafael Rosell
Rafael Rosell
GB
Gerold Bepler
Gerold Bepler
DC
David P. Carbone
David P. Carbone
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31 March 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/1078-0432.c.6524268
Abstract
Purpose: Identification of predictive biomarkers is critically needed to improve selection of patients who derive the most benefit from platinum-based chemotherapy. We hypothesized that decreased expression of SMARCA4/BRG1, a known regulator of transcription and DNA repair, is a novel predictive biomarker of increased sensitivity to adjuvant platinum-based therapies in non–small cell lung cancer (NSCLC).Experimental Design: The prognostic value was tested using a gene-expression microarray from the Director's Challenge Lung Study (n = 440). The predictive significance of SMARCA4 was determined using a gene-expression microarray (n = 133) from control and treatment arms of the JBR.10 trial of adjuvant cisplatin/vinorelbine. Kaplan–Meier method and log-rank tests were used to estimate and test the differences of probabilities in overall survival (OS) and disease-specific survival (DSS) between expression groups and treatment arms. Multivariate Cox regression models were used while adjusting for other clinical covariates.Results: In the Director's Challenge Study, reduced expression of SMARCA4 was associated with poor OS compared with high and intermediate expression (P < 0.001 and P = 0.009, respectively). In multivariate analysis, compared with low, high SMARCA4 expression predicted a decrease in risk of death [HR, 0.6; 95% confidence interval (CI), 0.4–0.8; P = 0.002]. In the JBR.10 trial, improved 5-year DSS was noted only in patients with low SMARCA4 expression when treated with adjuvant cisplatin/vinorelbine [HR, 0.1; 95% CI, 0.0–0.5, P = 0.002 (low); HR, 1.0; 95% CI, 0.5–2.3, P = 0.92 (high)]. An interaction test was highly significant (P = 0.01).Conclusions: Low expression of SMARCA4/BRG1 is significantly associated with worse prognosis; however, it is a novel significant predictive biomarker for increased sensitivity to platinum-based chemotherapy in NSCLC. Clin Cancer Res; 22(10); 2396–404. ©2015 AACR.
Keywords
GENE EXPRESSION
EXPRESSION OF SMARCA4/BRG1
MULTIVARIATE ANALYSIS
PREDICTIVE SIGNIFICANCE
ADJUVANT CISPLATIN/VINORELBINE
JBR.10 TRIAL
BIOMARKER OF INCREASED
PLATINUM BASED CHEMOTHERAPY
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