TY - JOUR
T1 - Prediction of postoperative recurrence-free survival in non-small cell lung cancer by using an internationally validated gene expression model
AU - Mitra, Ranjana
AU - Lee, Jinseon
AU - Jo, Jisuk
AU - Milani, Monica
AU - McClintick, Jeanette N.
AU - Edenberg, Howard J.
AU - Kesler, Kenneth A.
AU - Rieger, Karen M.
AU - Badve, Sunil
AU - Cummings, Oscar W.
AU - Mohiuddin, Ahmed
AU - Thomas, Dafydd G.
AU - Luo, Xianghua
AU - Juliar, Beth E.
AU - Li, Lang
AU - Mesaros, Clementina
AU - Blair, Ian A.
AU - Srirangam, Anjaiah
AU - Kratzke, Robert A.
AU - McDonald, Clement J.
AU - Kim, Jhingook
AU - Potter, David A.
PY - 2011/5/1
Y1 - 2011/5/1
N2 - Purpose: This study was performed to discover prognostic genomic markers associated with postoperative outcome of stage I to III non-small cell lung cancer (NSCLC) that are reproducible between geographically distant and demographically distinct patient populations. Experimental Design: American patients (n = 27) were stratified on the basis of recurrence and microarray profiling of their tumors was performed to derive a training set of 44 genes. A larger Korean patient validation cohort (n = 138) was also stratified by recurrence and screened for these genes. Four reproducible genes were identified and used to construct genomic and clinicogenomic Cox models for both cohorts. Results: Four genomic markers, DBN1 (drebrin 1), CACNB3 (calcium channel beta 3), FLAD1 (PP591; flavin adenine dinucleotide synthetase), and CCND2 (cyclin D2), exhibited highly significant differential expression in recurrent tumors in the training set (P < 0.001). In the validation set, DBN1, FLAD1 (PP591), and CACNB3 were significant by Cox univariate analysis (P ≤ 0.035), whereas only DBN1 was significant by multivariate analysis. Genomic and clinicogenomic models for recurrence-free survival (RFS) were equally effective for risk stratification of stage I to II or I to III patients (all models P < 0.0001). For stage I to II or I to III patients, 5-year RFS of the low- and high-risk patients was approximately 70% versus 30% for both models. The genomic model for overall survival of stage I to III patients was improved by addition of pT and pN stage (P < 0.0013 vs. 0.010). Conclusion: A 4-gene prognostic model incorporating the multivariate marker DBN1 exhibits potential clinical utility for risk stratification of stage I to III NSCLC patients.
AB - Purpose: This study was performed to discover prognostic genomic markers associated with postoperative outcome of stage I to III non-small cell lung cancer (NSCLC) that are reproducible between geographically distant and demographically distinct patient populations. Experimental Design: American patients (n = 27) were stratified on the basis of recurrence and microarray profiling of their tumors was performed to derive a training set of 44 genes. A larger Korean patient validation cohort (n = 138) was also stratified by recurrence and screened for these genes. Four reproducible genes were identified and used to construct genomic and clinicogenomic Cox models for both cohorts. Results: Four genomic markers, DBN1 (drebrin 1), CACNB3 (calcium channel beta 3), FLAD1 (PP591; flavin adenine dinucleotide synthetase), and CCND2 (cyclin D2), exhibited highly significant differential expression in recurrent tumors in the training set (P < 0.001). In the validation set, DBN1, FLAD1 (PP591), and CACNB3 were significant by Cox univariate analysis (P ≤ 0.035), whereas only DBN1 was significant by multivariate analysis. Genomic and clinicogenomic models for recurrence-free survival (RFS) were equally effective for risk stratification of stage I to II or I to III patients (all models P < 0.0001). For stage I to II or I to III patients, 5-year RFS of the low- and high-risk patients was approximately 70% versus 30% for both models. The genomic model for overall survival of stage I to III patients was improved by addition of pT and pN stage (P < 0.0013 vs. 0.010). Conclusion: A 4-gene prognostic model incorporating the multivariate marker DBN1 exhibits potential clinical utility for risk stratification of stage I to III NSCLC patients.
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U2 - 10.1158/1078-0432.CCR-10-1803
DO - 10.1158/1078-0432.CCR-10-1803
M3 - Article
C2 - 21242119
AN - SCOPUS:79955487252
SN - 1078-0432
VL - 17
SP - 2934
EP - 2946
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 9
ER -