TY - JOUR
T1 - Prediction of survival in resected non-small cell lung cancer using a protein expression-based risk model
T2 - Implications for personalized chemoprevention and therapy
AU - Gold, Kathryn A.
AU - Kim, Edward S.
AU - Liu, Diane D.
AU - Yuan, Ping
AU - Behrens, Carmen
AU - Solis, Luisa M.
AU - Kadara, Humam
AU - Rice, David C.
AU - Wistuba, Ignacio I.
AU - Swisher, Stephen G.
AU - Hofstetter, Wayne L.
AU - Lee, J. Jack
AU - Hong, Waun K.
PY - 2014/4/1
Y1 - 2014/4/1
N2 - Purpose: Patients with resected non-small cell lung cancer (NSCLC) are at risk for recurrence of disease, but we do not have tools to predict which patients are at highest risk. We set out to create a risk model incorporating both clinical data and biomarkers. Experimental Design: Weassembled a comprehensive database with archival tissues and clinical followup from patients with NSCLC resected between 2002 and 2005. Twenty-one proteins identified from our preclinical studies as related to lung carcinogenesis were investigated, including pathways related to metabolism, DNA repair, inflammation, and growth factors. Expression of proteins was quantified using immunohistochemistry. Immunohistochemistry was chosen because it is widely available and can be performed on formalin-fixed paraffin-embedded specimens. Cox models were fitted to estimate effects of clinical factors and biomarkers on recurrence-free survival (RFS) and overall survival (OS). Results: A total of 370 patients are included in our analysis. With median follow-up of 5.3 years, median OS is 6.4 years. A total of 209 cases with recurrence or death were observed. Multicovariate risk models for RFS and OS were developed including relevant biomarkers, age, and stage. Increased expression of phosphoadenosine monophosphate-activated protein kinase (pAMPK), phospho-mTOR (pmTOR), epithelial cell adhesion molecule (EpCAM), and calcium/calmodulin-dependent serine protein kinase were significant (P < 0.05) predictors for favorable RFS; insulin receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and insulin-like growth factor-1 receptor predicted for unfavorable RFS. Significant (P < 0.05) predictors for favorable OS include pAMPK, pmTOR, and EpCAM; CXCR2 and flap structure-specific endonuclease-1 predicted unfavorable OS. Conclusion: We have developed a comprehensive risk model predictive for recurrence in our large retrospective database, which is one of the largest reported series of resected NSCLC.
AB - Purpose: Patients with resected non-small cell lung cancer (NSCLC) are at risk for recurrence of disease, but we do not have tools to predict which patients are at highest risk. We set out to create a risk model incorporating both clinical data and biomarkers. Experimental Design: Weassembled a comprehensive database with archival tissues and clinical followup from patients with NSCLC resected between 2002 and 2005. Twenty-one proteins identified from our preclinical studies as related to lung carcinogenesis were investigated, including pathways related to metabolism, DNA repair, inflammation, and growth factors. Expression of proteins was quantified using immunohistochemistry. Immunohistochemistry was chosen because it is widely available and can be performed on formalin-fixed paraffin-embedded specimens. Cox models were fitted to estimate effects of clinical factors and biomarkers on recurrence-free survival (RFS) and overall survival (OS). Results: A total of 370 patients are included in our analysis. With median follow-up of 5.3 years, median OS is 6.4 years. A total of 209 cases with recurrence or death were observed. Multicovariate risk models for RFS and OS were developed including relevant biomarkers, age, and stage. Increased expression of phosphoadenosine monophosphate-activated protein kinase (pAMPK), phospho-mTOR (pmTOR), epithelial cell adhesion molecule (EpCAM), and calcium/calmodulin-dependent serine protein kinase were significant (P < 0.05) predictors for favorable RFS; insulin receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and insulin-like growth factor-1 receptor predicted for unfavorable RFS. Significant (P < 0.05) predictors for favorable OS include pAMPK, pmTOR, and EpCAM; CXCR2 and flap structure-specific endonuclease-1 predicted unfavorable OS. Conclusion: We have developed a comprehensive risk model predictive for recurrence in our large retrospective database, which is one of the largest reported series of resected NSCLC.
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U2 - 10.1158/1078-0432.CCR-13-1959
DO - 10.1158/1078-0432.CCR-13-1959
M3 - Article
C2 - 24366692
AN - SCOPUS:84898735133
SN - 1078-0432
VL - 20
SP - 1946
EP - 1954
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -