Genomic Mechanisms Underlying the Pathogenesis of Non-Small Cell Lung Cancer (NSCLC) in Young Patients: Translational Research

Abstract

stage I cases for whom ERb immunohistochemistry (IHC) scores were known. ERb was detectable in all cases. Comparing ERb high (Allred score of 4 or more, NZ 20) and ERb low (Allred score of 4 or less, N Z 24) cases, the top PAM50 genes were more informative in ERb high cases (HR 11.7, PZ.0007) compared to ERb low cases (HR 3.38, PZ.045). Similar analyses in the Oncotype DX gene panel did not improve DFS prediction. We next validated the top PAM50 genes in a different cohort of 64 NSCLC cases, which included all stages and histologies and had ERb IHC scores. The top PAM50 genes were also able to predict DFS in this cohort: HR 2.19, PZ.034 in all cases and HR 3.24, PZ.042 in ERb high cases. Pathway analysis indicated that the informative PAM50 genes describe a network that contains the ER, PR, HER2/HER3, neuregulins, FOXC1, FGFR4, and cyclin E. Conclusions: These results suggest that genes involved in interactions between ER, PR and HER signaling may be predictive of NSCLC survival, especially in early-stage lung cancer that is ERb positive, and provide further evidence for the importance of hormonal pathways in the biology of lung cancer. Author Disclosure: J.M. Siegfried: E. Research Grant; NIH, V Foundation, Somalogic, Inc. K. Advisory Board; Free to Breathe. Y. Lin: E. Research Grant; NIH. S. Dacic: E. Research Grant; NIH. L.P. Stabile: E. Research Grant; NIH. B. Diergaarde: E. Research Grant; NIH. H. Lin: None. T. Nukui: None. M. Romkes: E. Research Grant; NIH.