Abstract 2205: Identification of potential biomarker related to EGFR mutation by functional proteome profiling in primary non-small cell lung cancer

Abstract Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers which the leading cause of cancer-related death worldwide. Recently, epidermal growth factor receptor (EGFR) activating mutations have been proved relevant to NSCLC and let treatment of EGFR tyrosine kinase inhibitors (EGFR-TKIs) become an alternative therapy for NSCLC patients. Despite excellent clinical response to EGFR-TKIs, the intrinsic and acquired resistance to EGFR-TKI created challenges in clinical practice. Although several mechanisms may contribute to solve EGFR-TKIs resistance, there still have 20% to 30% of these patients that how the resistance developed remain unclear. Studies indicated that the increment of membrane efflux may be associated with drug resistance. In this study, we use differential membrane proteomic analysis to identify potential biomarkers for therapeutics of EGFR-TIKs resistance in NSCLC patients.Several primary NSCLC cell lines with different EGFR status were be isolated by our laboratory. Identification of modulators on membrane of primary cancer cells with different EGFR status was analyzed by membrane proteomic assay using LC-MS/ MS. The expression patterns of EGFR mutation cells would compare with that of wild type groups and the potential candidates would be selected by cross the results of interactome profiles of EGFR mutation cell lines. The expression patterns and functional role of these candidates were be examined in NSCLC cells by several molecular, cellular and biochemical analysis; and demonstrated the clinical relevance of these specific targets with EGFR mutation. The expressions of 100 modulators up-regulated in EGFR mutation cells compared with that of wild type group. After cross reacted with the 474 interaction proteins of mutated EGFR, 8 proteins were selected as potential candidates that related to EGFR-TKI resistance, especially the expression of a protein we called SHX in EGFR mutation cells. We demonstrated the real expression levels of SHX in different lung cancer cells, and performed network analysis of SHX and EGFR in translational level.The analysis of differential membrane proteomic found several novelbiomarkers and potential regulation mechanisms that related to the development of EGFR-TKIs resistance in NSCLC. These identification may provide us new direction for exploiting therapeutic strategy for NSCLC treatment in the future. Citation Format: Yuan-Ling Hsu, Szu-Hua Pan. Identification of potential biomarker related to EGFR mutation by functional proteome profiling in primary non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2205. doi:10.1158/1538-7445.AM2017-2205