Non-Small Cell Lung Cancer Biomarkers Discovery Based On Quantitative Proteomic Strategies

Lung cancer-predominantly non-small cell lung cancer (NSCLC)-is the most prevalent cancer in the world, both in terms of incidence and mortality. Clinically, more than80%of NSCLC patients had presented with an advanced stage of disease when therapeutic options were limited. Thus, improvements in early detection strategies and more accurate molecular staging of lung cancer are highly desirable.Among patients with resected NSCLC, prognosis varies widely, even among patients with similar clinicopathological characteristics, demonstrating the need for improved ways to predict treatment outcomesBiomarker is the measurable indicator of specific biological state, especially relevant to risk of presence or stage of specific disease. Proteomic approaches to discover cancer biomarkers for diagnosis, treatment and monitoring may be promising.Mass spectrometry based method becomes the core technology for quantification in proteomic research. Multiplexed quantitative proteomics, may greatly facilitate the process of biomarker discovery for clinical needs.We established a high-quality secretome of A549cells by using the cellular proteome as a reference and to test the merits of this refined secretome for biomarker discovery for non-small cell lung cancer. The serum level of Plasminogen activator Inhibitor1(PAI-1) and C4b-binding Protein (C4BP) in NSCLC blood was verified by enzyme-linked immunosorbent assays (ELISA). Moreover, the serum C4BP level showed a strong association with the clinical staging of NSCLC. Our reference-experiment-driven strategy is simple and widely applicable, and may facilitate the identification of novel promising biomarkers of lung cancer.We screened and quantified prognosis-associated proteins by harnessing current powerful shotgun and targeted proteomic approaches in pre-therapy sera. The blood signatures, such as LRG1(Leucine-rich alpha-2-glycoprotein), SAA(Serum amyloid A protein), C4BP successfully allowed the selection of late stage SCC with a high probability of rapid relapse and may be promising for refining the prognosis of resected SCC in future clinical application.