Serum Proteomic Profiling of Lung Adenocarcinoma with Brain Metastasis Based on Matrix-Assisted Laser Ionization Time of Flight Mass Spectrometry Analysis

Xinyu Wen¹ and Yaping Tian¹

¹ Department of Clinical Biochemistry, Chinese PLA General Hospital, Beijing 100853, China.

² School of Medicine, Nankai University, Tianjin 300071, China,

³ Department of Radiology, Chinese PLA General Hospital, Beijing 100853, China

*Corresponding author:

Yaping Tian

Department of Clinical Biochemistry

Chinese PLA General Hospital

28th Fuxing Rd, Beijing100853

PR China

Tel:+86-10-6693-9374

Fax:+86-10-8821-7385

E-mail: tianyp61@gmail.com.

Abstract

Background: Once patients presented with brain metastasis, the prognosis is poor with shortened survival of up to 6 months, and therefore early recognition of brain metastasis may be beneficial to outcomes of patients. The present work focused on serum proteomic biomarkers that represent the status of lung adenocarcinoma especially for patients with brain metastasis. Methods: 100 serum samples including 25 from lung adenocarcinoma patients with brain metastasis，25 from lung adenocarcinoma patients without metastasis and 50 from healthy controls were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). ClinProt software and binary logistic regression method were used to develop classification model using MS spectral data. Univariate and Cox multivariate analysis were also performed to evaluate the potential prognostic value of serum peptides. Results: A series of 14 significant short peptides was detected in serum of lung adenocarcinoma patients as compared with healthy controls. Of these, a panel consisting of peptides m/z 1969.9 and 2213.4 Da had the highest diagnostic value for discriminating lung adenocarcinoma from healthy controls with a sensitivity of 91.7% and a specificity of 79.2%. The panel consisting of peptides m/z 1781.5 and 1984.7 Da had the highest diagnostic value for discriminating advanced lung adenocarcinoma with brain metastasis from patients without metastasis with a sensitivity of 84.6% and a specificity of 79.2%. Univariate and Cox multivariate analysis disclosed that peptide m/z 1969.9 Da remained an independent predictors for lung adenocarcinoma patients while peptide m/z 1984.7 Da shows favourable value on pre-warning lung adenocarcinoma patients with brain metastasis after chemotherapy. Conclusion: We have completed a preliminary study to describe the serum proteomic profile of lung adenocarcinoma patients with brain metastasis, and our proteomic models may improve the diagnosis and prognosis of lung adenocarcinoma patients and helps us to better understand the pathogenesis of disease process of brain metastasis.

Keywords: Classification model, prognostic value, serum peptides, lung adenocarcinoma, brain metastasis.

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