The Research On Biomarkers And Its Detection Of Lung Cancer In Exhaled Breath And Exhaled Breath Condesate

Lung cancer is one of the most threatening malignant tumors of human health. Early diagnosis significantly improves the survival rate of patients with lung cancer. Breath detection could be a new, non-invasive and convenient diagnosis method. And the research of biomarkers for lung cancer in the exhale breath provides a key step in the early diagnosis of lung cancer.This paper reports research for lung cancer markers in the detection of volatile organic compounds (VOCs) in exhale breath and exhale breath condensate (EBC) which is as followed.This paper analyzed VOCs in the exhaled breath of 243 samples by solid-phase micro-extraction and gas chromatography-mass spectroscopy technique (SPME-GCMS) system, including 88 samples of lung cancer,70 samples of lung benign disease and 85 samples of health person.26 characteristic VOCs of lung cancer were screened for further statistical approaches to demonstrate the separability between patients group and control group. A diagnostic model for lung cancer was set up based on 7 selected characteristic VOCs. This model achieved a correct rate of 88.5% with a sensitivity of 88.2% (false negative rate of 11.8%) and a specificity of 88.6% (false positive rate of 11.4%).This diagnostic model can be used as a screening method for high-risk groups.The detection of VOCs in lung cancer tissue and lung cancer cell metabolism was conducted using SPME-GCMS system, while chose the normal lung tissue and the primary human bronchial epithelial cell as contrast. As the result it has been found, 2-pentadecanone,nonadecane and eicosane were detected in all the three lung cancer cell lines A549, NCI-H446 and SK-MES-1. By comparing the difference of VOCs in the eighteen lung cancer tissues, it was found out that twelve VOCs such as decane, 2-pentadecanone, nonadecane and eicosane had greater concentration.Meanwhile, the relation between the characteristic VOCs screened from patients with lung cancer and lung cancer cell lines was analyzed. There was certain overlap in the characteristic VOCs (2-pentadecanone), but not exactly the same. This result indicated that tumor cell metabolism is related with characteristic VOCs, but not the only determining factor.This paper makes preliminary research in the detection of lung cancer markers in EBC and chose Carcinoembryonic antigen (CEA) as the biomarker of lung cancer in EBC. A design of the determination of CEA was proposed based on light addressable potentiometric sensor (LAPS), and its performance on the collection of EBCs has been evaluated. The principle of LAPS measurement, along with the test result of hydrogen ion was also analyzed. Urease-CEA antibody was prepared and the process for the detection of CEA using sandwich technic method has been simulated in microloan ELISA plates. Finally a primary experiment has been conducted to demonstrate the feasibility of the detection of CEA in EBC using LAPS.