Using liquid and MALDI-TOF-MS system to filter out protein markers of lung cancer

Objective: To use liquid and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) system to analyze the differentially expressed proteins in the serum of lung cancer patients and control group so as to filter out protein markers of lung cancer. Methods: We randomly divided the serum of the 105 lung cancer patients and 90 control patients (including 44 healthy people and 46 cases of BLDs) into training group (including 60 lung cancer cases and 60 control cases) and validation group [including 45 lung cancer cases (13 patients with early lung cancer and 32 patients with advanced lung cancer) and 30 control cases (both 15 cases of normal and BLDs)]. We analyzed the 195 cases of serum with ClinProt and related software analysis tools - ClinProTools, genetic algorithm (GA) and other biometric methods. Then we smoothed the TIC normally to eliminate chemical and physical electrical noise, analyzed the difference protein between the groups and calculated the differences, and then arrayed the protein according to the degree of the difference in a descending order. GA was used to evaluate the sensitivity and specificity of the difference proteins to establish and validate the discriminable model. Results: Totally 98 difference protein peaks were found when comparing the serum protein of lung cancer patients and control group. The proteins of m/z value 1 865.81 u and 4 054 u had the most difference between the two groups, and the abundance of the two proteins in lung cancer group was higher than that in control group. We established a coordinate system using the protein 1 865.81 u as X -axis and protein 4 054 u as Y-axis (the value represents protein abundance); the few mixed regions showed that the ability of this model to distinguish lung cancer and control group (including normal and BLDs) was good. Using GA, the system gained a diagnosis model with 7 m/z value of 3 192.08, 2 862.55, 4 643.49, 5 336.64, 3 954.88, 9 288.98 u and 4 209.64 u, when using the training group data to construct the model. And when using the validation group to verify, the recognition rate of this model to lung cancer group and control group was 82. 22% (37/45) and 80.00% (24/30) , the recognition rate for early lung cancer was 76. 92% (10/13). Identifying the protein peak of m/z value 1 778, 1 865, 4 209 u, the former two proteins were both C3f, and the third was eukaryotic peptide chain release factor. Conclusion: There are differences among the serum protein expression scores of lung cancer patients, normal persons and BLDs. It is promising to filter out protein markers of lung cancer using ClinProTools, GA and other biometric methods.