Proteomic study of benign and malignant pleural effusion

Abstract

Background: Lung adenocarcinoma can easily cause malignant pleural effusion which was difficult to discriminate from benign pleural effusion. Now there was no biomarker with high sensitivity and specificity for the malignant pleural effusion.

Purpose: This study used proteomics technology to acquire and analyze the protein profiles of the benign and malignant pleural effusion, to seek useful protein biomarkers with diagnostic value and to establish the diagnostic model.

Methods: We chose the weak cationic-exchanger magnetic bead (WCX-MB) to purify peptides in the pleural effusion, used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to obtain peptide expression profiles from the benign and malignant pleural effusion samples, established and validated the diagnostic model through a genetic algorithm (GA) and finally identified the most promising protein biomarker.

Results: A GA diagnostic model was established with spectra of 3930.9 and 2942.8 m/z in the training set including 25 malignant pleural effusion and 26 benign pleural effusion samples, yielding both 100 % sensitivity and 100 % specificity. The accuracy of diagnostic prediction was validated in the independent testing set with 58 malignant pleural effusion and 34 benign pleural effusion samples. Blind evaluation was as follows: the sensitivity was 89.6 %, specificity 88.2 %, PPV 92.8 %, NPV 83.3 % and accuracy 89.1 % in the independent testing set. The most promising peptide biomarker was identified successfully: Isoform 1 of caspase recruitment domain-containing protein 9 (CARD9), with 3930.9 m/z, was decreased in the malignant pleural effusion.

Conclusions: This model is suitable to discriminate benign and malignant pleural effusion and CARD9 can be used as a new peptide biomarker.

Keywords: Biomarker; Lung adenocarcinoma; Magnetic bead; Malignant pleural effusion; Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; Proteomic.

Fig. 1

Study flowchart

Fig. 2

Average peptide patterns in malignant pleural effusion (MPE) and benign pleural effusion (BPE)

Fig. 3

ROC curve of 3930.9 and 2942.8 m/z

Fig. 4

Distribution of the samples with the coordinate system established by combining proteins 3930.9 Da (x-axis) and 2942.8 Da (y-axis); the coordinate values represent the relative intensity of the proteins