Identification of Serum Peptidome Signatures of Non-Small Cell Lung Cancer

Abstract

Due to high mortality rates of lung cancer, there is a need for identification of new, clinically useful markers, which improve detection of this tumor in early stage of disease. In the current study, serum peptide profiling was evaluated as a diagnostic tool for non-small cell lung cancer patients. The combination of the ZipTip technology with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for the analysis of peptide pattern of cancer patients (n = 153) and control subjects (n = 63) was presented for the first time. Based on the observed significant differences between cancer patients and control subjects, the classification model was created, which allowed for accurate group discrimination. The model turned out to be robust enough to discriminate a new validation set of samples with satisfactory sensitivity and specificity. Two peptides from the diagnostic pattern for non-small cell lung cancer (NSCLC) were identified as fragments of C3 and fibrinogen α chain. Since ELISA test did not confirm significant differences in the expression of complement component C3, further study will involve a quantitative approach to prove clinical utility of the other proteins from the proposed multi-peptide cancer signature.

Keywords: MALDI-TOF-MS; ZipTip enrichment; non-small cell lung cancer; peptide profiling.

Figure 1

(A) Mass spectrum of m/z 1520.8456 with assigned oxidative modification of m/z signal 1504.853; (B) Mass spectrum of m/z 1545.6249 represent with assigned phosphorylation modification of m/z signal 1465.657.