MALDI-ToF mass spectrometry for the rapid diagnosis of cancerous lung nodules.

Abstract

Recently, tissue-based methods for proteomic analysis have been used in clinical research and appear reliable for digestive, brain, lymphomatous, and lung cancers classification. However simple, tissue-based methods that couple signal analysis to tissue imaging are time consuming. To assess the reliability of a method involving rapid tissue preparation and analysis to discriminate cancerous from non-cancerous tissues, we tested 141 lung cancer/non-tumor pairs and 8 unique lung cancer samples among the stored frozen samples of 138 patients operated on during 2012. Samples were crushed in water, and 1.5 µl was spotted onto a steel target for analysis with the Microflex LT analyzer (Bruker Daltonics). Spectra were analyzed using ClinProTools software. A set of samples was used to generate a random classification model on the basis of a list of discriminant peaks sorted with the k-nearest neighbor genetic algorithm. The rest of the samples (n = 43 cancerous and n = 41 non-tumoral) was used to verify the classification capability and calculate the diagnostic performance indices relative to the histological diagnosis. The analysis found 53 m/z valid peaks, 40 of which were significantly different between cancerous and non-tumoral samples. The selected genetic algorithm model identified 20 potential peaks from the training set and had 98.81% recognition capability and 89.17% positive predictive value. In the blinded set, this method accurately discriminated the two classes with a sensitivity of 86.7% and a specificity of 95.1% for the cancer tissues and a sensitivity of 87.8% and a specificity of 95.3% for the non-tumor tissues. The second model generated to discriminate primary lung cancer from metastases was of lower quality. The reliability of MALDI-ToF analysis coupled with a very simple lung preparation procedure appears promising and should be tested in the operating room on fresh samples coupled with the pathological examination.