Mass spectrometry-based serum peptidome profiling accurately and reliably predicts outcomes of pemetrexed plus platinum chemotherapy in patients with advanced lung adenocarcinoma

Abstract

BackgroundAlthough pemetrexed plus cis/carboplatin has become the most effective chemotherapy regimen for patients with advanced lung adenocarcinoma, predictive biomarkers are not yet available, and new tools to identify chemosensitive patients who would likely benefit from this treatment are desperately needed. In this study, we constructed and validated predictive peptide models using the serum peptidome profiles of two datasets.MethodsOne hundred eighty-three patients treated with first-line platinum-based pemetrexed treatment for advanced lung adenocarcinoma were retrospectively enrolled and randomized into the training (n = 92) or validation (n = 91) set, and pre-treatment serum samples were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and ClinProTools software. Serum peptidome profiles from the training set were used to identify potential predictive peptide biomarkers and construct a predictive peptide model for accurate group discrimination; which was then used to classify validation samples into “good” and “poor” outcome groups. The clinical outcomes of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were analyzed based on the classification result.ResultsEight potential peptide biomarkers were identified. A predictive peptide model based on four distinct m/z features (2,142.12, 3,316.19, 4,281.94, and 6,624.02 Da) was developed based on the clinical outcomes of training set patients after first-line pemetrexed plus platinum treatment. In the validation set, the good group had significantly higher ORR (49.1% vs. 8.3%, P <0.001) and DCR (96.4% vs. 47.2%, P <0.001), and longer PFS (7.3 months vs. 2.7 months, P <0.001) vs. the poor group. However, the model did not predict OS (13.6 months vs. 12.7 months, P = 0.0675).ConclusionOur predictive peptide model could predict pemetrexed plus platinum treatment outcomes in patients with advanced lung adenocarcinoma and might thus facilitate appropriate patient selection. Further studies are needed to confirm these findings.

The Relevance of Mass Spectrometry Analysis for Personalized Medicine through Its Successful Application in Cancer “Omics”

“…In another experiment; Wang et al used MB-WCX coupled with MALDI-TOF MS to compare the serum peptidome profiles of advanced lung adenocarcinoma patients treated using first-line platinum-based pemetrexed chemotherapy [114]. Using the MS-based technique and ClinProTools software; these profiles were used to determine potential predictive peptide biomarkers and develop a predictive peptide model for accurate group discrimination.…”

“…Thus; the predictive peptide model based on four distinct m / z characteristics was determined by the clinical outcomes of patients on first line pemetrexed plus platinum treatment. Lastly; eight potential peptide biomarkers were identified based on eight mass [Da] peaks significantly differentially expressed in the patient training set; of these; only two were the peptide sequences and proteins were known; uridylate kinase and Glucosamine--fructose-6-phosphate aminotransferase [114].…”

Identification of serum biomarkers to predict pemetrexed/platinum chemotherapy efficacy for advanced lung adenocarcinoma patients by data-independent acquisition (DIA) mass spectrometry analysis with parallel reaction monitoring (PRM) verification

“…Mass spectrometry techniques are widely used in the investigation of biomarkers. Using matrix-assisted laser desorption ionization timeof-flight mass spectrometry (MALDI-TOF-MS)-based serum peptidome profiling, Wang et al discovered 8 potential peptide biomarkers that can predict outcomes of pemetrexed plus platinum regimens for advanced lung adenocarcinoma patients (12). Furthermore, Tian et al developed a 7-metabolite panel that was predictive of pemetrexed plus platinum doublet in NSCLC patients by serum metabolite profiling analysis (13).…”