Prediction of outcome of non-small cell lung cancer patients treated with chemotherapy and bortezomib by time-course MALDI-TOF-MS serum peptide profiling.
BACKGROUND
Only a minority of patients with advanced non-small cell lung cancer (NSCLC) benefit from chemotherapy. Serum peptide profiling of NSCLC patients was performed to investigate patterns associated with treatment outcome.Using magnetic bead-assisted serum peptide capture coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), serum peptide mass profiles of 27 NSCLC patients treated with cisplatin-gemcitabine chemotherapy and bortezomib were obtained. Support vector machine-based algorithms to predict clinical outcome were established based on differential pre-treatment peptide profiles and dynamic changes in peptide abundance during treatment.


RESULTS
A 6-peptide ion signature distinguished with 82% accuracy, sensitivity and specificity patients with a relatively short vs. long progression-free survival (PFS) upon treatment. Prediction of long PFS was associated with longer overall survival. Inclusion of 7 peptide ions showing differential changes in abundance during treatment led to a 13-peptide ion signature with 86% accuracy at 100% sensitivity and 73% specificity. A 5-peptide ion signature could separate patients with a partial response vs. non-responders with 89% accuracy at 100% sensitivity and 83% specificity. Differential peptide profiles were also found when comparing the NSCLC serum profiles to those from cancer-free control subjects.


CONCLUSIONS
This study shows that serum peptidome profiling using MALDI-TOF-MS coupled to pattern diagnostics may aid in prediction of treatment outcome of advanced NSCLC patients treated with chemotherapy.
Voortman
Johannes
J
OncoProteomics Laboratory, Dept Medical Oncology, VUmc-Cancer Center Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.|Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Pham
Thang V
TV
OncoProteomics Laboratory, Dept Medical Oncology, VUmc-Cancer Center Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Knol
Jaco C
JC
OncoProteomics Laboratory, Dept Medical Oncology, VUmc-Cancer Center Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Giaccone
Giuseppe
G
OncoProteomics Laboratory, Dept Medical Oncology, VUmc-Cancer Center Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.|Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Jimenez
Connie R
CR
OncoProteomics Laboratory, Dept Medical Oncology, VUmc-Cancer Center Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.