Response and toxicity prediction by MALDI-TOF-MS serum peptide profiling in patients with non-small cell lung cancer

We validated a previously reported proteomic signature, associated with treatment outcome, in an independent cohort of patients with non-small cell lung cancer (NSCLC). A novel peptide signature was developed to predict toxicity.

Using automated magnetic C18 bead-assisted serum peptide capture coupled to MALDI-TOF MS, we conducted serum peptide profiling of 50 NCSLC patients participating in a phase II trial of erlotinib and sorafenib. On the obtained peptide mass profiles, we applied a previously described proteomic classification algorithm. Additionally, associations between observed side effects and peptide profiles were investigated.

Application of the previously acquired algorithm successfully classified the new cohort of patients in groups significantly associated with the outcome. The "poor" group exhibited shorter median progression-free survival (PFS) and overall survival (OS) of 1.35 and 1.98 months (with p = 0.00677 and p = 0.00002, respectively) while the "good" group had significantly longer PFS and OS (10.63 and 14.4 months with p = 0.00142 and p = 0.00002, respectively), compared to average OS and PFS. Two specific peptides were detected in the sera of all patients that developed severe toxicity.

Our results provide an algorithm that, following prospective validation in larger cohorts, could assist treatment selection of patients with NSCLC in the first line setting.