In our study, for the short PFS versus long PFS classifica tion, we achieved 82% accuracy with a 6 peptide signa ture. A longer overall survival selleck of the patients classified as long PFS and a shorter overall survival of the patients classified as short PFS was observed. Interestingly, per formance of the signature was improved upon inclusion of Inhibitors,Modulators,Libraries 7 differential time course peptides, the combined 13 peptide ion signature achieving 86% accuracy. In this regard, it has been previously reported that histological response of locally advanced rectal cancer to radiochemo therapy could be predicted by SELDI TOF MS based pro filing and comparison of serum samples collected pre treatment and during treatment. For partial responders versus non partial responders Inhibitors,Modulators,Libraries we achieved 89% accuracy with a 5 peptide signature.
Inclu sion of differential time course peptides did not improve performance of Inhibitors,Modulators,Libraries this signature. Longer duration of progres sion free survival was strongly associated with tumour response as seven out of eleven patients in our study with long PFS also had a partial tumour response upon treat ment, compared to one out of eleven patients in the short PFS group. This suggests that the survival signature is pre dictive of therapy outcome rather than prognostic. As the Kaplan Meier analysis showed, prediction of response using the 5 or 10 peptide signatures was significantly associated with a longer median PFS of those patients, but this did not reach significance for overall survival. In several MALDI serum peptide profiling studies involv ing other solid tumour types by Villanueva et al.
methodologically compara ble to our study, the hypothesis was put forward that can cer type specific changes in exopeptidase activities yield surrogate biomarkers, reflected in the differential abun dance of cleavage products of Inhibitors,Modulators,Libraries common serum substrate proteins. The changes in exopeptidase activity were superimposed on the proteolytic events of the com plement degradation and ex vivo coagulation Inhibitors,Modulators,Libraries pathways and therefore serum specific. Regulated peptides at mz 1690. 925, 1777. 966 and 1865. 002 correspond to those identified in our study at 1690. 90, 1777. 94 and 1864. 95, respectively, previously identified by MALDI TOF TOF based MSMS analysis as Complement C3f. The peptide at 2209. 093 corresponds to the one we detected at 2209. 08, previously identified as HMW Kininogen.
We show that in NSCLC, the identified differential serum peptides changing in abundance over time and those dis tinguishing NSCLC patients from cancer free control sub jects consisted of truncated sequence clusters. The identified peptides were derived from naturally occurring serum peptides and protein precursors, and therefore not likely to be tumor click here derived, thus supporting the exopro tease hypothesis.