Of these four peptides, selleck bio two are present in the list Inhibitors,Modulators,Libraries of 47 differential peptides in the healthy versus NSCLC comparison. Ignor ing these two peptides, the signature composed of the remaining 45 peptides yielded the same accuracy, sensitiv ity and specificity as that of the 47 peptide signature. Lit erature supports that serum peptidome patterns that distinguished advanced cases of cancer from cancer free controls were unbiased by gender and age, except for the fact that healthy subjects under 35 years could be distin guished with approximately 70% accuracy. All partic ipating patients in our study were 35 years or older. However, in the cancer free control group, 4 individuals were younger than 35 years and 9 individuals older than 35 years. Comparing these two groups, two peaks met the criteria for differential.
These two peaks did not feature in the classifying signa ture between the NSCLC patients and the cancer free con trols. Peptide identification For structural identification of signature peptides by MS MS, we performed an additional peptide capture on another aliquot of the sera used for profiling. Sera with Inhibitors,Modulators,Libraries highest intensity levels of signature ions were selected for MSMS. For each eluate, a series of four spots was applied to a MALDI target plate, and candidate peaks were sub jected to MSMS in the sample spot associated with the highest intensity for the pertinent peak. Seventeen pep tides were positively identified by MALDI TOFTOF based MSMS analysis, see Table 8 as well as Tables 2, 4 and 6. See Figure 6 for an example of an annotated MSMS spectrum.
In agreement with results by Villanueva et al. in other tumor types, the serum peptide signatures mainly consisted of small sets of overlapping sequences, trun cated in both ends in a ladder like fashion. See Table 8 for truncation ladder examples of Fibrinopeptide Inhibitors,Modulators,Libraries alpha, Complement C3f, Complement C3 beta and Hemoglobin alpha. Discussion In this study, we investigated Inhibitors,Modulators,Libraries the use of serum peptide mass profiling by MALDI TOF MS coupled to bioinfor matics pattern discovery to predict treatment outcome of advanced NSCLC patients treated with platinum based therapy. Additionally, peptide patterns found in NSCLC patients were differential from those found in healthy vol unteers. To our knowledge we are the first to report on a serum peptide signature for response and survival prediction in NSCLC patients treated with cisplatin based chemother apy.
For this study, serum samples were obtained not only pre treatment, but also during treatment and after com pletion of treatment, whereas serum Inhibitors,Modulators,Libraries proteomics studies typically focus on pre treatment samples only. In a study by Taguchi et al. a predictive MALDI TOF MS based pep tide algorithm for good or poor clinical outcome upon epidermal growth factor tyrosine kinase inhibitor therapy was Wortmannin chemical structure established.