Gene expression profiles in peripheral blood as a biomarker in cancer patients receiving peptide vaccination

BACKGROUND: Because only a subset of patients show clinical responses to peptide-based cancer vaccination, it is critical to identify biomarkers for selecting patients who would most likely benefit from this treatment. METHODS: The authors characterized the gene expression profiles in peripheral blood of vaccinated patients to identify biomarkers to predict patient prognosis. Peripheral blood was obtained from advanced castration-resistant prostate cancer patients, who survived for >900 days (long-term survivors, n = 20) or died within 300 days (short-term survivors, n = 20) after treatment with personalized peptide vaccination. Gene expression profiles in prevaccination and postvaccination peripheral blood mononuclear cells (PBMCs) were assessed by DNA microarray. RESULTS: There were no statistically significant differences in the clinical or pathological features between the 2 groups. Microarray analysis of prevaccination PBMCs identified 19 genes that were differentially expressed between the short-term and long-term survivors. Among the 15 up-regulated genes in the short-term survivors, 13 genes, which were also differentially expressed in postvaccination PBMCs, were associated with gene signatures of granulocytes. When a set of 4 differentially expressed genes were selected as the best combination to determine patient survival, prognosis was correctly predicted in 12 of 13 patients in a validation set (accuracy, 92%). CONCLUSIONS: These results suggested that abnormal granulocytes present in the PBMC faction may contribute to poor prognosis in advanced prostate cancer patients receiving personalized peptide vaccination. Gene expression profiling in peripheral blood might thus be informative for devising better therapeutic strategies by predicting patient prognosis after cancer vaccines. Cancer 2012;118: 320821. (C) 2011 American Cancer Society.