Abstract 4124: Pre-treatment complement system serum protein levels predict pathological response to neoadjuvant chemoradiotherapy for esophageal cancer

Abstract

Abstract Introduction: Esophageal cancer has one of the worst prognosis of all cancers, and its incidence is increasing rapidly in the Western world. The standard of care for patients with esophageal cancer involves neoadjuvant chemoradiotherapy (neo-CRT) followed by surgery. Unfortunately, only ∼30% of esophageal cancer patients respond to neo-CRT. The aim of this study was to analyse the serum proteome early into neo-CRT to reveal biomarkers indicative of response to therapy. Methods: 31 esophageal cancer patients received a standard neo-CRT regimen. Pathological response to therapy was assessed using the Mandard Tumour Regression Grade system. Serum was collected at pre-treatment, 24 h and 48 h timepoints into treatment. Albumin/IgG-depleted serum samples were analyzed using SELDI-TOF-MS. Protein/peptide expression difference mapping was performed and the data applied to the EPO-KB database. Subsequently, high-scoring candidates were assayed by ELISA. A leave-one-out cross validation (LOOCV) predictive algorithm was employed to assess the ability of candidate biomarkers to correctly predict therapeutic outcome. Results: 16 patients had a poor response to therapy, while 15 had a good response. On CM10 chips, 9 protein peaks were significantly different between the two treatment response groups, some at baseline, others at 24 h and 48 h into neo-CRT. SELDI spectral peaks m/z_8617.685 and m/z_8928.422 were identified as the complement proteins C4a and C3a, respectively, via the EPO-KB. ELISA revealed significantly higher pre-treatment levels of C4a and C3a in serum from poor versus good responders. Subdivision of the response groups by TRG indicated an inverse correlation between levels of C4a and C3a and pathological response to neo-CRT. In a pre-treatment setting, LOOCV analysis revealed that these two serum proteins could predict patient response to neo-CRT with a sensitivity and specificity of 78.6% and 83.3%, respectively. Conclusion: In a relatively non-invasive approach, this study has identified that pre-treatment levels of serum C4a and C3a are potential pre-treatment biomarkers predicting response to neo-CRT for esophageal cancer. Additional serum proteins are being validated to further improve the sensitivity and specificity of predicting esophageal patient response to treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4124. doi:10.1158/1538-7445.AM2011-4124