A47
Can plasma proteomic markers of response to chemotherapy in oesophageal cancer xenografts be applied clinically?
Peter Kelly, Virginia Appleyard, Karen Murray, Fiona Paulin, Alastair Thompson
Dundee University, Dundee, UK
Background
Biomarker discovery for monitoring cancer therapy is made difficult when patient numbers are low and the population is heterogenous in terms of cancer type and treatment modality. The aim of this study was to find proteomic markers of therapeutic response in mice bearing human oesophageal cancer xenografts and validate using clinical samples.
Method
Murine plasma samples were collected from OE19 (adenocarcinoma) and OE21 (squamous cell carcinoma) xenografts after administration of epirubicin, cisplatin, 5-fluorouracil or blank control and analysed by surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectroscopy. Panels of markers were selected using class prediction models that could distinguish between treated and control xenografts. The peaks were identified by mass spectroscopic protein fingerprinting in tryptic digests of purified fractions. Paired samples collected from five oesophageal cancer patients before and after chemotherapy were analysed using the same methodology.
Results
Panels of peaks, shown to differ significantly between treated and untreated xenografts (p<0.05), were found to distinguish between treated and untreated xenografts in the class prediction models with test efficiencies for each cell line and drug combination between 82-100% and nine of these panel members were identified by protein fingerprinting analysis. Of the peaks shown to differ significantly between clinical samples before and after chemotherapy, many of which had similar mass-to-charge ratios to significant peaks identified in the murine samples, three proteins, apolipoprotein A-I, serum amyloid A and transthyretin, were confirmed by protein fingerprint analysis.
Conclusion
This study demonstrates the use of in vivo oesophageal cancer xenografts to enhance biomarker discovery in clinical therapeutics, showing that responses to chemotherapy detected in plasma protein profiles from oesophageal cancer xenografts can also be detected in clinical samples. These markers could potentially be used to monitor response to chemotherapy in oesophageal cancer and should be further assessed within the setting of prospective clinical trials.
