Poster Presentation 6th Australian Health and Medical Research Congress 2012

Identification of biomarkers of chemoradiotherapy-induced toxicity in upper gastrointestinal cancers (#315)

Imogen A White 1 , Joanne M Bowen 2 , Kerry Kristaly 1 , Lorelle Smith 3 , Sarah K Thompson 3 , Damian J Hussey 4 , Tanya Irvine 4 , David I Watson 4 , Dorothy MK Keefe 1
  1. Discipline of Medicine, University of Adelaide, Adelaide, Australia
  2. Discipline of Physiology, University of Adelaide, Adelaide, Australia
  3. Discipline of Surgery, Royal Adelaide Hospital, Adelaide, Australia
  4. Department of Surgery, Flinders Medical Centre, Adelaide, Australia

Inflammation of the mucous membranes of the body in response to cancer chemotherapy and radiotherapy is referred to as mucositis and is a major clinical problem in oncology. Mucositis can result in pain and ulceration in the oral cavity and gastrointestinal (GI) tract, bloating, vomiting and diarrhoea. Mucositis occurs in approximately 40% of patients receiving standard doses of cancer treatment and no clinical tool exists to predict which patients are most at risk of severe symptoms. Patients who suffer from severe mucositis during their treatment course will have specific gene expression profiles prior to therapy, which can be measured by genome analysis. The aim of this study was to identify immune response genes in upper GI cancer patients as markers of chemoradiotherapy (CRT)-induced mucositis. Bloods were collected prior to CRT. RNA was extracted from whole blood and innate and adaptive immune response genes were profiled by RT-PCR. Blood samples were collected from patients diagnosed with oesophageal adenocarcinoma (N=9), oesophageal squamous cell carcinoma (N=4), gastro/oesophageal junction adenocarcinoma (N=4) and gastric adenocarcinoma (N=7). GI toxicities included oral mucositis, encompassing mouth and throat ulcers and soreness (15 [62.5%]), nausea and vomiting (14 [58.3%]), diarrhoea (7 [29.2%]) and others such as xerostomia, dysgeusia, oral thrush, reflux and constipation (7 [29.2%]). The highest RNA concentrations were achieved by incubating whole blood for 20 to 24 h prior to extraction. RIN scores were between 7.4 and 8.8. Gene expression profiles will be compared between patients who experienced severe mucositis vs. no/minor mucositis. It is hypothesised that baseline expression of key mediators of inflammatory tissue damage, including pro-inflammatory cytokines and transcription factors, will be measurably different in patients who do or do not develop severe mucosal damage. Variances in gene expression will highlight target biomarkers, useful in mucositis prediction.