Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

MALDI imaging identifies transketolase to be up-regulated in serous ovarian cancer patients following chemotherapy-resistant disease relapse (#755)

Tannith M Noye 1 , Parul Mittal 2 , Noor A Lokman 1 , Oliver Schilling 3 , Peter Hoffmann 4 , Martin K Oehler 1 5 , Carmela Ricciardelli 1
  1. Adelaide Medical School, Obstetrics and Gynaecology, University of Adelaide, Adelaide, South Australia, Australia
  2. Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia
  3. Institute for Clinical Pathology, Albert-Ludwigs Universtität, Freiburg, Baden-Württemberg, Germany
  4. Future Industries Institute, University of South Australia, Adelaide, South Australia, Australia
  5. Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia

Ovarian cancer is the most lethal gynaecological disease, with poor 5-year survival rates and limited treatment options for patients who develop resistant disease. The majority of ovarian malignancies, up to 70% of cases, are high-grade serous carcinomas that have high chemosensitivity to first line platinum-based therapies. However, 75% of patients will become chemoresistant, following relapse.  The underlying mechanism for developing resistance to chemotherapy in ovarian cancer is poorly understood. In this study, we employed peptide matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in formalin fixed paraffin embedded sections of ovarian cancer tissues at the time of diagnosis and following relapse from 4 patients with serous cancer. Using, MALDI-MSI we have identified m/z features that were present in relapsed tissues but absent in ovarian cancer tissues at diagnosis. One of these was identified as transketolase using LC-MS/MS and data dependent analysis on paraffin sections. Transketolase was validated by immunohistochemistry and was elevated by ~3 fold in relapse tissues compared to matching ovarian cancer tissues at diagnosis (P=0.035, paired t-test). In addition, transketolase (TKT) expression was significantly increased (P=0.0075, unpaired t-test) in carboplatin resistant CAOV3 cells compared to parental cells measured by qRT-PCR. In summary, MALDI-MSI has the potential to identify proteins associated with chemotherapy resistance that can be evaluated as a novel therapeutic target.