Mark J Bailey1, Kristy L Shield-Artin2, Karen Oliva3, Mustafa Ayhan3, Simone Reisman3, Gregory E Rice3
1Zoetis, Veterinary Medicine Research and Development, Parkville, Victoria, Australia.
2Baker IDI Heart and Diabetes Institute, Genomics and Systems Biology, Melbourne, Australia.
3University of Queensland, Centre for Clinical Research, translational Research, Brisbane, Queensland, Australia.
DOI: 10.4103/1477-3163.114216
ABSTRACT
Introduction: Ovarian cancer is the leading cause of death from gynecological cancer. Non-specific symptoms early in disease and the lack of specific biomarkers hinder early diagnosis. Multi-marker blood screening tests have shown promise for improving identification of early stage disease; however, available tests lack sensitivity, and specificity. Materials and Methods: In this study, pooled deeply-depleted plasma from women with Stage 1, 2 or 3 ovarian cancer and healthy controls were used to compare the 2-dimensional gel electrophoresis (2-DE) protein profiles and identify potential novel markers of ovarian cancer progression. Results/Discussion: Stage-specific variation in biomarker expression was observed. For example, apolipoprotein A1 expression is relatively low in control and Stage 1, but shows a substantial increase in Stage 2 and 3, thus, potential of utility for disease confirmation rather than early detection. A better marker for early stage disease was tropomyosin 4 (TPM4). The expression of TPM4 increased by 2-fold in Stage 2 before returning to “normal” levels in Stage 3 disease. Multiple isoforms were also identified for some proteins and in some cases, displayed stage-specific expression. An interesting example was fibrinogen alpha, for which 8 isoforms were identified. Four displayed a moderate increase at Stage 1 and a substantial increase for Stages 2 and 3 while the other 4 showed only moderate increases. Conclusion: Herein is provided an improved summary of blood protein profiles for women with ovarian cancer stratified by stage.
Keywords: Difference in-gel electrophoresis, disease stage, protein depletion, ovarian cancer