Investigating Synovial Sarcoma, X breakpoint proteins in ovarian cancer

Grayson, Kelly

Abstract

Ovarian cancer (OC) affects around 7500 women in the UK every year, but despite this, there is no effective screening strategy or standard treatment. There is a strong correlation between OC prognosis and the stage of diagnosis. If diagnosed during stage I, OC has over a 90% 5-year survival rate, however vague symptoms often lead to late stage diagnosis and a correspondingly poor survival rate. CA-125 is the ‘gold standard’ clinically used serum biomarker for confirming and monitoring OC in patients but is not always present in early stage disease. Previous research has identified expression of the cancer testis antigen SSX2 in stage I and II OC at significantly higher levels than CA- 125.
The primary objective of this study was to evaluate patient tumour samples for SSX2 expression alongside other SSX variants, SSX3 and SSX4, to expand investigation into SSX family members as biomarkers for OC. Levels of SSX variants were evaluated for correlations against OC subtype as well as disease stage to acknowledge the diverse histotypes of OC. SSX2 and SSX3 expression was shown to be increased in early stage OC when compared to normal adjacent tissue. Metastatic OC was also found to significantly express SSX2, suggesting that SSX3 may be a superior early stage biomarker candidate. Collectively this data revealed variations in the level of SSX expression across OC stages and histotypes.
Following successful development of in vitro overexpression models of SSX family members, global transcriptomic profiling was used to identify novel transcripts and pathways altered by SSX2A, SSX2B and SSX3. Transcriptional profiling of each overexpression model highlighted that SSX variants modulate unique and common downstream targets and resulting functions. This work suggested that SSX2A, SSX2B and SSX3, alone or in combination, appear to contribute to cancer progression and clinical outcomes.
Consequently, in vitro and in vivo studies were performed to assess the impact of each SSX family member on cell proliferation and motility in OC. All SSX variants in this study, SSX2A, SSX2B, SSX3 and SSX4 significantly promoted cell proliferation in an OC cell line. Changes were also seen in key epithelial to mesenchymal transition markers, including an increase in the expression of transcription factor SLUG. Further, novel tumour xenograft models developed in this study highlighted that SSX3 overexpression increased OC proliferation in vivo. Overall, these results highlight the importance of investigating SSX family members in OC, as biomarkers and promoters of cancer development.

Citation

Grayson, K. Investigating Synovial Sarcoma, X breakpoint proteins in ovarian cancer. (Thesis). University of Hull. https://hull-repository.worktribe.com/output/4571233

• Thesis Type: Thesis
• Deposit Date: Mar 4, 2024
• Publicly Available Date: Mar 12, 2024
• Keywords: Biomedical sciences
• Public URL: https://hull-repository.worktribe.com/output/4571233
• Additional Information: Department of Biomedical Sciences; University of Hull
• Award Date: Dec 6, 2023