SOX11 as a cancer biomarker - Expression and regulatory studies in B-cell lymphomas and ovarian cancer

Abstract: It is estimated that one third of all people in Sweden will be diagnosed with cancer during their lifetime. The outcome for a specific patient is related to early and correct diagnosis, and prediction of effective treatment regimens. Biomarkers are molecules that can aid the clinician in such decisions regarding diagnosis, prognosis and therapy. In this thesis, based on five original papers, the role of SOX11 as a novel diagnostic biomarker in MCL and prognostic biomarker in ovarian cancer is presented. In addition, it is demonstrated how antibodies against such cancer biomarkers, including SOX11, are generated and used in various applications. Expression of SOX11 in MCL is herein shown to be independent of Cyclin D1 and able to distinguish MCL from common morphological simulators. Furthermore, the prognostic relevance of SOX11 also for non-haematological disease is confirmed as expression of SOX11 in high-grade ovarian cancer relates to survival. The functional role for SOX11 is further demonstrated for expressing malignancies, as it appears to be a negative regulator of cellular growth in vitro, possibly by inducing expression of tumour suppressors. An example of the underlying regulatory mechanism for SOX11 expression in cancer is provided as the methylation status of its CpG promoter correlates to expression in lymphomas and ovarian cancers. DNA hyper methylation commonly represses genes in neoplastic cells and has the potential to be detected in blood as a diagnostic test of methylated malignancies.