Rationale: Ovarian cancer has the highest mortality rate within all gynaecological cancers. Most undifferentiated serous cancers (75%) present with advanced FIGO stage, characterised by a 5-year survival rate of only 30%. To improve this outcome, there is an urgent need to further elucidate the underlying molecular processes of ovarian cancer development and progression to aid in the identification of reliable biomarkers with diagnostic, prognostic and therapeutic potential. The IQ motif containing GTPase activating protein 1 (IQGAP1) is involved in cell proliferation, adhesion, migration and angiogenesis. Dysregulated protein expression was observed in various cancers including gastric, colon and endometrial cancer. Additionally, we previously identified IQGAP1 as a marker of progression and survival in high grade glioma patients. We hypothesised that in ovarian cancer, IQGAP1 expression would correlate with disease progression.
Methods: IQGAP1 protein expression and cellular localisation was examined in a cohort of 721 ovarian cancer patients and healthy controls using immunohistochemistry (IHC). Additionally, we screened a panel of ovarian cancer cell lines by RT-qPCR, Western Blotting and IHC to ascertain IQGAP1 expression in vitro.
Results: Strong IQGAP1 protein expression was observed within the cell membrane and was also present to a lesser degree within the cytoplasm, in both tissues and cell lines. Over-expression of IQGAP1 was noted in metastatic tumours when compared to their matched primary lesion. Within the cell lines, no significant alteration was observed at the mRNA or total protein level; however, increased plasma membrane expression of IQGAP1 was associated with the more aggressive serous subtype. IQGAP1 expression was also found to correlate significantly to members of the Wnt-signalling pathway.
Conclusions: This study indicates that IQGAP1 is a potential new marker for ovarian cancer progression to metastasis, and suggests that IQGAP1-targeted therapies may be useful for treatment of advanced ovarian cancers.