Autoantibodies against HSF1 and CCDC155 as Biomarkers of Early-Stage, High-Grade Serous Ovarian Cancer

Amy L. Wilson, Laura R. Moffitt, Nadine Duffield, Adam Rainczuk, Tom W. Jobling, Magdalena Plebanski, Andrew N. Stephens

Tumor-directed circulating autoantibodies (AAbs) are a well-established feature of many solid tumor types, and are often observed prior to clinical disease manifestation. As such, they may provide a good indicator of early disease development. We have conducted a pilot study to identify novel AAbs as markers of early stage HGSOCs. A rare cohort of patients with early (FIGO stage Ia-c) HGSOCs for IgG, IgA and IgM-mediated AAb reactivity using high content protein arrays (containing 9184 individual proteins). AAb reactivity against selected antigens was validated by ELISA in a second, independent cohort of individual patients. A total of 184 antigens were differentially detected in early-stage HGSOC patients compared to all other patient groups assessed. Amongst the six most highly detected "early stage" antigens, anti-IgA AAbs against HSF1 and anti-IgG AAbs CCDC155 (KASH5; nesprin 5) were significantly elevated in patients with early-stage malignancy. Receiver operating characteristic (ROC) analysis suggested that AAbs against HSF1 provided better detection of early-stage malignancy than CA125 alone. Combined measurement of anti-HSF1, anti-CCDC155 and CA125 also improved efficacy at higher sensitivity. The combined measurement of anti-HSF1, anti-CCDC155 and CA125 may be useful for early stage HGSOC detection. This is the first study to specifically identify AAbs associated with early-stage HGSOC. The presence and high frequency of specific AAbs in early stage cancer patients warrants a larger scale examination to define their value for early disease detection at primary diagnosis and/or recurrence.