Abstract 2798: A multi-biomarker panel of nuclear transport proteins with potential as novel secreted cancer biomarkers

Abstract

Abstract Members of the nuclear transport protein family have been identified to have increased expression in many cancer types, with some being investigated as anticancer therapeutic targets. Recently, individual nuclear transport proteins have been reported to be secreted by cancer cells and found in the serum of cancer patients. In this study we investigated a multi-marker panel of nuclear transport proteins for their potential as diagnostic markers for cancer using cervical and oesophageal cancer as disease models. Mass spectrometry identified ten nuclear transport proteins in the secretome and exosomes of cultured cancer cells which was confirmed by western blot analysis showing increased secreted levels in cancer cells compared to normal. The presence of multiple nuclear transport proteins was confirmed in patient serum using ELISA assays which revealed significantly increased levels of KPNβ1, CRM1, CAS, IPO5 and TNPO1 in cervical and oesophageal cancer patient serum compared to non-cancer controls. Significantly elevated KPNα2 and RAN levels were also identified in oesophageal cancer serum samples. Logistics regression analyses revealed IPO5 and TNPO1 to be the best performing individual candidate biomarkers in discriminating between cancer cases and controls. The combination of KPNβ1, CRM1, KPNα2, CAS, RAN, IPO5 and TNPO1 as a multi-marker panel of biomarkers had the highest diagnostic capacity with an area under the curve (AUC) of 0.944 and 0.963, for cervical cancer and oesophageal cancer, and sensitivity of 92.5% at 86.8% specificity and 95.3% sensitivity at 87.5% specificity, respectively. These results suggest that nuclear transport proteins have potential as diagnostic biomarkers for cervical and oesophageal cancers, with a multi-panel protein combination being the best predictor. Citation Format: Pauline van der Watt, Michael Okpara, Andrew Wishart, Iqbal Parker, Nelson Soares, Jonathan Blackburn, Virna D. Leaner. A multi-biomarker panel of nuclear transport proteins with potential as novel secreted cancer biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2798.