Skip to Content
Merck
  • Nuclear transport proteins are secreted by cancer cells and identified as potential novel cancer biomarkers.

Nuclear transport proteins are secreted by cancer cells and identified as potential novel cancer biomarkers.

International journal of cancer (2021-10-01)
Pauline J van der Watt, Michael O Okpara, Andrew Wishart, M Iqbal Parker, Nelson C Soares, Jonathan M Blackburn, Virna D Leaner
ABSTRACT

Previous studies have identified increased expression of members of the nuclear transport protein family in cancer cells. Recently, certain nuclear transport proteins have been reported to be secreted by cells and found in the serum. The aims of our study were to investigate the levels of multiple nuclear transport proteins secreted from cancer cells, and to determine their potential as diagnostic markers for cervical and oesophageal cancer. Mass spectrometry identified 10 nuclear transport proteins in the secretome and exosomes of cultured cancer cells, and Western blot analysis confirmed increased secreted levels in cancer cells compared to normal. To investigate their presence in patient serum, enzyme-linked immunosorbent assays were performed and 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 panel of biomarkers had the highest diagnostic capacity with an area under the curve 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 combination of protein family members being the best predictor.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Transportin 1 antibody, Mouse monoclonal, clone D45, purified from hybridoma cell culture
Sigma-Aldrich
Anti-Importin 5 (C-terminal) antibody produced in rabbit, ~1.0 mg/mL, affinity isolated antibody
Sigma-Aldrich
Anti-Ran antibody,Mouse monoclonal, clone ARAN1, purified from hybridoma cell culture
Sigma-Aldrich
Monoclonal Anti-CSE1L antibody produced in mouse, clone 3D8, purified immunoglobulin, buffered aqueous solution