Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Int J Cancer. 2022 Jan 15;150(2):347-361. doi: 10.1002/ijc.33832. Epub 2021 Oct 20.
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.
先前的研究已经确定，核转运蛋白家族的某些成员在癌细胞中的表达增加。最近，已经有报道称某些核转运蛋白被细胞分泌，并在血清中发现。我们的研究旨在探讨癌细胞分泌的多种核转运蛋白的水平，并确定它们作为宫颈癌和食管癌诊断标志物的潜力。质谱法在培养的癌细胞的分泌组和外泌体中鉴定出 10 种核转运蛋白，Western blot 分析证实癌细胞中分泌的核转运蛋白水平高于正常细胞。为了研究它们在患者血清中的存在情况，进行了酶联免疫吸附试验，结果显示宫颈癌和食管癌患者血清中 KPNβ1、CRM1、CAS、IPO5 和 TNPO1 的水平明显升高，与非癌症对照相比。还发现食管癌血清样本中 KPNα2 和 RAN 水平显著升高。逻辑回归分析显示，IPO5 和 TNPO1 是区分癌症病例和对照的最佳表现候选生物标志物。KPNβ1、CRM1、KPNα2、CAS、RAN、IPO5 和 TNPO1 的组合作为一组生物标志物具有最高的诊断能力，其曲线下面积分别为 0.944 和 0.963，用于宫颈癌和食管癌，敏感性分别为 92.5%，特异性为 86.8%，特异性为 95.3%，特异性为 87.5%。这些结果表明，核转运蛋白具有作为宫颈癌和食管癌诊断生物标志物的潜力，蛋白质家族成员的组合是最佳预测因子。
