Academic Journal

Pathophysiological Implications of Urinary Peptides in Hepatocellular Carcinoma

التفاصيل البيبلوغرافية
العنوان: Pathophysiological Implications of Urinary Peptides in Hepatocellular Carcinoma
المؤلفون: Ayman Bannaga, Jochen Metzger, Torsten Voigtländer, Martin Pejchinovski, Maria Frantzi, Thorsten Book, Sean James, Kishore Gopalakrishnan, Harald Mischak, Michael P. Manns, Ramesh P. Arasaradnam
المصدر: Cancers; Volume 13; Issue 15; Pages: 3786
بيانات النشر: Multidisciplinary Digital Publishing Institute
سنة النشر: 2021
المجموعة: MDPI Open Access Publishing
مصطلحات موضوعية: hepatocellular carcinoma, capillary electrophoresis mass spectrometry, urinary peptides, diagnosis, prognosis
الوصف: Hepatocellular carcinoma (HCC) is known to be associated with protein alterations and extracellular fibrous deposition. We investigated the urinary proteomic profiles of HCC patients in this prospective cross sectional multicentre study. 195 patients were recruited from the UK (Coventry) and Germany (Hannover) between 1 January 2013 and 30 June 2019. Out of these, 57 were HCC patients with a background of liver cirrhosis (LC) and 138 were non-HCC controls; 72 patients with LC, 57 with non-cirrhotic liver disease and 9 with normal liver function. Analysis of the urine samples was performed by capillary electrophoresis (CE) coupled to mass spectrometry (MS). Peptide sequences were obtained and 31 specific peptide markers for HCC were identified and further integrated into a multivariate classification model. The peptide model demonstrated 79.5% sensitivity and 85.1% specificity (95% CI: 0.81–0.93, p < 0.0001) for HCC and 4.1-fold increased risk of death (95% CI: 1.7–9.8, p = 0.0005). Proteases potentially involved in HCC progression were mapped to the N- and C-terminal sequence motifs of the CE-MS peptide markers. In silico protease prediction revealed that kallikrein-6 (KLK6) elicits increased activity, whilst Meprin A subunit α (MEP1A) has reduced activity in HCC compared to the controls. Tissue expression of KLK6 and MEP1A was subsequently verified by immunohistochemistry.
نوع الوثيقة: text
وصف الملف: application/pdf
اللغة: English
Relation: https://dx.doi.org/10.3390/cancers13153786
DOI: 10.3390/cancers13153786
الاتاحة: https://doi.org/10.3390/cancers13153786
Rights: https://creativecommons.org/licenses/by/4.0/
رقم الانضمام: edsbas.EE5238CC
قاعدة البيانات: BASE