Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease

• Published in: BMC cancer 2011-05, Vol.11 (1), p.185-185, Article 185
• Main Authors: Tacke, Frank, Kanig, Nicolas, En-Nia, Abdelaziz, Kaehne, Thilo, Eberhardt, Christiane S, Shpacovitch, Victoria, Trautwein, Christian, Mertens, Peter R
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Biomarkers, Tumor - blood; cancer screening; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - complications; Chronic Disease; Cold shock proteins; Female; Genetic aspects; hepatocellular carcinoma; Humans; Inflammation - blood; Liver; Liver cirrhosis; Liver Diseases - blood; Liver Diseases - complications; Liver Neoplasms - blood; Liver Neoplasms - complications; liver transplantation; Male; Middle Aged; Molecular Sequence Data; Physiological aspects; Renal Insufficiency - blood; Risk factors; Sensitivity and Specificity; Sequence Alignment; serum markers; Transplantation; Y-Box-Binding Protein 1 - blood; Young Adult
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-11-185

Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases. We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n=33), patients with non-cancerous, mostly inflammatory diseases (n=60), hepatocellular carcinoma (HCC; n=25) and advanced solid tumors (n=20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation. We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients. Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should therefore be evaluated in larger prospective studies.