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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Frank Tacke, Nicolas Kanig, Abdelaziz En-Nia, Thilo Kaehne, Christiane S Eberhardt, Victoria Shpacovitch, Christian Trautwein, Peter R Mertens
• Journal: BMC cancer (BMC Cancer) Vol. 11 Pg. 185 (May 20 2011) ISSN: 1471-2407 [Electronic] England
• PMID: 21595987 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Y-Box-Binding Protein 1

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Amino Acid Sequence
• Biomarkers, Tumor (blood)
• Carcinoma, Hepatocellular (blood, complications)
• Chronic Disease
• Female
• Humans
• Inflammation (blood)
• Liver Diseases (blood, complications)
• Liver Neoplasms (blood, complications)
• Male
• Middle Aged
• Molecular Sequence Data
• Renal Insufficiency (blood)
• Sensitivity and Specificity
• Sequence Alignment
• Y-Box-Binding Protein 1 (blood)
• Young Adult