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

Background & aims: Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. The active secretion of a family member, denoted Y-box (YB) protein–1, was recently discovered by our group. As effective screening tools for malignant diseases are warranted for high risk populations such as patients with liver cirrhosis considered for potential transplantation, we tested the clinical and diagnostic value of YB–1 protein fragment p18 (YB–1/p18) detection in blood for malignant and liver diseases in different cohorts of patients.

Patients & 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: 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. Renal function or inflammation did not influence detection of YB–1/p18 in these cohorts of patients. In 111 patients with chronic liver disease undergoing evaluation for potential liver transplant, 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 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, CA 19–9 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. YB–1/p18 may have striking clinical potential as novel tumor marker for the screening of high-risk patient populations, e.g. before liver transplantation.

HCC - Krebs - Lebertumor - Leberzirrhose - YB-1