[Clusterin is a potential serum marker of hepatic carcinoma].

OBJECTIVE: To determine the differentially expressed serum proteins in patients with hepatoma carcinoma and identify a putative diagnostic marker. METHOD: The isobaric tags for relative and absolute quantitation (iTRAQ) labeling method and LC-MALDI-TOF/TOF MS detection method were used to quantify serum proteins in hepatocellular carcinoma patients (n =20) and healthy individuals (n =20). Real-time reverse transcription-polymerase chain reaction was used to verify the differentially expressed proteins by analyzing the corresponding mRNA expression levels in the hepatic carcinoma and healthy hepatocyte samples, as well as in 30 pairs of patient-matched hepatic carcinoma and adjacent normal tissue samples. Western blot analysis was used to verify the protein expression in hepatic carcinoma cells. RESULT: Fifty-one proteins were significantly differentially expressed between the hepatic carcinoma group and healthy controls. The iTRAQ protein profile showed that the serum level of clusterin was significantly lower in hepatoma carcinoma patients. The mRNA level of clusterin was 20-fold lower in hepatic carcinoma cells than in healthy hepatocytes, and was 2.38-fold lower in hepatoma tissues than that in adjacent normal tissues. The clusterin protein levels were significantly lower in hepatic carcinoma cells (8.06 vs normal hepatocytes: 27.81; P less than 0.01). CONCLUSION: The serum expression of clusterin is significantly decreased in both serum and tissues of hepatic carcinoma patients. The relationship between hepatic carcinoma and clusterin should be evaluated in future studies.

Diagnostic and prognostic value of MCM3 and its interacting proteins in hepatocellular carcinoma.

Aberrant DNA replication is one of the driving forces behind oncogenesis. Furthermore, minichromosome maintenance complex component 3 (MCM3) serves an essential role in DNA replication. Therefore, in the present study, the diagnostic and prognostic value of MCM3 and its interacting proteins in hepatocellular carcinoma (HCC) were investigated. By utilizing The Cancer Genome Atlas (TCGA) database, global MCM3 mRNA levels were assessed in HCC and normal liver tissues. Its effects were further analyzed by reverse transcription-quantitative PCR (RT-qPCR), western blotting and immunohistochemistry in 78 paired HCC and adjacent tissues. Functional and pathway enrichment analyses were performed using the Search Tool for the Retrieval of Interacting Genes database. The expression levels of proteins that interact with MCM3 were also analyzed using the TCGA database and RT-qPCR. Finally, algorithms combining receiver operating characteristic (ROC) curves were constructed using binary logistic regression using the TCGA results. Increased MCM3 mRNA expression with high α-fetoprotein levels and advanced Edmondson-Steiner grade were found to be characteristic of HCC. Survival analysis revealed that high MCM3 expression was associated with poor outcomes in patients with HCC. In addition, MCM3 protein expression was associated with increased tumor invasion in HCC tissues. MCM3 and its interacting proteins were found to be primarily involved in DNA replication, cell cycle and a number of binding processes. Algorithms combining ROCs of MCM3 and its interacting proteins were found to have improved HCC diagnosis ability compared with MCM3 and other individual diagnostic markers. In conclusion, MCM3 appears to be a promising diagnostic biomarker for HCC. Additionally, the present study provides a basis for the multi-gene diagnosis of HCC using MCM3.