Identification of cyclin B1 and Sec62 as biomarkers for recurrence in patients with HBV-related hepatocellular carcinoma after surgical resection.
BACKGROUND
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Frequent tumor recurrence after surgery is related to its poor prognosis. Although gene expression signatures have been associated with outcome, the molecular basis of HCC recurrence is not fully understood, and there is no method to predict recurrence using peripheral blood mononuclear cells (PBMCs), which can be easily obtained for recurrence prediction in the clinical setting.


METHODS
According to the microarray analysis results, we constructed a co-expression network using the k-core algorithm to determine which genes play pivotal roles in the recurrence of HCC associated with the hepatitis B virus (HBV) infection. Furthermore, we evaluated the mRNA and protein expressions in the PBMCs from 80 patients with or without recurrence and 30 healthy subjects. The stability of the signatures was determined in HCC tissues from the same 80 patients. Data analysis included ROC analysis, correlation analysis, log-lank tests, and Cox modeling to identify independent predictors of tumor recurrence.


RESULTS
The tumor-associated proteins cyclin B1, Sec62, and Birc3 were highly expressed in a subset of samples of recurrent HCC; cyclin B1, Sec62, and Birc3 positivity was observed in 80%, 65.7%, and 54.2% of the samples, respectively. The Kaplan-Meier analysis revealed that high expression levels of these proteins was associated with significantly reduced recurrence-free survival. Cox proportional hazards model analysis revealed that cyclin B1 (hazard ratio [HR], 4.762; p = 0.002) and Sec62 (HR, 2.674; p = 0.018) were independent predictors of HCC recurrence.


CONCLUSIONS
These results revealed that cyclin B1 and Sec62 may be candidate biomarkers and potential therapeutic targets for HBV-related HCC recurrence after surgery.
Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
Li
L
Weng
Juan
J
Du
Qinghui
Q
Zhou
Binbin
B
Cheng
Jun
J
Li
Denghai
D
Zhang
Changquan
C
Ling
D000328:Adult; D000368:Aged; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000601:surgery / Q000821:virology; D016000:Cluster Analysis; D056744:Cyclin B1 / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006515:Hepatitis B virus; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000601:surgery / Q000821:virology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D044767:Ubiquitin-Protein Ligases
D014408:Biomarkers, Tumor; D056744:Cyclin B1; D051034:Inhibitor of Apoptosis Proteins; D026901:Membrane Transport Proteins; C103676:SEC62 protein, human; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases