Identification of cyclin B1 and Sec62 as biomarkers for recurrence in patients with HBV-related hepatocellular carcinoma after surgical resection

Abstract

BackgroundHepatocellular 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.MethodsAccording 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.ResultsThe 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.ConclusionThese results revealed that cyclin B1 and Sec62 may be candidate biomarkers and potential therapeutic targets for HBV-related HCC recurrence after surgery.

Preferential Autoimmune Response in Prostate Cancer to Cyclin B1 in a Panel of Tumor-Associated Antigens

“…It has been reported that cyclin B1 was associated with recurrence in hepatocellular carcinoma [39], poor prognosis in gastric cancer [12], and poor survival in breast cancer [40]. Of interest in the present study was that six out of eighteen PCa patients showed the increased anti-cyclin B1 antibody after surgery.…”

Chk1-induced CCNB1 overexpression promotes cell proliferation and tumor growth in human colorectal cancer

“…[5][6][7][8][9] In parallel, evidence has showed that inhibition of CCNB1 expression renders breast cancer cells more sensitive to chemotherapy drug taxol, 10 and CCNB1 is an independent predictor of HBV-related hepatocellular carcinoma recurrence. 11 Furthermore, it has been revealed that wild-type p53 represses the transcription of CCNB1 through Sp1 transcription factor in tumor cells, 12 and the protein level of CCNB1 is undetectable in HCT116 p53 +/+ cells, while overexpressed in HCT116 p53 −/− cells. 13 These data highlight the potential pivotal roles of CCNB1 in the tumor development.…”

Identification of the transcriptional regulators by expression profiling infected with hepatitis B virus

“…The GO enrichment analysis of DCGs indicates that some GO terms, such as inflammatory response, defence response, and response to wounding, have highly significant in biological functioning. Previous studies have shown that the liver inflammatory response is the pivotal consequence of the biological behavior of HBC [28]. The reason of triggering inflammation is probably because multiple types of immune cells having defensive function may be active participator in pathogenesis of CHB [56].…”

“…One is that previous researches have shown that PBMC can provide a reporter function in solid organ diseases [26,27]. Some studies also suggested that some characteristics of genes in PBMC might be related to the pathogenesis and progression of CHB and HBV-related HCC (hepatocellular carcinoma) [28]. Another is that measuring mRNA profile associated with PBMC could be done with standard experimental facility and minimal resource utilization.…”