Abstract
Simple SummaryA high percentage of patients who undergo surgical resection for hepatocellular carcinoma (HCC) experience recurrence. Therefore, identification of accurate molecular markers for predicting recurrence of HCC is important. We analyzed recurrence and non-recurrence HCC tissues using two public omics datasets comprising microarray and RNA-sequencing and found novel gene signatures associated with recurrent HCC. These molecules might be used to not only predict for recurrence of HCC but also act as potential prognostic indicators for patients with HCC.Hepatocellular carcinoma (HCC) has a high rate of cancer recurrence (up to 70%) in patients who undergo surgical resection. We investigated prognostic gene signatures for predicting HCC recurrence using in silico gene expression analysis. Recurrence-associated gene candidates were chosen by a comparative analysis of gene expression profiles from two independent whole-transcriptome datasets in patients with HCC who underwent surgical resection. Five promising candidate genes, CETN2, HMGA1, MPZL1, RACGAP1, and SNRPB were identified, and the expression of these genes was evaluated using quantitative reverse transcription PCR in the validation set (n = 57). The genes CETN2, HMGA1, RACGAP1, and SNRPB, but not MPZL1, were upregulated in patients with recurrent HCC. In addition, the combination of HMGA1 and MPZL1 demonstrated the best area under the curve (0.807, 95% confidence interval [CI] = 0.681–0.899) for predicting HCC recurrence. In terms of clinicopathological correlation, CETN2, MPZL1, RACGAP1, and SNRPB were upregulated in patients with microvascular invasion, and the expression of MPZL1 and SNRPB was increased in proportion to the Edmonson tumor differentiation grade. Additionally, overexpression of CETN2, HMGA1, and RACGAP1 correlated with poor overall survival (OS) and disease-free survival (DFS) in the validation set. Finally, Cox regression analysis showed that the expression of serum alpha-fetoprotein and RACGAP1 significantly affected OS, whereas platelet count, microvascular invasion, and HMGA1 expression significantly affected DFS. In conclusion, HMGA1 and RACGAP1 may be potential prognostic biomarkers for predicting the recurrence of HCC after surgical resection.
Highlights
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer-related mortality worldwide [1]
To identify novel gene signatures for detecting recurrence in HCC patients who underwent surgical resection, we analyzed gene expression profiles using two different datasets analyzed by microarray and RNA sequencing (RNA-seq)
Gene ontology (GO) analysis demonstrated that 981 Differentially Expressed Genes (DEGs) were associated with HCC biological processes such as the Wnt signaling pathway, angiogenesis, and blood coagulation (Figure 1E)
Summary
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer-related mortality worldwide [1]. It is important to identify molecular markers that accurately predict recurrence and prognosis after HCC resection. RNA sequencing (RNA-seq) and microarray are two of the most commonly used high-throughput technologies for transcriptome profiling, and characteristic molecular gene signatures identified by these techniques could potentially be used as biomarkers to predict the recurrence of HCC. A five-gene signature (including FKBP11, SCRIB, SLC38A2, SORBS2, and STAB2) has been reported as a predictive marker for recurrence-free survival of HCC [10]. A long noncoding RNA (lncRNA) signature consisting of six lncRNAs (MSC-AS1, POLR2J4, EIF3J-AS1, SERHL, RMST, and PVT1) was significantly associated with recurrence-free survival of HCC in the TCGA cohort [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
