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. 2020;28(3):341-350.
doi: 10.3233/CBM-190507.

Expression of FOXM1 and Aurora-A predicts prognosis and sorafenib efficacy in patients with hepatocellular carcinoma

Wen-Lung Su  1 , Shih-Chang Chuang  2 , Yu-Chu Wang  2 , Lin-An Chen  3 , Jian-Wei Huang  2 , Wen-Tsan Chang  2 , Shen-Nien Wang  2 , King-Teh Lee  2 , Chang-Shen Lin  4 , Kung-Kai Kuo  2
Affiliations

Expression of FOXM1 and Aurora-A predicts prognosis and sorafenib efficacy in patients with hepatocellular carcinoma

Wen-Lung Su et al. Cancer Biomark. 2020.

Abstract

Background: Effective prognostic biomarkers and powerful target-therapeutic drugs are needed for improving the treatment of Hepatocellular carcinoma (HCC).

Objective: This study aimed to evaluate the expression of FOXM1 and Aurora-A and their prognostic value in HCC.

Methods: We determined the differentially expressed genes signature in HCC using the Gene Set Enrichment Analysis (GSEA), and then evaluated the expression of FOXM1 and Aurora-A in TCGA and KMUH cohort. Associations between co-expression of FOXM1 and Aurora-A and clinical variables were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated with different FOXM1 and Aurora-A expression status.

Results: FOXM1-related gene sets were mostly associated with cell cycle regulation in HCC tissues. We found a positive correlation between the expression of FOXM1 and Aurora-A. Overexpression of FOXM1 and Aurora-A was associated with larger tumor size, advanced stage, higher grade, and double-positive for HBV and HCV. The coordinated overexpression of FOXM1 and Aurora-A was the most significant independent prognostic factor for OS and RFS. Furthermore, the concomitant high expression of FOXM1 and Aurora-A predicted the worst OS of sorafenib-treated patients with HCC.

Conclusions: The co-expression of FOXM1 and Aurora-A could be a reliable biomarker to predict the sorafenib response and prognosis of HCC patients.

Keywords: Aurora-A; FOXM1; hepatocellular carcinoma (HCC); sorafenib.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Supplementary Fig. 1.
Supplementary Fig. 1.
Effect of FOXM1 knockdown on the expression of cell cycle-regulating proteins in HCC cells. HepG2 and Hep3B cells were transfected with control siRNA or with FOXM1 siRNA. The expression of the indicated cell cycle-regulating proteins was analyzed by western blotting.
Fig. 1.
Fig. 1.
FOXM1 expression is positively correlated with Aurora-A expression in human HCC. (a) The expression of FOXM1 and Aurora-A in HCC and adjacent liver tissues by transcriptome sequencing from the TCGA dataset (Left). The expression levels of the FOXM1 and Aurora-A mRNAs were validated in 40 paired HCC from KMUH using RT-qPCR (Right). The horizontal lines depict the mean ± S.D. (b) The level of FOXM1 and Aurora-A in HCC tissues from the TCGA and KMUH datasets and the correlation between their expression levels was analyzed using Fisher’s exact test (p< 0.001). (c) The relationship between FOXM1 and Aurora-A expression in HCC (black dot, n= 341) and adjacent liver tissues (red dot, n= 44) was analyzed using Pearson’s correlation. RSEM, RNA-seq by Expectation Maximization.
Fig. 2.
Fig. 2.
Overexpression of FOXM1 and Aurora-A are associated with poor prognosis in HCC. KaplanMeier curves of OS (Left) and RFS (Right) were estimated with different FOXM1 and Aurora-A expression status in the TCGA (n= 341) (a–b), and OS in KMUH (n= 30) datasets (c–d). KaplanMeier curves for OS (Left) and RFS (Right) among three subgroups according to FOXM1 and Aurora-A expression status in the TCGA (n= 341) (e), and OS in KMUH (n= 30) datasets (f).
Fig. 3.
Fig. 3.
FOXM1 and Aurora-A expression predict the prognosis of sorafenib-treated patients in HCC. KaplanMeier curves of overall survival probability were estimated with different FOXM1 (a), Aurora-A (b), and FOXM1/Aurora-A (c) expression status in sorafenib-treated patients obtained from the TCGA dataset (n= 29).
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