Novel Gene Signatures as Prognostic Biomarkers for Predicting the Recurrence of Hepatocellular Carcinoma

Cancers

Geum Ok Baek¹  Ju A Son¹  Soon Sun Kim¹  Jae Youn Cheong¹  Moon Gyong Yoon¹  Jung Woo Eun¹  Hyo Jung Cho¹  Hye Ri Ahn¹  Donglim You¹  Jung Hwan Yoon²  Suk Woo Nam² 

[1] Department of Gastroenterology, School of Medicine, Ajou University, Suwon 16499, Korea;Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;

关键词: biomarker;    prognosis;    hepatocellular carcinoma;    recurrence;   

DOI  :  10.3390/cancers14040865

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown