Research Paper Volume 11, Issue 14 pp 5158—5172

The diagnostic and prognostic role of RhoA in hepatocellular carcinoma

Yi Bai 1, *, , Fucun Xie 1, *, , Fei Miao 2, *, , Junyu Long 1, , Shan Huang 3, , Hanchun Huang 1, , Jianzhen Lin 1, , Dongxu Wang 1, , Xu Yang 1, , Jin Bian 1, , Jinzhu Mao 1, , Xi Wang 3, , Yilei Mao 1, , Xinting Sang 1, , Haitao Zhao 1, ,

  • 1 Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
  • 2 Department of Statistics, Tianjin University of Finance and Economics Pearl River College, Tianjin, China
  • 3 Department of Immunology, Beijing Key Laboratory for Cancer Invasion and Metastasis, Advanced Innovation Center for Human Brain Protection, School of Basic Medical Sciences, Capital Medical University, Beijing, China
* Equal contribution.

received: March 6, 2019 ; accepted: July 16, 2019 ; published: July 22, 2019 ;

https://doi.org/10.18632/aging.102110
How to Cite

Copyright © 2019 Bai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The aim of this study was to investigate the expression level of Ras homolog gene family, member A (RhoA) in patients with hepatocellular carcinoma (HCC) and to investigate the prognostic and diagnostic value of RhoA. Data mining from various data bases and wet experiments on samples from Peking Union Medical College Hospital showed that RhoA mRNA and protein expression were significantly higher in the HCC tissues than in the normal tissues. Higher expression at both the mRNA and protein levels was associated with a poorer prognosis. High sensitivity (92.5%) and specificity (90.0%) were observed in the diagnostic model based on protein level rather than mRNA level. RhoA expression was modulated by genetic amplification. The lysosome, pathogenic Escherichia coli infection, purine metabolism and pyrimidine metabolism pathways were mainly enriched in the high RhoA level group, while the hedgehog signaling, linoleic acid metabolism, olfactory transduction and taste transduction pathways were enriched in the low RhoA level group. RhoA is commonly upregulated in HCC tissues, and its expression at both the mRNA and protein levels is associated with poor prognosis. Notably, RhoA protein levels serve as a diagnostic biomarker for HCC.

Abbreviations

AFP: alpha-fetoprotein; BMI: body mass index; CAMS: Chinese Academy of Medical Sciences; CCLE: Cancer Cell Line Encyclopedia; CDC42: cell division cycle 42; CT: computer tomography; DKK1: dickkopf-1; ECT2: epithelial cell transforming sequence 2; FFPE: formalin-fixed paraffin-embedded; GAPs: GTPase-activating proteins; GDIs: guanine nucleotide dissociation inhibitors; GEFs: guanine nucleotide exchange factors; GEO: Gene Expression Omnibus; GEPIA: Gene Expression Profiling Interactive Analysis; GPC3: glypican-3; GSE: genomic spatial event; GSEA: Gene Set Enrichment Analysis; GTEx: Genotype-Tissue Expression; GTP: guanosine triphosphate; HCC: hepatocellular carcinoma; HPA: Human Protein Atlas; IHC: immunohistochemistry; KEGG: Kyoto Encyclopedia of Genes and Genomes; LIHC: liver hepatocellular carcinoma; MRI: magnetic resonance imaging; OS: overall survival; P-RhoA: phosphorylated RhoA; PUMCH: Peking Union Medical College Hospital; qPCR: quantitative polymerase chain reaction; RAC1: Ras-related C3 botulinum toxin substrate 1; RACGAP1: Rac GTPase-activating protein 1; RhoA: Ras homolog gene family, member A; SDs: standard deviations; SND1: Staphylococcal nuclease domain-containing protein 1; SNPs: single nucleotide polymorphisms; TCGA: The Cancer Genome Atlas; UI: ultrasound imaging.