Research Paper Volume 13, Issue 4 pp 5263—5283

Value of KPNA4 as a diagnostic and prognostic biomarker for hepatocellular carcinoma

Mingxing Xu1, *, , Hao Liang2, *, , Kun Li3, *, , Shu Zhu4, *, , Zhicheng Yao2, , Ruiyun Xu1, , Nan Lin1, ,

  • 1 Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong, China
  • 2 Department of General Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong, China
  • 3 Department of Liver Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong, China
  • 4 Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong, China
* Equal contribution

Received: January 9, 2020       Accepted: November 25, 2020       Published: February 1, 2021      

https://doi.org/10.18632/aging.202447
How to Cite

Copyright: © 2021 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

It is important to identify novel biomarkers to improve hepatocellular carcinoma (HCC) diagnosis and treatment. Herein, we reported the role of karyopherin α4 (KPNA4) in HCC patients through public data mining and examined the results using clinical samples in our center. Our results revealed that KPNA4 expression level was positively correlated with the infiltration of CD8+ T cells, B cells, dendritic cells, CD4+ T cells, neutrophils and macrophages. In addition, KPNA4 expression was significantly associated with T cell exhaustion. KPNA4 mRNA and protein expression levels were significantly higher in cancerous tissue than in normal tissue. Besides, the increased expression of KPNA4 indicated poor overall survival. Univariate and multivariate Cox regression analyses showed KPNA4 could be viewed as an independent risk factor for HCC patients. Moreover, our experimental results were consistent with those obtained from bioinformatic results. These findings revealed KPNA4 may serve as a novel prognostic biomarker and a potential therapeutic target for HCC.

Abbreviations

HCC: Hepatocellular carcinoma; OS: Overall survival; KPNA4: karyopherin α4; EMT: Epithelial-mesenchymal transition; TIMER: Tumor IMmune Estimation Resource; GEPIA: Gene Expression Profiling Interactive Analysis; TCGA: The Cancer Genome Atlas; GTEX: Genotype-Tissue Expression; HPA: Human Protein Atlas; MERAV: Metabolic gEne RApid Visualizer; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; WebGestalt: Web-based GEne SeT AnaLysis Toolkit; qRT-PCR: Quantitative reverse transcription-PCR; SNCA: Somatic copy number alterations; BMI: Body mass index; HR: Hazard ratio; CI: Confidence interval; TB: Total bilirubin; GSEA: Gene set enrichment analysis; CDK2: Cyclin-dependent kinase 2; MAPK1: Mitogen-activated protein kinase 1; ATM: Ataxia-telangiectasia mutated; CHEK1: Checkpoint kinase 1; ROC: Receiver operating characteristic; RFA: Radiofrequency ablation; NLS: Nuclear localization signal.