Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma

PeerJ

article

Jinzhong Zhang¹  Xiuzhi Zhang¹  Lingxiao Wang¹  Chunyan Kang¹  Ningning Li¹  Zhefeng Xiao²  Liping Dai³ 

[1] Department of Pathology, Henan Medical College, Zhengzhou, Henan Province;NHC Key Laboratory of Cancer Proteomics, Xiangya Hospital, Central South University, Changsha, Hunan Province;Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province

关键词: Hepatocellular carcinoma;    KPNA2;    Genetic and epigenetic regulation;    Prognosis;    Fatty acid metabolism;    Immunoregulation;   

DOI  :  10.7717/peerj.12197

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Dysregulation and prognostic roles of Karyopherin α2 (KPNA2) were reported in many malignancies including hepatocellular carcinoma (HCC). A multi-omics analysis of KPNA2 is needed to gain a deeper understanding of its multilevel molecular characteristics and provide novel clues for HCC diagnosis, prognosis, and target therapy. Herein multi-omic alterations of KPNA2 were analyzed at genetic, epigenetic, transcript, and protein levels with evaluation of their relevance with clinicopathological features of HCC by integrative analyses. The significant correlations of KPNA2 expression with its gene copy number variation (CNV) and methylation status were shown through Spearman correlation analyses. With Cox regression, Kaplan-Meier survival, and receiver operating characteristic (ROC) analyses, based on the factors of KPNA2 CNV, methylation, expression, and tumor stage, risk models for HCC overall survival (OS) and disease-free survival (DFS) were constructed which could discriminate the 1-year, 3-year, and 5-year OS/DFS status effectively. With Microenvironment Cell Populations-counter (MCP-counter), the immune infiltrations of HCC samples were evaluated and their associations with KPNA2 were shown. KPNA2 expression in liver was found to be influenced by low fat diet and presented significant correlations with fatty acid metabolism and fatty acid synthase activity in HCC. KPNA2 was detected lowered in HCC patient’s plasma by enzyme linked immunosorbent assay (ELISA), consistent with its translocation to nuclei of HCC cells. In conclusion, KPNA2 multilevel dysregulation in HCC and its correlations with immune infiltration and the fatty acid metabolism pathway indicated its multiple roles in HCC. The clinicopathological significance of KPNA2 was highlighted through the in-depth analyses at multilevels.

【 授权许可】

CC BY