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

Abstract

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.

Unraveling the underlying pathogenic factors driving nonalcoholic steatohepatitis and hepatocellular carcinoma: an in-depth analysis of prognostically relevant gene signatures in hepatocellular carcinoma

“…YBX1 participates in diverse biological processes and possesses the capacity to modulate a broad spectrum of genes that govern cell proliferation, cell viability, resistance to drugs, and instability of chromatin [ 86 ]. Karyopherin α2 (KPNA2), a protein implicated in the conventional pathway of nuclear protein transportation, has been observed in many instances of cancer, including HCC [ 87 , 88 ], Nevertheless, the exact molecular mechanisms responsible for the function of KPNA2 are still not fully understood. Previous studies have shown that KPNA2 promotes the advancement of HCC by interfering with the cell cycle and increasing the expression of CCNB2 (cyclin B2)/CDK1 (cyclin-dependent kinase 1).…”