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Hepatocellular carcinoma (HCC) is a common tumor across the globe with a high mortality rate. ZSCAN20 is a ZNF transcription factor, a key determinant of gene expression. Nonetheless, the mechanism of ZSCAN20 as a potential clinical biomarker and therapeutic target for HCC is not understood. Here, TIMER, TCGA, ICGC databases and immunohistochemical (IHC) and Western Blot found ZSCAN20 mRNA and protein levels were upregulated. Additionally, Kaplan-Meier Plotter, GEPIA and TCGA databases showed high ZSCAN20 expression was related to the short survival time of HCC patients. Multivariate Cox analysis exposed that ZSCAN20 can act as an independent prognostic factor. We observed methylation level of ZSCAN20 was associated with the clinicopathological characteristics and prognosis of HCC patients through UALCAN. Furthermore, enrichment examination exposed functional association between ZSCAN20 and cell cycle, immune infiltration. Functional experiments showed that interference with ZSCAN20 significantly reduced the invasion, migration and proliferation abilities of HCC cells. An immune infiltration analysis showed that ZSCAN20 was associated with immune cells, particularly T cells. The expression of ZSCAN20 was correlated with poor prognosis in the Regulatory T-cell. And Real-Time RT-PCR analysis found interference with ZSCAN20 significantly reduced the expression of some chemokines. Finally, the TCGA and ICGC data analysis suggested that the ZSCAN20 expression was greatly related to m6A modifier related genes. In conclusion, ZSCAN20 can serve as a prognostic biomarker for HCC and provide clues about cell cycle, immune infiltration, and m6A modification.

No abstract

Purpose Hepatocellular carcinoma (HCC) is a prevalent tumor with high morbidity, and an unfavourable prognosis. FARSB is an aminoacyl tRNA synthase, and plays a key role in protein synthesis in cells. Furthermore, previous reports have indicated that FARSB is overexpressed in gastric tumor tissues and is associated with a poor prognosis and tumorigenesis. However, the function of FARSB in HCC has not been studied. Results The results showed that FARSB mRNA and protein levels were upregulated in HCC and were closely related to many clinicopathological characteristics. Besides, according to multivariate Cox analysis, high FARSB expression was linked with a shorter survival time in HCC and may be an independent prognostic factor. In addition, the methylation level was negatively associated with the expression of FARSB. Furthermore, enrichment analysis showed that FARSB was related to the cell cycle. And TIMER analysis revealed that the FARSB expression was closely linked to tumor purity and immune cell infiltration. The TCGA and ICGC data analysis suggested that FARSB expression is greatly related to m6A modifier related genes. Potential FARSB-related ceRNA regulatory networks were also constructed. What’s more, based on the FARSB-protein interaction network, molecular docking models of FARSB and RPLP1 were constructed. Finally, drug susceptibility testing revealed that FARSB was susceptible to 38 different drugs or small molecules. Conclusion FARSB can serve as a prognostic biomarker for HCC and provide clues about immune infiltration, and m6A modification.

Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer, with a high morbidity and low survival rate. Rho GTPase activating protein 39 (ARHGAP39) is a crucial activating protein of Rho GTPases, a novel target in cancer therapy, and it was identified as a hub gene for gastric cancer. However, the expression and role of ARHGAP39 in hepatocellular carcinoma remain unclear. Accordingly, the cancer genome atlas (TCGA) data were used to analyze the expression and clinical value of ARHGAP39 in hepatocellular carcinoma. Further, the LinkedOmics tool suggested functional enrichment pathways for ARHGAP39. To investigate in depth the possible role of ARHGAP39 on immune infiltration, we analyzed the relationship between ARHGAP39 and chemokines in HCCLM3 cells. Finally, the GSCA website was used to explore drug resistance in patients with high ARHGAP39 expression. Studies have shown that ARHGAP39 is highly expressed in hepatocellular carcinoma and relevant to clinicopathological features. In addition, the overexpression of ARHGAP39 leads to a poor prognosis. Besides, co-expressed genes and enrichment analysis showed a correlation with the cell cycle. Notably, ARHGAP39 may worsen the survival of hepatocellular carcinoma patients by increasing the level of immune infiltration through chemokines. Moreover, N6-methyladenosine (m 6 A) modification-related factors and drug sensitivity were also found to be associated with ARHGAP39. In brief, ARHGAP39 is a promising prognostic factor for hepatocellular carcinoma patients that is closely related to cell cycle, immune infiltration, m6A modification, and drug resistance.