COVID-19 ACE2 related to hepatocellular carcinoma in single cell analyses and immuno-cancer microenvironment infiltrated with macrophage

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is the second leading cause of malignancy-related mortality and the fifth most common worldwide. Immuno-cancer microenvironment (ICME) was highlighted recently because scientists want to unlock the detailed mechanism in carcinogenesis pathway and find the novel interactions in ICME. Besides, single cell analysis could mitigate the interrupted signals between cells and tissues. On the other hand, COVID-19 angiotensin I converting enzyme (ACE) previously was reported associated with cancer. However, the robust association between COVID-19 and HCC ICME is still unaddressed. Aim(s) We plan to investigate the COVID-19 ACE relevant genes to HCC ICME regarding survival. Method(s) We used Reactome for COVID-19 ACE gene pathway mapping and explored the positive relevant gene expression. DISCO website was applied for single cell analyses using the above-collected genes from Reactome. Finally, we implanted the biomedical informatics into TIMER 2.0 for ICME survival analyses. Result(s) In Fig. 1, the gene-gene interaction mapping was shown. We collected 13 genes (CPB2, ACE2, AGT, MME, ANPEP, CPA3, ENPEP, GZMH, CTSZ, CTSD, CES1, ATP6AP2, and AOPEP) for further single cell relevant analyses, in Table 1, with detailed expression level (TPM). Among the above 13 genes, AGT, GZMH, CTSZ, CTSD, CES1, and ATP6AP2 were strongly expressed in liver tissue. We then applied the initial 13 genes to TIMER 2.0 for HCC ICME 2-year survival analyses. CPA3 and GZMH low expressions with high macrophage infiltration in HCC ICME showed significantly worse 2-year cumulative survival [hazard ratio (HR)CPA3 2.21, p-value 0.018;GZMH 2.07, p-value 0.0341]. ACE2, CPB2, AGT, MME, ANPEP, ENPEP, CTSZ, CTSD, CES1, and ATP6AP2 high expressions with high macrophage infiltration in HCC ICME revealed significantly worse 2-year cumulative survival. Conclusion(s) We demonstrate that ACE2 was strongly associated with HCC clinical survival with macrophage infiltration. However, the bidirectional translational roles about ACE2 relevant genes in HCC should be documented.