ACE2 correlates with immune infiltrates in colon adenocarcinoma: Implication for COVID-19

Abstract

Novel coronavirus disease (COVID-19) pandemic has become a global health emergency. It has been reported that a few conditions, including cancer, predispose individuals to SARS-CoV-2 infection and severe form of COVID-19. These findings led us to evaluate the susceptibility of colon adenocarcinoma (COAD) patients to SARS-CoV-2 infection by investigating ACE2 expression in their tumor tissues. The expression analysis revealed that both mRNA and protein levels of ACE2 had increased in colon cancer samples than normal group. Next, the prognosis analysis has indicated that the upregulation of ACE2 was not correlated with patient survival outcomes. Further assessment displayed the hypomethylation of the ACE2 gene promoter in COAD patients. This methylation status has a strong negative correlation with ACE2 gene expression. The functional enrichment analysis of the genes that had similar expression patterns with ACE2 in colon cancer tissues demonstrated that they mainly enriched in Vitamin digestion and absorption pathway. Finally, we found that ACE2 gene expression had a significant association with the immune cell infiltration levels in COAD patients. In conclusion, it has plausible that COAD patients are more likely to be infected with SARS-CoV-2 and experience severe injuries. Moreover, COVID-19 would bring unfavorable survival outcomes for patients with colon cancer by way of immune cell infiltration linked process. The present study highlights the importance of preventiveactionsfor COAD patients during the COVID-19 pandemic.

Keywords: COVID-19; Colon cancer; Immune cell infiltration; Prognosis; Susceptibility.

Fig. 1

The expression analysis of the ACE2 in colon cancer. We demonstrated the expression level of the ACE2 gene in multiple cancers (A), especially in COAD tissues and corresponding normal tissues (B), using the GEPIA2 database. The protein expression levels of ACE2 in normal tissue and colon cancer tissue were also obtained by the UALCAN database (C). ACE2: angiotensin-converting enzyme 2; COAD: Colon Adenocarcinoma; GEPIA: Gene Expression Profiling Interactive Analysis.

Fig. 2

Survival analysis of colon cancer patients based on ACE2 expression. We used the OnoLnc, and GENT2 databases to assess the overall survival analyses Based on the TCGA-COAD cohort data (A) and survival data of multiple GEO datasets (B), respectively. A log rank p-value < 0.05 was considered statistically significant. ACE2: angiotensin-converting enzyme 2; GENT2: Gene Expression database of Normal and Tumor tissues 2; TCGA: The Cancer Genome Atlas Program; COAD: Colon Adenocarcinoma.

Fig. 3

The promoter methylation status of the ACE2 gene in COAD. DNA methylation analysis by the UALCAN showed a lower methylation level for the ACE2 gene in COAD (A). We also detected the hypomethylation of the ACE2 promoter in COAD (B), and a strong negative correlation between the mRNA expression and the methylation status of the ACE2 gene in COAD (C, D), using the DNMIVD database. A p-value < 0.05 was defined as a threshold for this analysis. ACE2: angiotensin-converting enzyme 2; COAD: Colon Adenocarcinoma; DNMIVD: DNA Methylation Interactive Visualization Database.

Fig. 4

Data of GO and KEGG enrichment analysis. The top 100 genes with similar expression pattern with ACE2 in TCGA-COAD, the enriched information of biological process (A), cellular component (B), and molecular function (C) in GO analysis and KEGG pathway (D) were obtained using the Enrichr database. A p-value < 0.05 was defined as a threshold for this analysis. The terms were sorted according to the combined score computed by the Enrichr database. ACE2: angiotensin-converting enzyme 2; TCGA: The Cancer Genome Atlas; COAD: Colon Adenocarcinoma; GO: Gene Ontology; KEGG: Kyoto Encyclopedia Of Genes And Genomes.