Identifying the potential regulators of neutrophils recruitment in hepatocellular carcinoma using bioinformatics method

BACKGROUND: Neutrophils play a crucial role in the development and progression of hepatocellular carcinoma (HCC); however, the mechanism underlying neutrophil recruitment is not fully understood. Therefore, we aimed to explore the potential genes or pathways related to neutrophil recruitment in the cancer microenvironment. METHODS: We downloaded TCGA HCC gene expression profiles, the abundance of 22 different immune cells in HCC patients, and patient survival information. We used Kaplan-Meier survival analysis to determine if neutrophils were related to survival. Next, we screened different expression genes (DEGs) between patients with high and low level of neutrophils. We then identified the transcription factor and its targets in the fence of DEGs. Then, we carried out enrichment analysis and gene set variation analysis (GSVA) for targets. Finally, we explored the potential mechanism of targets via calculating correlation scores. RESULTS: Our survival analysis results showed that neutrophils were significantly associated with patient survival. A total of 736 DEGs were screened. Next, we identified transcription factor larger E26 transformation-specific (ETS) homologous factor (EHF) and 702 targets of EHF from 736 DEGs. Among these targets, the level of FGD6 expression had the highest correlation with the level of EHF expression. Enrichment and GSVA analysis for FGD6 showed that the level of GO:0043547 had a positive regulatory effect on GTPase activity and the GO:0007010 cytoskeleton organization was significantly difference between the high and low neutrophils counts. By calculating the correlation between FGD6 and genes in GO:0043547 and GO:0007010, we identified RIC8B and SIPA1L3. CONCLUSIONS: These findings demonstrated that transcription factor EHF can influence recruitment of neutrophils by mediating the transcription of FGD6. Further investigations are needed to shed new light on EHF and its target FGD6.