Luan Mingyuan, Tian Xue, Zhang Dexiang, Sun Xiaoning, Jiang Minglu, Duan Yunbo, Sun Changgang, Si Hongzong
Organ Transplantation Center, the Affiliated Hospital of Qingdao University, Qingdao, China.
School of Basic Medicine, Qingdao University Medical College, Qingdao, China.
Transl Cancer Res. 2021 Feb;10(2):724-737. doi: 10.21037/tcr-20-2714.
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.
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.
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.
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.
中性粒细胞在肝细胞癌（HCC）的发生和发展中起关键作用；然而，中性粒细胞募集的潜在机制尚未完全明确。因此，我们旨在探索癌症微环境中与中性粒细胞募集相关的潜在基因或途径。
我们下载了TCGA HCC基因表达谱、HCC患者中22种不同免疫细胞的丰度以及患者生存信息。我们使用Kaplan-Meier生存分析来确定中性粒细胞是否与生存相关。接下来，我们筛选了中性粒细胞水平高和低的患者之间的差异表达基因（DEG）。然后，我们在DEG范围内鉴定转录因子及其靶标。然后，我们对靶标进行富集分析和基因集变异分析（GSVA）。最后，我们通过计算相关评分来探索靶标的潜在机制。
我们的生存分析结果表明，中性粒细胞与患者生存显著相关。共筛选出736个DEG。接下来，我们从736个DEG中鉴定出转录因子大E26转化特异性（ETS）同源因子（EHF）和702个EHF靶标。在这些靶标中，FGD6表达水平与EHF表达水平的相关性最高。对FGD6的富集和GSVA分析表明，GO:0043547水平对GTPase活性具有正调控作用，并且GO:0007010细胞骨架组织在中性粒细胞计数高和低之间存在显著差异。通过计算FGD6与GO:0043547和GO:0007010中的基因之间的相关性，我们鉴定出RIC8B和SIPA1L3。
这些发现表明转录因子EHF可通过介导FGD6的转录来影响中性粒细胞的募集。需要进一步研究以阐明EHF及其靶标FGD6。
