Nie Yuan, Jiang Mei-Chun, Liu Cong, Liu Qi, Zhu Xuan
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Front Oncol. 2021 Mar 31;11:637023. doi: 10.3389/fonc.2021.637023. eCollection 2021.
Tumor microenvironment (TME) plays a crucial role in the initiation and progression of Hepatocellular Carcinoma (HCC), especially immune infiltrates. However, there is still a challenge in understanding the modulation of the immune and stromal components in TME, especially TME related genes.
The proportion of tumor-infiltrating immune cells (TICs) and the immune and stromal scores in 374 HCC patients from The Cancer Genome Atlas (TCGA) database were determined using CIBERSORT and ESTIMATE computational methods. The final screened genes were confirmed by the PPI network and univariate Cox regression of the differentially expressed genes based on different immune or stromal scores. The correlation between the expression levels of the final gene interactions and the clinical characteristics was based on TCGA database and local hospital data. Gene set enrichment analysis (GSEA) and the effect of CXCL5 expression on TICs were conducted.
There were correlations between the expression of CXCL5 and survival of HCC patients and TMN classification both in TCGA database and local hospital data. The immune-related activities were enriched in the high-expression group; however, the metabolic pathways were enriched in the low-expression group. The result of CIBERSORT analyzing had indicated that CXCL5 expression were correlated with the proportion of NK cells activated, macrophages M0, Mast cells resting, Neutrophils.
CXCL5 was a potential prognostic marker for HCC and provides clues regarding immune infiltrates, which offers extra insight for therapeutics of HCC, however, more independent cohorts and functional experiments of CXCL5 are warranted.
肿瘤微环境(TME)在肝细胞癌(HCC)的发生和发展中起着关键作用,尤其是免疫浸润。然而,在理解TME中免疫和基质成分的调节,特别是与TME相关的基因方面,仍然存在挑战。
使用CIBERSORT和ESTIMATE计算方法确定来自癌症基因组图谱(TCGA)数据库的374例HCC患者的肿瘤浸润免疫细胞(TICs)比例以及免疫和基质评分。通过蛋白质-蛋白质相互作用(PPI)网络和基于不同免疫或基质评分的差异表达基因的单变量Cox回归来确认最终筛选的基因。最终基因相互作用的表达水平与临床特征之间的相关性基于TCGA数据库和当地医院的数据。进行基因集富集分析(GSEA)以及CXCL5表达对TICs的影响。
在TCGA数据库和当地医院数据中,CXCL5的表达与HCC患者的生存率和TMN分类之间均存在相关性。免疫相关活动在高表达组中富集;然而,代谢途径在低表达组中富集。CIBERSORT分析结果表明,CXCL5表达与活化的自然杀伤细胞、M0巨噬细胞、静止肥大细胞、中性粒细胞的比例相关。
CXCL5是HCC的潜在预后标志物,并为免疫浸润提供线索,这为HCC的治疗提供了额外的见解,然而,需要更多关于CXCL5的独立队列研究和功能实验。