肿瘤微环境趋化因子通过与细胞因子受体互作参与HCC诱导的炎症反应

Chemokines are involved in the HCC induced- inflammatory response via interaction with cytokine receptor in tumor microenvironment

目的探讨肿瘤微环境(TM)中趋化因子参与肝细胞癌(HCC)引起的炎症反应的可能机制。方法提取肿瘤组织(TM组)和癌旁组织(对照组)总RNA并通过RNA-seq和生物信息学手段分析趋化因子相关差异表达基因的功能及其编码蛋白的互作情况,并以RT-qPCR验证实验结果。结果TM中共有43个趋化因子相关差异表达基因,它们被富集到2个KEGG信号通路、5个生物学过程和2个细胞组分,其中大量趋化因子相关基因参与炎症反应、免疫反应、趋化性、细胞对IL-1的反应和细胞对肿瘤坏死因子的反应过程。尤其值得一提的是,涉及趋化性的7个基因(ACKR3、CCL20、CCL3、CCL5、CCR4、CCR6、PTGDR2)中,有6个参与细胞因子-细胞因子受体信号通路、5个参与免疫反应、4个参与炎症反应;涉及细胞因子-细胞因子受体信号通路的134个基因中有7个参与炎症反应。结论TM中趋化因子通过与细胞因子受体互作的方式参与HCC诱导的炎症反应。

Objective To investigate the possible mechanism of chemokines which are involved in hepatocellular carcinoma(HCC)-induced inflammatory response in tumor microenvironment(TM).Methods Total RNA was extracted from tumor tissues(TM group)and paracancerous tissues(control group)and the function of chemokine-related differentially expressed genes and the interaction of their encoded proteins were analyzed by RNA-seq and bioinformatics ways.RT-qPCR was used to verify the experiment results.Results There were 43 chemokine-related differentially expressed genes in the TM,they were enriched into 2 KEGG signal pathways,5 biological processes and 2 cellular components.Most of chemokine-related genes were involved in processes such as inflammatory response,immune response,chemotaxis,cellular response to interleukin-1 and cellular response to tumor necrosis factor.It was worth mentioning that 6 out of the 7 genes involved in chemotaxis(ACKR3,CCL20,CCL3,CCL5,CCR4,CCR6,PTGDR2)were participated in the signaling pathway of cytokine-cytokine receptor interaction,5 were involved in the immune response,4 were involved in the inflammatory response.Seven out of the 134 genes involved in the signaling pathway of cytokine-cytokine receptor interaction were involved in the inflammatory response.Conclusion Chemokines in the TM participate in the HCC-induced inflammatory responses via interacting with cytokine receptors.