Fang Shaojun, Cheng Xianshuo, Shen Tao, Dong Jian, Li Yunfeng, Li Zhenhui, Tian Linghan, Zhang Yangwei, Pan Xueyan, Yin Zhengfeng, Yang Zhibin
Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital, Kunming 650118, China.
Department of Radiology, The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital, Kunming 650118, China.
Cancers (Basel). 2022 Oct 28;14(21):5300. doi: 10.3390/cancers14215300.
The role of CXCL8 and LSECtin in colon cancer liver metastasis and immune checkpoint inhibitors (ICIs) treatment effect were widely recognized. However, the regulatory role of CXCL8 on LSECtin is still unclear.
The expression of CXCL8 or LSECtin was analyzed by TCGA database, and verified by GES110225 and clinical samples. The relationship between the expression of CXCL8 or LSECtin and immune cells infiltration, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology (GO) items, stromal score, Estimation of STromal and Immune cells in MAlignant Tumours (ESTIMAT) immune score, tumor mutation burden (TMB), mismatch repair gene and immune checkpoints expression were analyzed by Spearman. The effects of CXCL8 on LSECtin expression, proliferation, and invasion ability were clarified by recombinant CXCL8 or CXCL8 interfering RNA.
In colon cancer, the expression of CXCL8 was higher, but LSECtin was lower than that in normal mucosa. The expression of CXCL8 or LSECtin was significantly positively correlated with immune cells infiltration, stromal score, ESTIMATE immune score, TMB, and immune checkpoints expression. The expression of LSECtin was closely related to the cytokine-cytokine receptor interaction pathway and response of chemokine function, such as CXCL8/CXCR1/2 pathway. There was a significant positive correlation between the expression of CXCL8 and LSECtin in colon cancer. CXCL8 up-regulated LSECtin through AKT signal and promoted the proliferation and invasion ability of colon cancer.
CXCL8 up-regulated LSECtin by activating AKT signal and correlated with the immune microenvironment modulation in colon cancer.
CXCL8和LSECtin在结肠癌肝转移及免疫检查点抑制剂（ICI）治疗效果中的作用已得到广泛认可。然而，CXCL8对LSECtin的调控作用仍不清楚。
通过TCGA数据库分析CXCL8或LSECtin的表达，并经GES110225和临床样本验证。采用Spearman分析CXCL8或LSECtin的表达与免疫细胞浸润、京都基因与基因组百科全书（KEGG）通路、基因本体论（GO）条目、基质评分、恶性肿瘤基质和免疫细胞估计（ESTIMAT）免疫评分、肿瘤突变负荷（TMB）、错配修复基因及免疫检查点表达之间的关系。通过重组CXCL8或CXCL8干扰RNA阐明CXCL8对LSECtin表达、增殖及侵袭能力的影响。
在结肠癌中，CXCL8的表达较高，但LSECtin的表达低于正常黏膜。CXCL8或LSECtin的表达与免疫细胞浸润、基质评分、ESTIMATE免疫评分、TMB及免疫检查点表达显著正相关。LSECtin的表达与细胞因子-细胞因子受体相互作用通路及趋化因子功能反应密切相关，如CXCL8/CXCR1/2通路。结肠癌中CXCL8与LSECtin的表达呈显著正相关。CXCL8通过AKT信号上调LSECtin，并促进结肠癌的增殖和侵袭能力。
CXCL8通过激活AKT信号上调LSECtin，并与结肠癌免疫微环境调节相关。
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