溶质载体转运蛋白家族11成员1在结直肠癌中的表达及其与免疫微环境的关系
Expression of solute carrier family 11 member 1 in colorectal cancer and its relationship with immune microenvironment
摘要目的:探讨溶质载体转运蛋白家族11成员1(SLC11A1)在结直肠癌中的表达及其与结直肠癌免疫微环境的关系。方法:从癌症基因组图谱数据库(TCGA)下载结直肠癌及癌旁正常组织的基因表达及临床数据,分析SLC11A1其在结直肠癌样本中的表达水平及与患者临床病理指标及预后的关系,采用配对样本 t检验分析其表达差异, χ2检验分析其与相关临床病理指标的关系,Kaplan-Meier法分析其与预后的关系。通过基因集富集分析(GSEA)探讨SLC11A1参与结直肠癌发生发展的可能机制,通过单样本基因集富集分析(ssGSEA)及Spearman相关性分析探索SLC11A1表达与结直肠癌不同亚型免疫细胞浸润的相关性。 结果:与正常组织比较,结直肠癌中SLC11A1高表达(1.207±0.694比0.276±0.166, t=8.281, P<0.01)。SLC11A1的表达水平与肿瘤浸润深度( χ2=5.38, P<0.05)呈明显相关。SLC11A1高表达与患者不良预后有关( χ2=6.43, P<0.05)。多因素分析结果表明SLC11A1表达[风险比( HR)=1.126,95%可信区间( CI):1.001~1.266, P<0.05]为影响结直肠癌预后的独立因素。基因集富集分析结果表明SLC11A1可能通过Toll样受体信号通路、自然杀伤细胞介导的细胞毒性以及细胞因子/细胞因子受体相互作用等参与结直肠癌发生发展。ssGSEA分析结果表明SLC11A1表达与DC细胞( r=0.526, P<0.01)、巨噬细胞( r=0.796, P<0.01)、中性粒细胞( r=0.679, P<0.01)等多种免疫细胞浸润相关。 结论:SLC11A1在结直肠癌中显著高表达,且与结直肠癌不良预后相关,可能作为结直肠癌的潜在预后标志物及治疗靶点。
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abstractsObjective:To investigate the expression and clinical significance of solute carrier family 11 member 1 (SLC11A1) in colorectal cancer and its relationship with colorectal cancer immune microenvironment.Methods:The gene expression and clinical data of colorectal cancer and adjacent normal tissues were downloaded from the Cancer Genome Atlas Database (TCGA). The expression information of SLC11A1 was extracted to analyze the expression level of SLC11A1 in colorectal cancer samples and its relationship with clinicopathological indexes and prognosis. The expression difference was analyzed by paired sample t-test. Its relationship with relevant clinicopathological indexes was analyzed by chi square test. Kaplan Meier method was used to analyze its relationship with prognosis. The possible mechanism of SLC11A1 involved in the occurrence and development of colorectal cancer was detected by gene set enrichment analysis (GSEA). The correlation between SLC11A1 expression and immune cell infiltration of different subtypes in colorectal cancer was analyzed by single sample gene set enrichment analysis (ssGSEA) and Spearman method. Results:Compared with normal tissues, SLC11A1 was up-regulated in colorectal cancer (1.207±0.694 vs. 0.276±0.166, t=8.281, P<0.01). The expression of SLC11A1 was correlated with the depth of tumor invasion ( χ2=5.38, P<0.05). The high expression of SLC11A1 was related to the adverse prognosis of patients ( χ2=6.43, P<0.05). Multivariate analysis showed that the expression of SLC11A1 [hazard ratio ( HR)=1.126, 95% confidence interval ( CI): 1.001-1.266, P<0.05] was an independent factor affecting the prognosis of colorectal cancer. SLC11A1 may participate in the development of colorectal cancer by toll like receptor signaling pathway, natural killer cells-mediated cytotoxicity and cytokine-cytokine receptor interaction, etc. The enrichment analysis of GO and KEGG showed that these genes were mainly related to extracellular matrix components. SsGSEA analysis showed that SLC11A1 expression was related to DC cells ( r=0.526, P<0.01), macrophages ( r=0.796, P<0.01), neutrophils ( r=0.679, P<0.01), etc. Conclusion:SLC11A1 is up-regulated in colorectal cancer, which is associated with poor prognosis of colorectal cancer. It may be a potential prognostic marker and therapeutic target of colorectal cancer.
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