目的：探讨表皮生长因子蛛毒素受体7 穿膜结构域蛋白1（ELTD1）在肾透明细胞癌（ccRCC）组织中的表达、甲基化水 平及其与患者临床病理特征和预后的相关性。方法：通过公共数据库分析ccRCC 组织中ELTD1 表达和甲基化的差异水平，探讨 ELTD1 表达水平与患者临床病理特征和预后的相关性。通过TIMER2.0 数据库评估ccRCC 免疫细胞浸润，筛选ELTD1 相关免疫 检查点基因，进行GO 功能和KEGG 通路富集分析，通过基因共表达分析、筛选与ELTD1 相关的基因。结果：与癌旁组织比较，ELTD1 在ccRCC 组织中呈高表达（P<0.05）。TCGA-KIRC 队列中，ELTD1 的甲基化水平与其表达呈负相关（R=-0.37，P<0.01）。 ELTD1 转录表达在ccRCC 患者年龄、T 分期、M 分期、临床分期及病理分级组间存在显著差异（均P<0.01），且高表达ELTD1 与较 长的OS 和PFS 密切相关（HR=0.55、0.63，均P<0.01），ELTD1 高表达是ccRCC 的独立保护因素。ELTD1 表达与B 细胞、CD4+ T 细 胞、CD8+ T 细胞、巨噬细胞和嗜中性粒细胞的免疫浸润呈显著负相关（R=-0.16、-0.27、-0.25、-0.31、-0.27，均P<0.01）。GO 功能和 KEGG 通路富集分析结果显示，血管生成及肿瘤相关信号通路在ELTD1 高表达表型中显著富集（均P<0.01）。ELTD1 共表达基因 的生存分析提示，其肿瘤抑制作用与共表达网络有关。结论：ELTD1 在ccRCC 组织中高表达和低甲基化是患者预后良好的指标，且与免疫浸润相关。

Objective: To investigate the expression and methylation level of epidermal growth factor, latrophilin and seven transmembrane domain-containing 1 (ELTD1) in clear cell renal cell carcinoma (ccRCC) and their correlation with the clinicopathological features and prognosis of patients. Methods: The differential expression and methylation of ELTD1 gene were analyzed with open databases to discuss the correlation between the ELTD1 expression and the clinicopathological characteristics and prognosis of patients. TIMER 2.0 database was adopted to analyze the tumor immune cell infiltration of ccRCC and screen out ELTD1-related immune checkpoint genes. GO function enrichment and KEGG pathway enrichment analysis were also performed. The genes closely related to ELTD1 were identified through gene co-expression analysis. Results: ELTD1 was significantly upregulated in ccRCC (P<0.05), whose expression is negatively correlated with its methylation in TCGA-KIRC (R=-0.37, P<0.01). ELTD1 transcription expression was significantly correlated with age, T stage, M stage and grade (all P<0.01). Higher expression of ELTD1 was closely associated with overall survival (OS) (HR=0.55, P<0.01) and progression-free survival (PFS) (HR=0.63, P<0.01). Upregulation of ELTD1 expression was an independent protective factor in ccRCC. ELTD1 expression was significantly correlated with immune infiltrating of B cells (R=-0.16, P<0.01), CD4+ T cells (R=-0.27, P<0.01), CD8+ T cells (R=-0.25, P<0.01), macrophages (R=-0.31, P<0.01) and neutrophils (R=-0.27, P<0.001), and diverse immune checkpoint genes (all P<0.01). GO function and KEGG pathway enrichment analysis showed that vascular process and tumor-related signaling pathways were enriched in the ELTD1 high expression phenotypes (all P<0.01). Gene co-expression analysis showed that the effect of tumor inhibition was related to the co-expression network. Conclusion: Upregulation of ELTD1 expression and lower methylation level of ELTD1 in ccRCC are indicators of better prognosis and are related to tumor immune infiltration.

国家自然科学基金资助项目（No.82070814）