LAGE3 correlates with tumorigenic immune infiltrates in the clear cell renal cell carcinoma microenvironment
LAGE3 correlates with tumorigenic immune infiltrates in the clear cell renal cell carcinoma microenvironment
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LAGE3 与透明细胞肾细胞癌微环境中致瘤性免疫浸润相关
DOI：
10.1016/j.intimp.2020.106793
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发表时间：
2020-10-01
影响因子：
5.6
通讯作者：
Ye, Zhiqiang
中科院分区：
文献类型：
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作者：
Dong, Xubin;Gu, Dian-Na;Ye, Zhiqiang
目的：肾透明细胞癌（Clear cell renal cell carcinoma，ccRCC）是世界上最常见的肾脏肿瘤。LAGE 3（L抗原家族成员3）在ccRCC中的作用尚未得到广泛报道。方法：从TCGA和GEO数据库中提取ccRCC患者的RNA-seq数据和相应的临床信息，并对LAGE 3基因在ccRCC中的表达进行分析。ESTIMATE、quanTiseq和xCell算法用于估计ccRCC微环境中的免疫浸润水平。结果：我们发现LAGE 3的过表达与不良临床病理因素相关，并且与多个ccRCC队列中的不良预后相关。多变量分析表明LAGE 3是ccRCC患者的独立生存决定因素，而功能富集分析表明LAGE 3可能调节体液免疫反应、免疫球蛋白复合物和受体-配体活性。此外，基于不同算法的肿瘤微环境分析表明LAGE 3与不同免疫细胞的免疫活性和浸润水平正相关。特别是，LAGE 3的表达对癌症免疫cycle.Conclusion的不同步骤产生了积极的影响：目前的研究结果表明，LAGE 3可能是一个独立的生存预测因子，并可能有助于开发新的ccRCC免疫治疗策略。
Objective: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor worldwide. The role of LAGE3 (L Antigen Family Member 3) in ccRCC has not been widely reported. In this study, we explored the clinical significances and biological functions of LAGE3 in ccRCC.Methods: The RNA-seq data and the corresponding clinical information of the patients with ccRCC were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ESTIMATE, quanTiseq, and xCell algorithms were used to estimate the immune infiltration levels in the ccRCC microenvironment.Results: We found that overexpression of LAGE3 was associated with adverse clinical-pathological factors, and correlated with poor prognosis in multiple ccRCC cohorts. Multivariate analysis indicated that LAGE3 was an independent survival determinant in patients with ccRCC, whereas functional enrichment analysis suggested that LAGE3 may regulate humoral immune response, immunoglobulin complex, and receptor-ligand activity. Further, tumor microenvironment analysis based on different algorithms indicated LAGE3 was positively associated with the immune activity and infiltrating levels of different immune cells. Particularly, LAGE3 expression had a positive impact on different steps of the cancer-immunity cycle.Conclusion: The present findings disclose that LAGE3 could be an independent survival predictor, and might contribute to developing novel ccRCC immunological treatment strategies.