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.

中文翻译：

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LAGE3与透明细胞肾细胞癌微环境中的致瘤免疫浸润有关。

目的

透明细胞肾细胞癌（ccRCC）是全世界最常见的肾脏肿瘤类型。尚未广泛报道LAGE3（L抗原家族成员3）在ccRCC中的作用。在这项研究中，我们探讨了LAGE3在ccRCC中的临床意义和生物学功能。

方法

ccRCC患者的RNA-seq数据和相应的临床信息是从癌症基因组图谱（TCGA）和基因表达综合（GEO）数据库中提取的。使用ESTIMATE，quanTiseq和xCell算法来估计ccRCC微环境中的免疫渗透水平。

结果

我们发现，LAGE3的过表达与不良的临床病理因素相关，并且与多个ccRCC队列的不良预后相关。多变量分析表明，LAGE3是ccRCC患者的独立生存决定因素，而功能富集分析表明，LAGE3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，LAGE3与不同免疫细胞的免疫活性和浸润水平呈正相关。特别地，LAGE3表达对癌症-免疫周期的不同步骤具有积极影响。

结论

本研究结果表明，LAGE3可能是一个独立的生存预测因子，并且可能有助于开发新的ccRCC免疫治疗策略。