Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, #1 Nan Bai Xiang Street, Wenzhou 325006, China.
Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, #1 Nan Bai Xiang Street, Wenzhou, China.
Int Immunopharmacol. 2020 Oct;87:106793. doi: 10.1016/j.intimp.2020.106793. Epub 2020 Jul 17.
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.
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.
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.
The present findings disclose that LAGE3 could be an independent survival predictor, and might contribute to developing novel ccRCC immunological treatment strategies.
透明细胞肾细胞癌(ccRCC)是全球最常见的肾肿瘤类型。LAGE3(L 抗原家族成员 3)在 ccRCC 中的作用尚未得到广泛报道。在本研究中,我们探讨了 LAGE3 在 ccRCC 中的临床意义和生物学功能。
从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中提取了 ccRCC 患者的 RNA-seq 数据及其相应的临床信息。ESTIMATE、quanTiseq 和 xCell 算法用于估计 ccRCC 微环境中的免疫浸润水平。
我们发现 LAGE3 的过表达与不良的临床病理因素相关,并与多个 ccRCC 队列的不良预后相关。多变量分析表明,LAGE3 是 ccRCC 患者独立的生存决定因素,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。进一步的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。特别是,LAGE3 表达对癌症-免疫循环的不同步骤有积极影响。
本研究结果表明,LAGE3 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。