Ma Jiakang, Lin Xiaoyan, Wang Xueting, Min Qingqing, Wang Tonglian, Tang Chaozhi
Department of Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Ophthalmology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
Front Mol Biosci. 2021 Apr 27;8:644557. doi: 10.3389/fmolb.2021.644557. eCollection 2021.
Enhancer RNAs (eRNAs) participate in tumor growth and immune regulation through complex signaling pathways. However, the immune-related function of the eRNA-mRNA axis in lung adenocarcinoma (LUAD) is unclear. Data on the expression of eRNAs and mRNAs were downloaded from The Cancer Genome Atlas, GEO, and UCSC Xena, including LUAD, and pan-cancer clinical data and mutational information. Immune gene files were obtained from ImmLnc and ImmPort databases. Survival indices, including relapse-free and overall survival, were analyzed using the Kaplan-Meier and log-rank methods. The level of immune cell infiltration, degree of tumor hypoxia, and tumor cell stemness characteristics were quantified using the single-sample gene set enrichment analysis algorithm. The immune infiltration score and infiltration degree were evaluated using the ESTIMATE and CIBERSORT algorithms. The tumor mutation burden and microsatellite instability were examined using the Spearman test. The LUAD-associated immune-related LINC00987/A2M axis was down-regulated in most cancer types, indicating poor survival and cancer progression. Immune cell infiltration was closely related to abnormal expression of the LINC00987/A2M axis, linking its expression to a possible evaluation of sensitivity to checkpoint inhibitors and response to chemotherapy. Abnormal expression of the LINC00987/A2M axis was characterized by heterogeneity in the degree of tumor hypoxia and stemness characteristics. The abnormal distribution of immune cells in LUAD was also verified through pan-cancer analysis. Comprehensive bioinformatic analysis showed that the LINC00987/A2M axis is a functional and effective tumor suppressor and biomarker for assessing the immune microenvironment and prognostic and therapeutic evaluations of LUAD.
增强子RNA（eRNAs）通过复杂的信号通路参与肿瘤生长和免疫调节。然而，eRNA-信使核糖核酸（mRNA）轴在肺腺癌（LUAD）中的免疫相关功能尚不清楚。从癌症基因组图谱（The Cancer Genome Atlas）、基因表达综合数据库（GEO）和加州大学圣克鲁兹分校（UCSC）Xena数据库下载了包括LUAD在内的eRNAs和mRNAs的表达数据，以及泛癌临床数据和突变信息。从ImmLnc和ImmPort数据库获取免疫基因文件。使用Kaplan-Meier法和对数秩检验分析无复发生存率和总生存率等生存指标。使用单样本基因集富集分析算法量化免疫细胞浸润水平、肿瘤缺氧程度和肿瘤细胞干性特征。使用ESTIMATE和CIBERSORT算法评估免疫浸润评分和浸润程度。使用Spearman检验检测肿瘤突变负荷和微卫星不稳定性。在大多数癌症类型中，LUAD相关的免疫相关长链非编码RNA 00987（LINC00987）/α2-巨球蛋白（A2M）轴下调，表明生存率低和癌症进展。免疫细胞浸润与LINC00987/A2M轴的异常表达密切相关，将其表达与对检查点抑制剂的敏感性评估和化疗反应联系起来。LINC00987/A2M轴的异常表达以肿瘤缺氧程度和干性特征的异质性为特征。通过泛癌分析也验证了LUAD中免疫细胞的异常分布。综合生物信息学分析表明，LINC00987/A2M轴是一种功能性且有效的肿瘤抑制因子和生物标志物，可用于评估LUAD的免疫微环境以及预后和治疗评估。
