DataSheet1_Prognostic Implications and Immune Infiltration Analysis of ALDOA in Lung Adenocarcinoma.CSV

Background: aldolase A (ALDOA) has been reported to be involved in kinds of cancers. However, the role of ALDOA in lung adenocarcinoma has not been fully elucidated. In this study, we explored the prognostic value and correlation with immune infiltration of ALDOA in lung adenocarcinoma.
Methods: The expression of ALDOA was analyzed with the Oncomine database, the Cancer Genome Atlas (TCGA), and the Human Protein Atlas (HPA). Mann-Whitney U test was performed to examine the relationship between clinicopathological characteristics and ALDOA expression. The receiver operating characteristic (ROC) curve and Kaplan-Meier method were conducted to describe the diagnostic and prognostic importance of ALDOA. The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape were used to construct PPI networks and identify hub genes. Functional annotations and immune infiltration were conducted.
Results: The mRNA and protein expression of ALDOA were higher in lung adenocarcinoma than those in normal tissues. The overexpression of ALDOA was significantly correlated with the high T stage, N stage, M stage, and TNM stage. Kaplan-Meier showed that high expression of ALDOA was correlated with short overall survival (38.9 vs 72.5 months, p < 0.001). Multivariate analysis revealed that ALDOA (HR 1.435, 95%CI, 1.013–2.032, p = 0.042) was an independent poor prognostic factor for overall survival. Functional enrichment analysis showed that positively co-expressed genes of ALDOA were involved in the biological progress of mitochondrial translation, mitochondrial translational elongation, and negative regulation of cell cycle progression. KEGG pathway analysis showed enrichment function in carbon metabolism, the HIF-1 signaling pathway, and glycolysis/gluconeogenesis. The “SCNA” module analysis indicated that the copy number alterations of ALDOA were correlated with three immune cell infiltration levels, including B cells, CD8+ T cells, and CD4+ T cells. The “Gene” module analysis indicated that ALDOA gene expression was negatively correlated with infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, and macrophages.
Conclusion: Our study suggested that upregulated ALDOA was significantly correlated with tumor progression, poor survival, and immune infiltrations in lung adenocarcinoma. These results suggest that ALDOA is a potential prognostic biomarker and therapeutic target in lung adenocarcinoma.

背景：已有研究显示醛缩酶A（aldolase A, ALDOA）参与多种癌症的发生发展。然而，ALDOA在肺腺癌中的作用尚未完全阐明。本研究旨在探讨ALDOA在肺腺癌中的预后价值及其与免疫浸润的相关性。
方法：本研究通过Oncomine数据库、癌症基因组图谱（Cancer Genome Atlas, TCGA）以及人类蛋白质图谱（Human Protein Atlas, HPA）分析ALDOA的表达水平。采用曼-惠特尼U检验（Mann-Whitney U test）分析临床病理特征与ALDOA表达的相关性。通过受试者工作特征（receiver operating characteristic, ROC）曲线及Kaplan-Meier法评估ALDOA的诊断与预后价值。利用STRING（Search Tool for the Retrieval of Interacting Genes）数据库与Cytoscape软件构建蛋白质相互作用（protein-protein interaction, PPI）网络并筛选核心基因（hub genes）。此外，还进行了功能注释与免疫浸润分析。
结果：肺腺癌组织中ALDOA的mRNA与蛋白质表达水平均显著高于正常组织。ALDOA过表达与较高的T分期、N分期、M分期及TNM分期显著相关。Kaplan-Meier生存分析显示，ALDOA高表达患者的总生存期较短（38.9个月 vs 72.5个月，p < 0.001）。多因素分析表明，ALDOA（风险比HR=1.435，95%置信区间CI：1.013~2.032，p=0.042）是总生存期的独立不良预后因素。功能富集分析显示，ALDOA的正相关共表达基因参与线粒体翻译、线粒体翻译延伸以及细胞周期进程负调控等生物学过程。KEGG通路富集分析显示，ALDOA相关基因主要富集于碳代谢、缺氧诱导因子1（hypoxia-inducible factor 1, HIF-1）信号通路以及糖酵解/糖异生过程。"SCNA"模块分析显示，ALDOA的拷贝数变异与B细胞、CD8+T细胞、CD4+T细胞这三种免疫细胞的浸润水平显著相关。"Gene"模块分析显示，ALDOA基因表达与B细胞、CD8+T细胞、CD4+T细胞及巨噬细胞的浸润水平呈负相关。
结论：本研究表明，肺腺癌中ALDOA表达上调与肿瘤进展、不良预后及免疫浸润显著相关。上述结果提示，ALDOA有望成为肺腺癌潜在的预后生物标志物与治疗靶点。