AUTHOR=Lu Guojun , Shi Wen , Zhang Yu 

TITLE=Prognostic Implications and Immune Infiltration Analysis of ALDOA in Lung Adenocarcinoma

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.721021

DOI=10.3389/fgene.2021.721021

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> aldolase A (<italic>ALDOA</italic>) has been reported to be involved in kinds of cancers. However, the role of <italic>ALDOA</italic> in lung adenocarcinoma has not been fully elucidated. In this study, we explored the prognostic value and correlation with immune infiltration of <italic>ALDOA</italic> in lung adenocarcinoma.</p><p><bold>Methods:</bold> The expression of <italic>ALDOA</italic> was analyzed with the Oncomine database, the Cancer Genome Atlas (TCGA), and the Human Protein Atlas (HPA). Mann-Whitney <italic>U</italic> test was performed to examine the relationship between clinicopathological characteristics and <italic>ALDOA</italic> expression. The receiver operating characteristic (ROC) curve and Kaplan-Meier method were conducted to describe the diagnostic and prognostic importance of <italic>ALDOA</italic>. 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.</p><p><bold>Results:</bold> The mRNA and protein expression of <italic>ALDOA</italic> were higher in lung adenocarcinoma than those in normal tissues. The overexpression of <italic>ALDOA</italic> was significantly correlated with the high T stage, N stage, M stage, and TNM stage. Kaplan-Meier showed that high expression of <italic>ALDOA</italic> was correlated with short overall survival (38.9 vs 72.5 months, <italic>p</italic> &lt; 0.001). Multivariate analysis revealed that <italic>ALDOA</italic> (HR 1.435, 95%CI, 1.013–2.032, <italic>p</italic> = 0.042) was an independent poor prognostic factor for overall survival. Functional enrichment analysis showed that positively co-expressed genes of <italic>ALDOA</italic> 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 <italic>ALDOA</italic> were correlated with three immune cell infiltration levels, including B cells, CD8<sup>+</sup> T cells, and CD4<sup>+</sup> T cells. The “Gene” module analysis indicated that <italic>ALDOA</italic> gene expression was negatively correlated with infiltrating levels of B cells, CD8<sup>+</sup> T cells, CD4<sup>+</sup> T cells, and macrophages.</p><p><bold>Conclusion:</bold> Our study suggested that upregulated <italic>ALDOA</italic> was significantly correlated with tumor progression, poor survival, and immune infiltrations in lung adenocarcinoma. These results suggest that <italic>ALDOA</italic> is a potential prognostic biomarker and therapeutic target in lung adenocarcinoma.</p>