Abstract
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.
Highlights
According to the latest data from global cancer statistics, lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death around the whole world (Bray et al, 2018)
To evaluate the transcription level of Aldolase A (ALDOA) in multiple lung adenocarcinoma studies, we performed an analysis on Oncomine
To further evaluate the relationship between ALDOA and tumor-infiltrating immune cells, we explored the correlation between ALDOA expression and immunological markers in lung adenocarcinoma using the Tumor Immune Estimation Resource (TIMER) database
Summary
According to the latest data from global cancer statistics, lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death around the whole world (Bray et al, 2018). ALDOA has been reported to be involved in gluconeogenesis and glycolysis (Zeng et al, 2016) Based on both gluconeogenesis and glycolysis can provide energy for tumor proliferation, accumulating evidence has indicated that ALDOA plays an important role in the pathological progress of several cancers. Concerning non-small cell lung cancer, Fu et al reported that ALDOA can activate the EGFR/MAPK pathway to promote cyclin D1 expression, enhance proliferation and G1/G transition, and facilitate aerobic glycolysis (Fu et al, 2018). These findings indicate that ALDOA plays an important role in tumor progression
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