High expression of aldolase A is associated with tumor progression and poor prognosis in hepatocellular carcinoma

Tang, Yan; Feng, Ke; Hu, Chang-Lu; Li, Suyi

doi:10.21037/jgo-20-534

Cited by 21 publications

(18 citation statements)

References 30 publications

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“…Additionally, high FBP1 correlates with lung squamous cell carcinoma, and low FBP1 correlates with uterine corpus endometrial cancer (p=0.00052). Similar trends were observed in LUAD and LIHC with respect to ALDOA expression and overall survival, first progression, and postp-rogression survival ( Supplementary Figures 2 , 3 ), which is consistent with overexpression of ALDOA being associated with poor prognosis in surgical specimens [ 7 , 15 , 17 , 43 ]. We previously observed that ALDOA expression correlated more strongly with poor prognosis in lung cancer [ 9 , 10 , 18 ].…”

Section: Discussionsupporting

confidence: 79%

The role of fructose 1,6-bisphosphate-mediated glycolysis/gluconeogenesis genes in cancer prognosis

Chan

Chang

2022

Aging

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Metabolic reprogramming and elevated glycolysis levels are associated with tumor progression. However, despite cancer cells selectively inhibiting or expressing certain metabolic enzymes, it is unclear whether differences in gene profiles influence patient outcomes. Therefore, identifying the differences in enzyme action may facilitate discovery of gene ontology variations to characterize tumors. Fructose-1,6-bisphosphate (F-1,6-BP) is an important intermediate in glucose metabolism, particularly in cancer. Gluconeogenesis and glycolysis require fructose-1,6-bisphosphonates 1 (FBP1) and fructose-bisphosphate aldolase A (ALDOA), which participate in F-1,6-BP conversion. Increased expression of ALDOA and decreased expression of FBP1 are associated with the progression of various forms of cancer in humans. However, the exact molecular mechanism by which ALDOA and FBP1 are involved in the switching of F-1,6-BP is not yet known. As a result of their pancancer pattern, the relationship between ALDOA and FBP1 in patient prognosis is reversed, particularly in lung adenocarcinoma (LUAD) and liver hepatocellular carcinoma (LIHC). Using The Cancer Genome Atlas (TCGA), we observed that FBP1 expression was low in patients with LUAD and LIHC tumors, which was distinct from ALDOA. A similar trend was observed in the analysis of Cancer Cell Line Encyclopedia (CCLE) datasets. By dissecting downstream networks and possible upstream regulators, using ALDOA and FBP1 as the core, we identified common signatures and interaction events regulated by ALDOA and FBP1. Notably, the identified effectors dominated by ALDOA or FBP1 were distributed in opposite patterns and can be considered independent prognostic indicators for patients with LUAD and LIHC. Therefore, uncovering the effectors between ALDOA and FBP1 will lead to novel therapeutic strategies for cancer patients.

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Section: Discussionsupporting

confidence: 79%

The role of fructose 1,6-bisphosphate-mediated glycolysis/gluconeogenesis genes in cancer prognosis

Chan

Chang

2022

Aging

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“…Interestingly, the proteomic analysis revealed differential expression of glycolysis pathway, being lactate dehydrogenase A (LDHA), lactate dehydrogenase B (LDHB) and fructose-biphosphate aldolase A (ALDOA), the identified downregulated glycolytic enzymes by ( IA ) treatment. ALDOA is a key glycolytic enzyme, the high expression of which has been associated to tumor progression and poor prognosis in hepatocellular carcinoma [ 33 ]. Glycolytic enzymes play a physiological role that is not limited to catalytic function and can participate as regulators of cellular processes, such as actin filaments organization, p53 signaling, and cell cycle progression, considered as necessary cellular events for survival and proliferation of cancer cells.…”

Section: Resultsmentioning

confidence: 99%

“…In order to visualize the different clusters involved in pro-apoptotic activity of IA , we performed a Protein–Protein Interaction Analysis (PPI) of differentially expressed proteins ( Figure 5 ) and the results obtained suggest that the possible action mechanism may be the apoptosis activation, where glycolytic enzymes ALDOA, LDHA and LDHB were biologically connected to pro-apoptotic proteins as BAX and BID, as well to the glutathione transferases MGST1 and GSTK1 [ 33 , 34 ].…”

Section: Resultsmentioning

confidence: 99%

Incomptine A Induces Apoptosis, ROS Production and a Differential Protein Expression on Non-Hodgkin’s Lymphoma Cells

Pina-Jiménez

Calzada

Bautista

et al. 2021

IJMS

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Sesquiterpene lactones are of pharmaceutical interest due their cytotoxic and antitumor properties, which are commonly found within plants of several genera from the Asteraceae family such as the Decachaeta genus. From Decachaeta incompta four heliangolide, namely incomptines A-D have been isolated. In this study, cytotoxic properties of incomptine A (IA) were evaluated on four lymphoma cancer cell lines: U-937, Farage, SU-DHL-2, and REC-1. The type of cell death induced by IA and its effects on U-937 cells were analyzed based on its capability to induce apoptosis and produce reactive oxygen species (ROS) through flow cytometry with 4′,6-diamidino-2-phenylindole staining, dual annexin V/DAPI staining, and dichlorofluorescein 2′,7′-diacetate, respectively. A differential protein expression analysis study was carried out by isobaric tags for relative and absolute quantitation (iTRAQ) through UPLC-MS/MS. Results reveal that IA exhibited cytotoxic activity against the cell line U-937 (CC50 of 0.12 ± 0.02 μM) and the incubation of these cells in presence of IA significantly increased apoptotic population and intracellular ROS levels. In the proteomic approach 1548 proteins were differentially expressed, out of which 587 exhibited a fold-change ≥ 1.5 and 961 a fold-change ≤ 0.67. Most of these differentially regulated proteins are involved in apoptosis, oxidative stress, glycolytic metabolism, or cytoskeleton structuration.

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“…Many studies about the dysregulation of the ALDOA gene have emerged in recent years, including colorectal cancer (Dai et al, 2018), gastric cancer (Jiang et al, 2018), and renal cell carcinoma (Huang et al, 2018). Previous bioinformatics results also indicated that ALDOA expression was correlated with prognosis in bladder cancer (Li et al, 2019), hepatocellular cancer (Tang et al, 2021). In lung cancer, overexpression of ALDOA is reported to promote lung cancer cell proliferation and metastasis (Chang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…In the current study, ROC curve analysis suggested that ALDOA can act as a prospective non-invasive diagnostic biomarker to differentiate lung adenocarcinoma tissues from adjacent normal tissues. Previous studies reported that upregulation of ALDOA is correlated with poor prognosis in colorectal cancer ( Dai et al, 2018 ), gastric cancer ( Jiang et al, 2018 ), and hepatocellular carcinoma ( Tang et al, 2021 ). Our data on survival analysis with GEPIA2 and the Kaplan Meier plotter indicated that lung adenocarcinoma patients with high ALDOA expression or genetic alteration have a poor overall survival prognosis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Implications and Immune Infiltration Analysis of ALDOA in Lung Adenocarcinoma

Shi

2021

Front. Genet.

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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.

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High expression of aldolase A is associated with tumor progression and poor prognosis in hepatocellular carcinoma

Cited by 21 publications

References 30 publications

The role of fructose 1,6-bisphosphate-mediated glycolysis/gluconeogenesis genes in cancer prognosis

The role of fructose 1,6-bisphosphate-mediated glycolysis/gluconeogenesis genes in cancer prognosis

Incomptine A Induces Apoptosis, ROS Production and a Differential Protein Expression on Non-Hodgkin’s Lymphoma Cells

Prognostic Implications and Immune Infiltration Analysis of ALDOA in Lung Adenocarcinoma

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