Distinct Prognostic Values of Alcohol Dehydrogenase Family Members for Non-Small Cell Lung Cancer

Abstract

BACKGROUND Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death worldwide. The relationships of alcohol dehydrogenase (ADH) enzymes, encoded by the genes ADH1 (1A), ADH1B (ADH2), ADH1C (ADH3), ADH4, ADH5, ADH6, and ADH7, with NSCLC have not been studied. The aim of this study was to explore the associations between NSCLC prognosis and the expression patterns of ADH family members. MATERIAL AND METHODS The online resource Metabolic gEne RApid Visualizer was used to assess the expression patterns of ADH family members in normal and primary lung tumor tissues. The GeneMANIA plugin of Cytoscape software and STRING website were used to evaluate the relationships of the 7 ADH family members at the gene and protein levels. Gene ontology enrichment analysis and KEGG pathway analysis were performed using DAVID. The online website Kaplan-Meier Plotter was used to construct survival curves between NSCLC and ADH isoforms. RESULTS The prognosis of patients with high expression levels of the ADH1B, ADH1C, ADH4, and ADH5 genes was better than those with low expression in adenocarcinoma and all (containing adenocarcinoma and squamous cell cancer) histological types (all P<0.05). Low expression of ADH7 was associated with a better prognosis in patients with both the adenocarcinoma and squamous cell cancer histological types (P=9e-05). Moreover, expression of ADH family members was associated with smoking status, clinical stage, and chemotherapy status. CONCLUSIONS ADH1B, ADH1C, ADH4, ADH5, and ADH7 appear to be useful biomarkers for the prognosis of NSCLC patients.

Figure 1

Expression levels of ADH family members in normal and primary lung tumor tissues. (A) Expression levels of ADH1A in normal and primary lung tumor tissues; (B) Expression levels of ADH1B in normal and primary lung tumor tissues; (C) Expression levels of ADH1C in normal and primary lung tumor tissues; (D) Expression levels of ADH4 in normal and primary lung tumor tissues; (E) Expression levels of ADH5 in normal and primary lung tumor tissues; (F) Expression levels of ADH6 in normal and primary lung tumor tissues; (G) Expression levels of ADH7 in normal and primary lung tumor tissues.

Figure 2

Interaction analysis of ADH family members. (A) Pearson correlation of ADH family members in lung adenocarcinoma; (B) Pearson correlation of ADH family members in lung SCC; (C) Gene-gene interaction network among ADH family members; (D) Protein-protein interaction network among ADH family members.

Figure 3

Survival analysis of ADH1A (207820_at) in NSCLC. (A) Survival analysis of ADH1A in both adenocarcinoma and squamous cell cancer; (B) Survival analysis of ADH1A in adenocarcinoma; (C) Survival analysis of ADH1A in squamous cell cancer.

Figure 4

Survival analysis of ADH1B (209612_at) in NSCLC. (A) Survival analysis of ADH1B in both adenocarcinoma and squamous cell cancer; (B) Survival analysis of ADH1B in adenocarcinoma; (C) Survival analysis of ADH1B in squamous cell cancer.

Figure 5

Survival analysis of ADH1C (206262_at) in NSCLC. (A) Survival analysis of ADH1C in both adenocarcinoma and squamous cell cancer; (B) Survival analysis of ADH1C in adenocarcinoma; (C) Survival analysis of ADH1C in squamous cell cancer.

Figure 6

Survival analysis of ADH4 (223781_at) in NSCLC. (A) Survival analysis of ADH4 in both adenocarcinoma and squamous cell cancer; (B) Survival analysis of ADH4 in adenocarcinoma; (C) Survival analysis of ADH4 in squamous cell cancer.

Figure 7

Survival analysis of ADH5 (208847_at) in NSCLC. (A) Survival analysis of ADH5 in both adenocarcinoma and squamous cell cancer; (B) Survival analysis of ADH5 in adenocarcinoma; (C) Survival analysis of ADH5 in squamous cell cancer.

Figure 8

Survival analysis of ADH6 (207544_at) in NSCLC. (A) Survival analysis of ADH6 in both adenocarcinoma and squamous cell cancer; (B) Survival analysis of ADH6 in adenocarcinoma; (C) Survival analysis of ADH6 in squamous cell cancer.

Figure 9

Survival analysis of ADH7 (210505_at) in NSCLC. (A) Survival analysis of ADH7 in both adenocarcinoma and squamous cell cancer; (B) Survival analysis of ADH7 in adenocarcinoma; (C) Survival analysis of ADH7 in squamous cell cancer.