Prognostic implications of alcohol dehydrogenases in hepatocellular carcinoma

Abstract

Background Hepatocellular carcinoma (HCC) is a malignancy with high incidence and mortality rates worldwide. Alcohol dehydrogenases (ADHs) are huge family of dehydrogenase enzymes and associated with the prognosis of various cancers. However, comprehensive analysis of prognostic implications related to ADHs in HCC is still lacking and largely unknown. Methods The expression profiles and corresponding clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test was employed to evaluate the expression of ADHs. Cox regression and Kaplan-Meier analyses were used to investigate the association between clinicopathological characteristics and survival. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were performed and visualized using R/BiocManager package. Results We found that the expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly downregulated in HCC samples compared to normal liver samples. Our univariate and multivariate Cox regression analyses results showed that high expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was considered as an independent factor with an improved prognosis for the survival of HCC patients. Moreover, our Kaplan-Meier analysis results also revealed that high expression of AHD1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly associated with good survival rate in HCC patients. In addition, GO, KEGG, and GSEA analyses unveiled several oncogenic signaling pathways were negatively associated high expression of ADHs in HCC. Conclusion In the present study, our results provide the potential prognostic biomarkers or molecular targets for the patients with HCC.

Pairwise correlation of genes involved in glucose metabolism: a potential diagnostic marker of cancer?

“…ADH1B encodes alcohol dehydrogenase 1B, which catalyzes the oxidation of alcohol to form acetaldehyde. ADH1B is downregulated in hepatocellular carcinoma [ 18 ] and its polymorphism is associated with increased risk for various types of cancer, such as colorectal cancer, gastric cancer, and esophageal cancer [ 19 - 21 ]. We further performed survival analysis and generated Kaplan-Meier plots for ADH1B for the 12 types of cancer (Figure 1 ).…”

Identification of factors regulating the gene expression of alcohol dehydrogenases in hepatocellular carcinoma

“…Previous study assessed the gene expression of ADH family members in TCGA data, and demonstrated that ADH1A, ADH1B, ADH1C, ADH4, and ADH6 expression were signi cantly decreased in HCC tissues compared with normal controls [10]. In the present study, we further analyzed the transcriptome expression level of all ADH genes in 20 liver cancer and 12 tumor adjacent normal tissues by employing GEO dataset.…”

“…ADHs are encoded by seven ADH genes that locate in a segment of ∼370 kb on chromosome 4 (4q21) and are transcribed in the order of ADH7, ADH1C, ADH1B, ADH1A, ADH6, ADH4 and ADH5 [8,9]. Of note, the gene expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 has been identi ed to be strongly decreased in HCC patients [10], revealing the importance of ADH expression in association with the increased risk of liver cancer. Nevertheless, the mechanisms responsible for the modulated level of ADH gene expression remains elusive.…”

Comprehensive analyses of competing endogenous RNA networks reveal potential biomarkers for predicting hepatocellular carcinoma recurrence

“…Similar to that in our study, HCC patients with lower ADH4 expression had shorter survival time, and multivariate Cox analysis showed that ADH4 expression was an independent predictor of prognosis. Liu XY et al [ 34 ] comprehensively analyzed the prognostic implications related to ADH family genes in HCC using bioinformatic methods. As a result, they found that the expression of ADH4 was significantly downregulated in HCC tissues compared to normal tissues.…”