Distinct prognostic values of alcohol dehydrogenase mRNA expression in pancreatic adenocarcinoma

Liao, Xiwen; Huang, Rui; Liu, Xiaoguang; Han, Chuangye; Liu, Yu; Wang, Shijun; Sun, Na; Li, Bopei; Ning, Xin; Peng, Tao

doi:10.2147/ott.s140221

Cited by 21 publications

(29 citation statements)

References 61 publications

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“…Whereas, the expression of ADH5 were signi cantly upregulated in HCC tissues compared to normal liver tissues (Fig. 1E), consistent with what is already known in NSCLC, gastric cancer, and pancreatic adenocarcinoma [19,20,29]. In addition, previous studies have reported the positive correlation of ADHs with each other in numerous cancers [19,20]; here, our results also con rmed that in HCC (Fig.…”

Section: Discussionsupporting

confidence: 92%

“…Primarily, our results revealed that the expression levels of ADH1A-ADH4, and ADH6 were signi cantly decreased in HCC tissues compared to normal liver tissues (Fig. 1), which were similar to their expression in non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma [19,29]. Therefore, we speculate that ADH1A-ADH4, and ADH6 may serve as tumor suppressors in HCC.…”

Section: Discussionsupporting

confidence: 62%

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Prognostic Implications of Alcohol Dehydrogenases Inhepatocellular Carcinoma

Liu

Kong

et al. 2020

Preprint

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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. Results In our study, the expression profiles and corresponding clinical information of HCC from The Cancer Genome Atlas (TCGA) were used to evaluate the association between ADHs and outcomes of the patients. 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 Overall, our results provide the potential prognostic biomarkers or molecular targets for the patients with HCC.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 62%

Prognostic Implications of Alcohol Dehydrogenases Inhepatocellular Carcinoma

Liu

Kong

et al. 2020

Preprint

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“…Moreover, high expression levels of the ADH1A and ADH6 genes have a beneficial effect on the course of adenocarcinoma of the pancreas. Conversely, an increased activity of ADH5/FDH, oxidizing formaldehyde, has been noted by oncologists to be an unfavorable factor in the course of the disease . The same pattern was found in the study of patients with gastric cancer …”

Section: Genes Involved In the Metabolism Of Alcohols And Aldehydes supporting

confidence: 58%

“…Moreover, the authors suggested that the ADH1B, ADH1C, and ADH4 genes can function as tumor suppressors, while ADH5/FDH and ADH7 probably play an oncogenic role in the carcinogenesis of NSCLC. The analysis of isoenzymes of ADH is also of diagnostic value in brain cancer, stomach cancer, and adenocarcinoma of the pancreatic gland . Moreover, high expression levels of the ADH1A and ADH6 genes have a beneficial effect on the course of adenocarcinoma of the pancreas.…”

Section: Genes Involved In the Metabolism Of Alcohols And Aldehydes mentioning

confidence: 99%

Human Endogenous Formaldehyde as an Anticancer Metabolite: Its Oxidation Downregulation May Be a Means of Improving Therapy

Dorokhov

Sheshukova

Bialik³

et al. 2018

BioEssays

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Malignant cells are characterized by an increased content of endogenous formaldehyde formed as a by‐product of biosynthetic processes. Accumulation of formaldehyde in cancer cells is combined with activation of the processes of cellular formaldehyde clearance. These mechanisms include increased ALDH and suppressed ADH5/FDH activity, which oncologists consider poor and favorable prognostic markers, respectively. Here, the sources and regulation of formaldehyde metabolism in cancer cells are reviewed. The authors also analyze the participation of oncoproteins such as fibulins, FGFR1, HER2/neu, FBI‐1, and MUC1‐C in the control of genes related to formaldehyde metabolism, suggesting the existence of two mutually exclusive processes in cancer cells: 1) production and 2) oxidation and elimination of formaldehyde from the cell. The authors hypothesize that the study of the anticancer properties of disulfiram and alpha lipoic acid – which affect the balance of formaldehyde in the body – may serve as the basis of future anticancer therapy.

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“…MAK3/NAA30 , a component of the NatC complex ( Fig 8A ), induces p53-dependent apoptosis when knocked down in cancer cell lines [184]. The HLD-specific deletion enhancer, SFA1 , has seven human homologs, of which three ( ADH4, ADH1A , and ADH6 ) were UES in gCSI data ( Additional File 1, Figure S7) ‥ High expression of ADH1A or ADH6 was predictive of improved prognosis for pancreatic adenocarcinoma [185] and high expression of ADH1A or ADH4 had improved prognosis for non-small cell lung cancer [186]. The ERG13 homolog, GCS1 , has been suggested as a synthetic lethal target for BRAF V600E -positive human cancers [187], and HMGCS2 plays a role in invasion and metastasis in colorectal and oral cancer [188].…”

Section: Resultsmentioning

confidence: 99%

A yeast phenomic model for the influence of Warburg metabolism on genetic buffering of doxorubicin

Santos

Hartman

2019

Preprint

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Background: Saccharomyces cerevisiae represses respiration in the presence of adequate glucose, mimicking the Warburg effect, termed aerobic glycolysis. We conducted yeast phenomic experiments to characterize differential doxorubicin-gene interaction, in the context of respiration vs. glycolysis. The resulting systems level biology about doxorubicin cytotoxicity, including the influence of the Warburg effect, was integrated with cancer pharmacogenomics data to identify potentially causal correlations between differential gene expression and anti-cancer efficacy. Methods: Quantitative high-throughput cell array phenotyping (Q-HTCP) was used to measure cell proliferation phenotypes (CPPs) of the yeast gene knockout/knockdown library, treated with escalating doxorubicin concentrations in fermentable and non-fermentable media. Doxorubicin-gene interaction was quantified by departure of the observed and expected phenotypes for the doxorubicin-treated mutant strain, with respect to phenotypes for the untreated mutant strain and both the treated and untreated reference strain. Recursive expectation-maximization clustering (REMc) and Gene Ontology-based analyses of interactions were used to identify functional biological modules that buffer doxorubicin cytotoxicity, and to characterize their Warburg-dependence. Yeast phenomic data was applied to cancer cell line pharmacogenomics data to predict differential gene expression that causally influences the anti-tumor efficacy, and potentially the anthracycline-associated host toxicity, of doxorubicin. Results: Doxorubicin cytotoxicity was greater with respiration, suggesting the Warburg effect can influence therapeutic efficacy. Accordingly, doxorubicin drug-gene interaction was more extensive with respiration, including increased buffering by cellular processes related to chromatin organization, protein folding and modification, translation reinitiation, spermine metabolism, and fatty acid beta-oxidation. Pathway enrichment was less notable for glycolysis-specific buffering. Cellular processes exerting influence relatively independently, with respect to Warburg status, included homologous recombination, sphingolipid homeostasis, telomere tethering at nuclear periphery, and actin cortical patch localization. Causality for differential gene expression associated with doxorubicin cytotoxicity in tumor cells was predicted within the biological context of the phenomic model. Conclusions: Warburg status influences the genetic requirements to buffer doxorubicin toxicity. Yeast phenomics provides an experimental platform to model the complexity of gene interaction networks that influence human disease phenotypes, as in this example of chemotherapy response. High-resolution, systems level yeast phenotyping is useful to predict the biological influence of functional variation on disease, offering the potential to fundamentally advance precision medicine.

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Distinct prognostic values of alcohol dehydrogenase mRNA expression in pancreatic adenocarcinoma

Cited by 21 publications

References 61 publications

Prognostic Implications of Alcohol Dehydrogenases Inhepatocellular Carcinoma

Prognostic Implications of Alcohol Dehydrogenases Inhepatocellular Carcinoma

Human Endogenous Formaldehyde as an Anticancer Metabolite: Its Oxidation Downregulation May Be a Means of Improving Therapy

A yeast phenomic model for the influence of Warburg metabolism on genetic buffering of doxorubicin

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