Prognostic value of alcohol dehydrogenase mRNA expression in gastric cancer

Guo, Erna; Wei, Haotang; Liao, Xiwen; Xu, Yang; Li, Shu; Zeng, Xianmin

doi:10.3892/ol.2018.8007

Cited by 16 publications

(17 citation statements)

References 55 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%

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%

Prognostic Implications of Alcohol Dehydrogenases Inhepatocellular Carcinoma

Liu

Kong

et al. 2020

Preprint

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“…However, few studies have demonstrated the role of aberrant retinoid metabolism in drug-response. Previously, Guo et al showed that elevated expression levels of several genes involved in alcohol metabolism that also play a role in retinoid metabolism were associated with decreased mortality in gastric cancer patients receiving 5-FU-based chemotherapy (35). Our study demonstrates for the rst time in TNBC cell lines that the rate-limiting enzyme in retinoid metabolism, RDH10, signi cantly affects the intracellular concentration of ATRA (Fig.…”

Section: Discussionsupporting

confidence: 50%

RDH10 and ATRA sensitize triple-negative breast cancer to taxane-based chemotherapy through regulation of PIN1

Grainger

Zhang

et al. 2020

Preprint

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Background: With few targeted therapies available for triple-negative breast cancer (TNBC), there is a critical need to identify biomarkers that can predict chemotherapy-response. Copy number amplifications (CNAmps) have been implicated in tumorigenesis, progression, and treatment response. Previously, we performed a prospective neoadjuvant chemotherapy study (BEAUTY) and identified a 5 Mb CNAmp in TNBC patients associated with pathological complete response rates to taxane- and anthracycline-based chemotherapy. Here we further interrogated this amplicon and its role in chemotherapy response. Methods: Using siRNA screening of genes identified in the 5 Mb CNAmp, followed by cytotoxicity assays, we identified RDH10 significantly associated with chemo-sensitivity in TNBC cell lines. Functional studies were performed using RDH10 knockdown or overexpression followed by cytotoxicity, cell proliferation, luciferase reporter assays, HPLC or western blot.Results: RDH10 is a rate-limiting step involved in the synthesis of all-trans retinoic acid (ATRA) - the active metabolite of retinoid metabolism that is frequently aberrant in cancer. Previous studies demonstrated ATRA to be a potent inhibitor of PIN1, a key regulator of several oncogenic signaling pathways often amplified in TNBC. We discovered that genetic manipulation of RDH10 affected ATRA intracellular concentrations, contributing to PIN1 degradation and taxane-response. Furthermore, co-treatment of TNBC cells with ATRA significantly increased taxane-sensitivity.Conclusion: RDH10 amplification increases endogenous levels of ATRA and degrades PIN1 in TNBC. ATRA-mediated degradation of PIN1 sensitizes TNBC to chemotherapy, suggesting that RDH10 may be a novel biomarker of taxane response and the addition of ATRA to standard chemotherapy may improve chemo-sensitivity.

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“…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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Prognostic value of alcohol dehydrogenase mRNA expression in gastric cancer

Cited by 16 publications

References 55 publications

Prognostic Implications of Alcohol Dehydrogenases Inhepatocellular Carcinoma

Prognostic Implications of Alcohol Dehydrogenases Inhepatocellular Carcinoma

RDH10 and ATRA sensitize triple-negative breast cancer to taxane-based chemotherapy through regulation of PIN1

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

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