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Distinct prognostic values of alcohol dehydrogenase mRNA expression in pancreatic adenocarcinoma.

ABSTRACT: Alcohol dehydrogenase (ADH) isoenzymes have been reported as a potential diagnostic marker for pancreatic cancer, but their prognostic value in pancreatic cancer remains unclear. The aim of this investigation was to identify the prognostic value of ADH genes in human patients with pancreatic adenocarcinoma (PAAD).An RNA sequencing dataset and corresponding survival profiles of PAAD were obtained from The Cancer Genome Atlas. Survival analysis and gene set enrichment analysis were used to investigate the prediction value and potential mechanism of ADH genes in PAAD prognosis.Survival analysis of ADH genes suggests that a high expression of ADH1A (adjusted P=0.037, adjusted hazard ratio [HR] =0.627, 95% CI =0.404-0.972) and ADH6 (adjusted P=0.018, adjusted HR =0.588, 95% CI =0.378-0.914) were associated with a significantly decreased risk of death, while a high expression of ADH5 was associated with a significantly increased risk of death (adjusted P=0.043, adjusted HR =1.564, 95% CI =1.013-2.414). Joint effects analysis of three ADH gene prognostic markers suggests that the prognosis difference for any marker combination was more significant than that for any individual marker. The potential mechanism of ADH1A and ADH6 in PAAD prognosis was that a high expression of ADH1A and ADH6 was involved in the P450 pathway and biological processes, while high ADH5 expression was involved in transforming growth factor β regulation-related pathways and biological processes, Wnt, the cell cycle, ErbB, and mitogen-activated protein kinase signaling pathways.Our data suggest that ADH1A, ADH5, and ADH6 expression may be potential prognostic markers of PAAD and in combination have a strong interaction and better predictive value for PAAD prognosis.

SUBMITTER: Liao X

PROVIDER: S-EPMC5533474 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:Previous studies have reported that alcohol dehydrogenase (ADH) isoenzymes possess diagnostic value in gastric cancer (GC). However, the prognostic value of ADH isoenzymes in GC remains unclear. The aim of the present study was to identify the prognostic value of ADH genes in patients with GC. The prognostic value of ADH genes was investigated in patients with GC using the Kaplan-Meier plotter tool. Kaplan-Meier plots were used to assess the difference between groups of patients with GC with different prognoses. Hazard ratios (HR) and 95% confidence intervals (CI) were used to assess the relative risk of GC survival. Overall, 593 patients with GC and 7 ADH genes were included in the survival analysis. High expression of ADH 1A (class 1), ? polypeptide (ADH1A; log-rank P=0.043; HR=0.79; 95% CI: 0.64-0.99), ADH 1B (class 1), ? polypeptide (ADH1B; log-rank P=1.9×10-05; HR=0.65; 95% CI: 0.53-0.79) and ADH 5 (class III), ? polypeptide (ADH5; log-rank P=0.0011; HR=0.73; 95% CI: 0.6-0.88) resulted in a significantly decreased risk of mortality in all patients with GC compared with patients with low expression of those genes. Furthermore, protective effects may additionally be observed in patients with intestinal-type GC with high expression of ADH1B (log-rank P=0.031; HR=0.64; 95% CI: 0.43-0.96) and patients with diffuse-type GC with high expression of ADH1A (log-rank P=0.014; HR=0.51; 95% CI: 0.3-0.88), ADH1B (log-rank P=0.04; HR=0.53; 95% CI: 0.29-0.98), ADH 4 (class II), ? polypeptide (log-rank P=0.033; HR=0.58; 95% CI: 0.35-0.96) and ADH 6 (class V) (log-rank P=0.037; HR=0.59; 95% CI: 0.35-0.97) resulting in a significantly decreased risk of mortality compared with patients with low expression of those genes. In contrast, patients with diffuse-type GC with high expression of ADH5 (log-rank P=0.044; HR=1.66; 95% CI: 1.01-2.74) were significantly correlated with a poor prognosis. The results of the present study suggest that ADH1A and ADH1B may be potential prognostic biomarkers of GC, whereas the prognostic value of other ADH genes requires further investigation.

Project description:The integrin α (ITGA) subfamily genes play a fundamental role in various cancers. However, the potential mechanism and application values of ITGA genes in colon adenocarcinoma (COAD) remain elusive. The present study investigated the significance of the expression of ITGA genes in COAD from the perspective of diagnosis and prognosis. A COAD RNA‑sequencing dataset was obtained from The Cancer Genome Atlas. The present study investigated the biological function of the ITGA subfamily genes through bioinformatics analysis. Reverse transcription‑quantitative polymerase chain reaction was applied to investigate the distribution of integrin α8 (ITGA8) expression in COAD tumors and adjacent normal tissues. Bioinformatics analysis indicated that ITGA genes were noticeably enriched in cell adhesion and the integrin‑mediated signaling pathway, and co‑expressed with each other. It was also revealed through observation that the majority of gene expression was significantly low in tumor tissues (P<0.05), and diagnostic receiver operating characteristic curves revealed that most of the genes could serve as significant diagnostic markers in COAD (P<0.05), especially ITGA8 which had a high diagnostic value with an area under curve (AUC) of 0.989 [95% confidence interval (CI) 0.980‑0.997] in COAD (P<0.0001). In addition, ITGA8 expression was verified in clinical samples and it was revealed that it was higher in adjacent normal tissues (P=0.041) compared to COAD tissues, and the AUC was 0.704 (95% CI, 0.577‑0.831; P<0.0085). Multivariate survival analysis indicated that integrin α (ITGA5) may be an independent prognostic indicator for COAD overall survival. Gene set enrichment analysis indicated that ITGA5 may participate in multiple biological processes and pathways. The present study revealed that ITGA genes were associated with the diagnosis and prognosis of COAD. The mRNA expression of ITGA8 may be a potential diagnosis biomarker and ITGA5 may serve as an independent prognosis indicator for COAD.

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Distinct prognostic values of alcohol dehydrogenase mRNA expression in pancreatic adenocarcinoma.

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