Abstract

Alcohol dehydrogenase iron containing 1 (ADHFE1) encodes a hydroxyacid-oxoacid transhydrogenase participating in multiple biological processes. The role of ADHFE1 in cancer has not been fully uncovered. Herein, we performed data analysis to investigate the expression of ADHFE1 and the underlying regulatory mechanisms, its relationship with cancer patients’ survival, and the relevant pathways in cancer. A range of recognized, web-available databases and bioinformatics tools were used in this in silico study. We found that ADHFE1 was frequently downregulated and hypermethylated in various cancer cell lines and tissue samples. High expression of ADHFE1 was positively associated with favorable patient prognosis in breast, colon, and gastric cancers. Pathway analysis revealed its potential role in cancer-related biological processes, including energy metabolism, DNA replication, and cell cycle regulation. AHDFE1 mRNA expression and DNA methylation can potentially be used as diagnostic markers in cancer and might be of great value in predicting the survival of patients with cancer.

Highlights

  • Cancer is expected to rank as the leading cause of death and the single most barrier to increasing life expectancy worldwide [1]

  • The single protein of ADHFE1 was used as the searching input, and active protein interaction sources were from textmining, experiments, databases, co-expression, neighborhood, Dysregulation of ADHFE1 was observed in several types of human cancer, and DNA methylation might be a major contributor [7,8,9,23,24,25,26]

  • We validated the prognostic value of ADHFE1 in the TCGA-Stomach Adenocarcinoma (STAD) dataset using SurvExpress that patients with gastric cancer in low-risk subgroup had higher expression of ADHFE1 than those in the high-risk subgroup (P = 3.77 × 10−114; Figure 5g). These results suggest that gastric cancer has significant ADHFE1 downregulation which is significantly related to DNA methylation but not copy number alterations (CNAs), and ADHFE1 expression is negatively correlated with the overall survival of patients with gastric cancer

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Summary

Introduction

Cancer is expected to rank as the leading cause of death and the single most barrier to increasing life expectancy worldwide [1]. The incidence and mortality of cancer are Alcohol dehydrogenase iron containing 1 (ADHFE1) was first cloned and characterized by Deng from the human fetal brain cDNA library [3]. ADHFE1 is localized in mitochondria and exhibits differentiation-dependent expression during in vitro brown and white adipogenesis, indicating its role in adipocyte function and energy metabolism [6]. It was reported that in colorectal cancer (CRC), ADHFE1 was hypermethylated, and a high expression level of ADHFE1 was positively associated with tumor differentiation, indicating its tumor-suppressing function in CRC [8]. ADHFE1 has been reported to form a mutual regulatory loop with MYC, and ADHFE1 may play an oncogenic role in breast cancer via inducing metabolic reprogramming [10]

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