Aldehyde dehydrogenase 1 (ALDH1) isoform expression and potential clinical implications in hepatocellular carcinoma

Abstract

<div><p>Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was assessed using the OncoLnc database. The expression levels of ALDH1 isoforms in normal liver tissues and clinical specimens of cancer <i>vs</i>. normal control datasets were determined using the GTEx and Oncomine databases, respectively. We then analyzed the prognostic value of ALDH1 expression in 212 hepatitis B virus (HBV)–related HCC patients using the GEO database. We found that the ALDH1 isoform showed high aldehyde dehydrogenase activity. The <i>ALDH1A1</i>, <i>ALDH1B1</i>, and <i>ALDH1L1</i> genes encoded for the ALDH1 enzyme. High <i>ALDH1B1</i> expression had protective qualities in HCC patients. Moreover, HBV–related HCC patients who showed high <i>ALDH1L1</i> gene expression had a better clinical outcomes. In addition, high <i>ALDH1A1</i> expression was associated with a 57–month recurrence–free survival in HBV-related HCC patients. High <i>ALDH1B1</i> expression was protective for HCCs with multiple nodules and high serum alpha–fetoprotein (AFP) level. Furthermore, high serum AFP levels contributed to lower <i>ALDH1L1</i>. <i>ALDH1A1</i>, <i>ALDH1B1</i>, and <i>ALDH1L1</i>, all of which were considered promising diagnostic and prognostic markers as well as potential drug targets.</p></div