Abstract
Overexpression of ALDH is associated with cancer stem-like features and poor cancer prognosis. High ALDH activity has been observed in cancer stem-like cells. There are a total of 19 human ALDH isoforms, all of which are associated with reducing oxidative stress and protecting cells from damage. However, it is unknown whether all ALDHs are associated with poor cancer prognosis and which ones play a significant role in cancer progression. In this study, we used RNA sequencing data from The Cancer Genome Atlas (TCGA) to evaluate the differential expression of 19 ALDH isoforms in 5 common human cancers. The 19 ALDH genes were analyzed with an integrating meta-analysis of cancer prognosis. Genotyping and next-generation RNA sequencing for 30 pairwise samples of head and neck squamous cell carcinoma were performed and compared with the TCGA cohort. The analysis showed that each ALDH isoform had a specific differential expression pattern, most of which were related to prognosis in human cancer. A lower expression of ALDH2 in the tumor was observed, which was independent from the ALDH2 rs671 SNP variant and the expression of other mitochondria-associated protein coding genes. This study provides new insight into the association between ALDH expression and cancer prognosis.
Highlights
Carcinogenesis is an extremely complicated process that may involve multilevel mutations such as karyotype changes, loss of heterogeneity, DNA copy-number variations, sequence mutations and aberrant mRNA and/or protein expression
From the The Cancer Genome Atlas (TCGA) database, the RNA sequencing (RNA-seq) data were extracted for samples of breast cancer (BRCA) (1097 tumor vs. 114 normal samples), lung adenocarcinoma (LUAD) (515 tumor vs. 59 normal samples), lung squamous cell carcinoma (LUSC) (502 tumor vs. 51 normal samples), esophageal squamous cell carcinoma (ESSC) (82 tumor vs. 8 normal samples) and head and neck squamous cell carcinomas (HNSCs) (520 tumor vs. 44 normal samples)
We used an integrated analysis to evaluate the differential expressions (DEs) for all ALDH isotypes as well as their correlation with cancer prognosis
Summary
Carcinogenesis is an extremely complicated process that may involve multilevel mutations such as karyotype changes, loss of heterogeneity, DNA copy-number variations, sequence mutations and aberrant mRNA and/or protein expression. In silico analysis has been commonly utilized in genomic studies, resulting in public microarray or RNA-seq datasets[1,18] These high-throughput bioinformatics tools can provide insight into the biological dynamics and functional validation of candidate genes. Prognoscan (http:// www.abren.net/PrognoScan/) is a bioinformatics tool that contains more than 70 microarray studies from 13 different human cancer types with clinical prognosis[21] It has been used widely for human cancer research[22,23,24,25] and provides a method to cross-link a group of candidate genes with prognoses in a systematic manner. The 30 pairwise head and neck squamous cell carcinomas (HNSCs) from Taiwanese patients were used to compare the ALDH2 genotype with the DEs and cancer prognosis
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