Abstract
The aldehyde dehydrogenase 2 point mutation (ALDH2*2) is a common frequent human gene variant, especially in East Asians. However, the expression and mechanism of action of ALDH2 in HNSC remain unknown. The present study explored the clinical significance and immune characteristics of ALDH2 in HNSC. The receiver operating characteristic curve was analysed to assess the diagnostic value of ALDH2 expression. ALDH2 expression in normal tissues and HNSC tissues was evaluated by IHC, and we also analysed ALDH2 gene expression in 4 HNSC cell lines. ALDH2 expression was significantly reduced in HNSC tissues compared to normal tissues (p < 0.05). HNSC patients with high ALDH2 expression had a better prognosis compared to patients with low ALDH2 expression (p < 0.05). GSEA indicated that these gene sets were correlated with signalling pathways, including the JAK-STAT signalling pathway. Unexpectedly, we found a significant prognostic effect of ALDH2 for HNSC based on alcohol consumption and the male sex. The correlation between ALDH2 expression and immune inhibitors showed an effect for ALDH2 in modifying tumour immunology in HNSC, and there may be a possible mechanism by which ALDH2 regulates the functions of T cells in HNSC. In addition, we developed a prognostic nomogram for HNSC patients, which suggested that low ALDH2 expression indicated poor prognosis in HNSC patients who were males and alcoholics.
Highlights
Head and neck squamous carcinoma (HNSC) is the eighth most common malignancy according to the information reported in Global Cancer Statistics 2 0211
The percentages of the different HNSC stages were as follows: Stage I HNSC cases accounted for 3.90%19; Stage II cases accounted for 19.50% [95]; Stage III cases accounted for 20.90% [102]; and Stage IV cases accounted for 55.80% [272]
Reactome pathway analysis revealed significant enrichment in the VEGFA-VEGFR2 pathway, death receptor signalling and adaptive immune system pathways (Fig. 5E). These results indicated that Acetaldehyde dehydrogenase 2 (ALDH2) expression is correlated with complicated oncogenic pathway hyperactivation in head and neck squamous carcinoma, especially signalling that correlates with cell proliferation and the immune system
Summary
Head and neck squamous carcinoma (HNSC) is the eighth most common malignancy according to the information reported in Global Cancer Statistics 2 0211. Key biomarkers that can be used to enhance the prognosis of patients with head and neck squamous cell carcinoma remain to be confirmed. ALDH2 is acknowledged for its alcohol oxidation among many aldehyde dehydrogenase genes, and approximately 30% to 40% of Asians have genetic defects in this enzyme. ALDH2 gene defects are correlated with an increased risk of hepatocellular carcinoma in patients with hepatitis B cirrhosis due to excessive alcohol c onsumption[3]. We explored ALDH2 expression in numerous neoplasms using The Cancer Genome Atlas (TCGA) and its association with HNSC patient prognosis. Our research provides new insights into the function of ALDH2 in head and neck squamous cell carcinoma
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