Expression and correlation of NRF2, KEAP1, NQO-1 and HO-1 in advanced squamous cell carcinoma of the larynx and their association with clinicopathologic features

The present study aimed specifically investigate the expression and correlation of kelch-like ECH-associated protein-1 (KEAP1), nuclear factor (erythroid-derived 2)-like 2 (NRF2), quinone oxidoreductase-1 (NQO-1) and heme oxygenase-1 (HO-1) in laryngeal cancer and their association with clinicopathological features. A total of 33 paired human fresh advanced laryngeal cancer and adjacent normal specimens were collected following total laryngectomy. Immunohistochemical and immunoblotting analysis were performed to evaluate the expression of KEAP1, NRF2, NQO-1 and HO-1. All of the patients clinicopathologic features were collected. Immunohistochemistry indicated that NRF2-positive staining was as high as 79% (26/33) in the cancer samples and predominantly located in the nuclei, whereas positive expression of KEAP1, NQO-1 and HO-1 was detected in 70% (23/33), 76% (25/33) and 82% (27/33) of cancer tissues, respectively, and primarily expressed in the cytoplasm. The corresponding adjacent normal samples produced almost no or weak expression of the proteins. There were significant differences in protein expression between the two groups (P<0.01). Immunoblotting analysis also demonstrated that their expression levels were higher in cancer tissue compared with adjacent normal tissue. Notably, KEAP1, NQO-1 and HO-1 expression was positively correlated with nuclear NRF2 in cancer tissues, whereas they had no correlation with age, tumor stage (clinical stage III and IV), tumor size and lymph node metastasis. In conclusion, increased expression of NRF2, KEAP1, NQO-1 and HO-1 were common in advanced laryngeal cancer. Evaluation of these factors may have important clinical significance for the diagnosis and treatment of this disease.