Background: Overexpression of the NAD(P)H: Quinone Oxidoreductase 1 (NQOI) gene has been linked with tumor progression, aggressiveness, drug resistance, and poor patient prognosis. Most research has described the biological function of the NQO1 in certain types and limited samples, but a comprehensive understanding of the NQO1's function and clinical importance at the pan-cancer level is scarce. More research is needed to understand the role of NQO1 in tumor infiltration, and immune checkpoint inhibitors in various cancers are needed. Methods: The NQO1 expression data for 33 types of pan-cancer and their association with the prognosis, pathologic stage, gender, immune cell infiltration, the tumor mutation burden, microsatellite instability, immune checkpoints, enrichment pathways, and the half-maximal inhibitory concentration (IC50) were downloaded from public databases. Results: Our findings indicate that the NQO1 gene was significantly upregulated in most cancer types. The Cox regression analysis showed that overexpression of the NQO1 gene was related to poor OS in Glioma, uveal melanoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma, and adrenocortical carcinoma. NQO1 mRNA expression positively correlated with infiltrating immune cells and checkpoint molecule levels. The single-cell analysis revealed a potential relationship between the NQO1 mRNA expression levels and the infiltration of immune cells and stromal cells in bladder urothelial carcinoma, invasive breast carcinoma, and colorectal cancer. Conversely, a negative association was noted between various drugs (17-AAG, Lapatinib, Trametinib, PD-0325901) and the NQO1 mRNA expression levels. Conclusion: NQO1 expression was significantly associated with prognosis, immune infiltrates, and drug resistance in multiple cancer types. The inhibition of the NQO1-dependent signaling pathways may provide a promising strategy for developing new cancer-targeted therapies.

Liping Shen

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