Overexpression of mediates doxorubicin resistance and predicts prognosis of pancreatic cancer.

Background: Dysregulation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) family is frequently observed in cancers and associated with their development and progression. However, the expression, role, and clinical significance of the NOX family members in pancreatic cancer remain unexplored.

Methods: The expression levels of the 7 NOX family genes were analyzed in Gene Expression Omnibus (GEO) datasets. The messenger RNA (mRNA) expression and gene alterations were explored using The Cancer Genome Atlas (TCGA) data portal. Clinical significance analyses of the NOX family genes were conducted among pancreatic cancer patients. The expression and prognostic value of () were then validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) in an independent validation cohort. The function of was analyzed by gene set enrichment analysis (GSEA) and its effect on the chemosensitivity of pancreatic cancer cells was detected by Cell Counting Kit-8 (CCK-8) assay.

Results: Results showed that (), and were upregulated, while NOX3 and NOX5 were downregulated in pancreatic cancer tissues compared with nontumor tissues. Genomic alteration analysis demonstrated that deregulation of NOX family genes was partially caused by genomic alterations. Survival analyses showed that only was associated with overall survival (OS) and relapse-free survival (RFS) of pancreatic cancer patients. The gene was observed to be markedly overexpressed in pancreatic cancer. In the GSEA results for pancreatic cancer patients, was significantly associated with oxidoreductase activity acting on nicotinamide adenine dinucleotide hydrogen (NADH) or NADPH and uridine 5'-diphospho-glucuronosyltansferase (UDP) glycosyltransferase activity. Knockdown of in pancreatic cancer cells increased their sensitivity to doxorubicin.

Conclusions: Overexpression of is correlated with prognosis and recurrence in pancreatic cancer patients and acts as a good marker for pancreatic cancer course prediction; furthermore, might be a therapeutic target for pancreatic cancer patients.