Transcriptomic and experimental validation identify biomarkers and regulatory mechanisms associated with the aryl hydrocarbon receptor in nasopharyngeal carcinoma

Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor of the nasopharyngeal mucosal epithelium. The aryl hydrocarbon receptor (AhR)—a widely distributed nuclear receptor regulating adaptive adverse responses—is confirmed carcinogenic upon activation. Thus, this study aims to identify novel biomarkers for NPC treatment.

Methods: Relevant data were obtained from public databases. Biomarkers were developed through the application of differential expression analysis, univariate Cox regression, and machine learning algorithms. Molecular mechanisms were then explored through immune infiltration and molecular regulatory networks. Additionally, the drug sensitivity analysis revealed potential differences in sensitivity to chemotherapy drugs. The experimental verification was conducted using reverse transcription quantitative polymerase chain reaction (RT-qPCR).

Results: Cholinergic receptor nicotinic beta 2 subunit (CHRNB2), adenylate cyclase 4 (ADCY4), and cell division cycle 6 (CDC6) were identified as biomarkers. CHRNB2 and CDC6 were highly expressed, while ADCY4 was lowly expressed in NPC. ADCY4 showed a significant positive correlation with plasmacytoid dendritic cells [correlation coefficient (cor) =0.48, P<0.001]. In contrast, CDC6 exhibited a strong negative correlation with central memory CD4 T cells (cor =−0.75, P<0.001), while CHRNB2 was significantly negatively correlated with activated B cells (cor =−0.50, P<0.001). A total of 9 microRNAs (hsa-miR-26a-5p) and 31 long non-coding RNAs (lncRNAs) (GAS5) associated with biomarkers were predicted. Patients with high ADCY4 expression demonstrated a higher half-maximal inhibitory concentration (IC₅₀) value for gemcitabine compared to those with low expression. However, the opposite trend was observed for CDC6 and CHRNB2.

Conclusions: This study identified CHRNB2, ADCY4, and CDC6 as candidate biomarkers and provided preliminary clues for further exploration of potential therapeutic strategies for NPC.