Identification of TMEM71 as a hub NLRP3-related gene suppressing malignant behavior in nasopharyngeal carcinoma via the NLRP3/Caspase-1/GSDMD signaling pathway

Abstract

Objective

NLRP3 plays a key role in cellular pyroptosis and tumor progression. However, research on NLRP3-Related Genes (NRGs) in Nasopharyngeal Carcinoma (NPC) is limited.

Methods

We analyzed the GSE53819 dataset to identify genes positively correlated with NLRP3 mRNA and downregulated in NPC tumors, termed NRGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to characterize their biological functions. Validation was performed using the GSE64634 and GSE102349 datasets. The GSE102349 dataset was used to evaluate the impact of NRGs on the Progression-Free Survival (PFS) and their association with immune cell infiltration. A cohort of 421 NPC patients from a local hospital underwent multivariate Cox regression to assess the prognostic significance of hub NRGs. Cellular experiments further investigated the role of hub NRGs in NPC.

Results

In the GSE53819 dataset, 26 NRGs were identified, correlated with NLRP3 expression, and downregulated in tumor tissues. GO and KEGG analyses linked these 26 NRGs to the inflammasome complex. TMEM71, identified in the GSE64634 and GSE102349 datasets, was downregulated in tumor tissues and positively correlated with NLRP3 expression. It was the only NRG with prognostic value, with higher expression correlating with improved PFS. Immune cell infiltration analysis showed significant differences between high and low TMEM71 expression groups (e.g., naïve B cells). Local analysis confirmed that positive TMEM71 expression in tumor serves as an independent prognostic marker for NPC (HR = 0.53, 95% CI 0.366‒0.780). in vitro, TMEM71 activation of the NLRP3/caspase-1/GSDMD pathway suppressed malignant behaviors in NPC cell.

Conclusion

TMEM71 may serve as a prognostic biomarker for NPC and influence immune cell infiltration. Its overexpression could exert anticancer effects via the NLRP3/caspase-1/GSDMD pathway, highlight its potential as a therapeutic target in NPC.