The potential of the NLRC4 Inflammasome as a Cancer biomarker: A Pan-cancer investigation

Abstract

Background

The innate immune response, crucial for detecting microbial threats, relies on pattern recognition receptors like NLRC4 (NOD-like receptor family CARD domain-containing protein 4). NLRC4 triggers inflammasome assembly upon detecting bacterial flagellin and needle protein, releasing pro-inflammatory cytokines. Recent research emphasizes NLRC4 inflammasomes' role in malignancies, indicating their impact on cancer progression and immune regulation.

Methods

To comprehensively investigate the genetic variability, therapeutic implications, and biological relevance of NLRC4 across human cancers, we conducted a pan-cancer analysis utilizing diverse bioinformatics tools including different omics data. These tools included GEPIA, Kaplan-Meier Plotter, cBioPortal, TIMER2.0, Enrichr, Human Protein Atlas, IID, MuTarget Analysis, MAGIC, TargetScan, and CTD. Our analysis aimed to elucidate NLRC4 expression patterns, survival outcomes, pathway enrichment, regulatory mechanisms, and associations with genetic alterations and immune infiltration in various cancer subtypes.

Results

Our findings revealed a widespread upregulation of NLRC4 expression in 19 out of 31 major human cancer subtypes, with significant correlations observed with overall survival (OS) in SARC and THCA, and relapse-free survival (RFS) in HNSC, KIRP, and PAAD. Enrichment analyses identified intricate connections between NLRC4-associated genes and diverse biological pathways. Additionally, miRNAs, hub genes, and transcription factors regulating NLRC4 emerged as key players in cancer pathogenesis.

Conclusions

Our study highlights NLRC4's potential as a pan-cancer biomarker and therapy focus in human cancers. Associations with survival outcomes, pathways, and regulatory networks illuminate NLRC4's multifaceted cancer role, urging a deeper investigation into its mechanisms and therapeutic potential for patient benefit.