Targeting NLRC4 for potential therapeutic strategies in lung adenocarcinoma.

BACKGROUND

Autophagy, a vital cellular process, plays a significant role in the development of a spectrum of diseases, notably cancer. The objective of this study was to assess the prognostic significance and explore the possible roles of autophagy-related genes (ARGs) in lung adenocarcinoma (LUAD) and in 33 cancer types.

METHODS

In this study, ARGs were sourced from the Human Autophagy Database (HADb), with gene expression data retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The LASSO Cox and multivariate Cox regression models were employed to identify ARGs with prognostic significance, leading to the development of the Autophagy-Related Gene Prognostic Signature (ARGPS), which was compared with previously established prognostic models. The associations between the ARGPS and clinical parameters were examined to identify independent prognostic factors. Additionally, a pan-cancer analysis underscored the role of the ARGPS in immune subtyping, the tumor immune context, survival outcomes, stemness scores, and sensitivity to antitumor drugs. Finally, a virtual drug screening was performed to predict potential target interactions.

RESULTS

In the GSE116959 dataset, we identified 14 DEARGs with statistical significance (p < 0.05 and |logFC|> 1). Using LASSO Cox and multivariate Cox regression, we developed an independent prognostic signature, identifying seven ARGs to form the ARGPS. LUAD patients were stratified into low-risk and high-risk groups. Pan-cancer analysis highlighted significant heterogeneity in ARGPS expression among various cancers. ARGPS members were significantly correlated with immune infiltration, drug resistance, and stemness in tumors. Virtual screening identified five potential NLRC4-targeting drugs for LUAD treatment.

CONCLUSIONS

In this study, we developed a predictive risk model based on seven ARGs. We comprehensively examined ARGPS expression and its correlation with immune infiltration and the tumor microenvironment. These findings could inform targeted immunotherapy and chemotherapy for LUAD and other cancers. The low expression of NLRC4 in LUAD indicated its potential as a therapeutic target.