Abstract
Lung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. Pyroptosis could regulate tumour cell proliferation, invasion, and metastasis, thereby affecting the prognosis of cancer patients. However, the role of pyroptosis-related genes (PRGs) in LUAD remains unclear. In our study, comprehensive bioinformatics analysis was performed to construct a prognostic gene model and ceRNA network. The correlations between PRGs and tumour-immune infiltration, tumour mutation burden, and microsatellite instability were evaluated using Pearson’s correlation analysis. A total of 23 PRGs were upregulated or downregulated in LUAD. The genetic mutation variation landscape of PRG in LUAD was also summarised. Functional enrichment analysis revealed that these 33 PRGs were mainly involved in pyroptosis, the NOD-like receptor signalling pathway, and the Toll-like receptor signalling pathway. Prognosis analysis indicated a poor survival rate in LUAD patients with low expression of NLRP7, NLRP1, NLRP2, and NOD1 and high CASP6 expression. A prognostic PRG model constructed using the above five prognostic genes could predict the overall survival of LUAD patients with medium-to-high accuracy. Significant correlation was observed between prognostic PRGs and immune-cell infiltration, tumour mutation burden, and microsatellite instability. A ceRNA network was constructed to identify a lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis in LUAD. In conclusion, we performed a comprehensive bioinformatics analysis and identified a prognostic PRG signature containing five genes (NLRP7, NLRP1, NLRP2, NOD1, and CASP6) for LUAD patients. Our results also identified a lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis, which may also play an important role in the progression of LUAD. Further study needs to be conducted to verify this result.
Highlights
Lung cancer remains the most common deadly disease, with an estimated 2.09 million new cases and 1.76 million deaths each year [1]
Defining of the expression of pyroptosis-related genes (PRGs) in Lung adenocarcinoma (LUAD) We first explored the expression of the 33 PRGs in LUAD and normal lung tissues using the The Cancer Genome Atlas (TCGA) LUAD dataset
The expression of PRKACA, NOD1, NLRP1, ELANE, TNF, IL1B, IL18, PYCARD, CASP5, NLRC4, NLRP3, IL6, and CASP1 was increased, while the expression of GSDMB, PJVK, CASP4, NLRP7, CASP3, CASP6, CASP8, GSDMA, GSDMC, and AIM2 was decreased in LUAD compared with normal tissues (Fig. 1A, all
Summary
Lung cancer remains the most common deadly disease, with an estimated 2.09 million new cases and 1.76 million deaths each year [1]. Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer, accounting for approximately 40% of all cases [2]. Chemoradiotherapy, targeted therapy, and immunotherapy being used in the treatment of lung cancer, the prognosis remains disheartening [3], and 5-year survival ranges from 4 to 17%, depending on disease and treatment differences [4]. Many biomarkers or gene signatures have been found to have the potential to predict the prognosis of LUAD, they are still in the molecular research phase and have not yet been applied in clinical practice. Uncovering prognostic gene signatures for the prognosis of LUAD would be of great significance
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