Identification of the pyroptosis‑related prognostic gene signature and the associated regulation axis in lung adenocarcinoma

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.

Identification of a Pyroptosis-Related Gene Signature for Predicting Overall Survival and Response to Immunotherapy in Hepatocellular Carcinoma

“…The risk score generated from the gene signature was shown to be an independent risk factor for poor prognosis. Similar to our results, prior studies have also proved the prognostic roles of pyroptosis-related genes in lung cancer and ovarian cancer (Lin et al, 2021;Ye et al, 2021). GSDME, also known as deafness autosomal dominant 5 (DFNA5), one of the genes from our gene signature, was first identified for its involvement in inherited hearing impairment ( Van Laer et al, 1998).…”

“…NLRP3 inflammasome may also drive liver injury and fibrosis and may contribute to the development of liver cancer ( Wree et al, 2018 ). More recently, the pyroptosis-related gene signatures for ovarian cancer and lung cancer has been proved to be prognostic ( Lin et al, 2021 ; Ye et al, 2021 ). Interestingly, pyroptosis-induced inflammation was found to synergize with anti-PD1 therapy through triggering antitumour immunity ( Wang et al, 2020 ).…”

Bioinformatics Identification of Ferroptosis-Related Biomarkers and Therapeutic Compounds in Ischemic Stroke

“…Ferroptosis is a new form of programmed cell death characterized by abundant iron accumulation and lipid peroxidation during the cell death process (5). Recent evidence revealed that ferroptosis was involved in the tumorigenesis and progression of cancer (6)(7)(8). Interestingly, ferroptosis was considered to play a vital role in many diseases, including ischemic stroke and heart diseases (9,10).…”

Identification and validation of a pyroptosis-related prognostic signature for thyroid cancer

“…Pyroptosis-related genes also play an important role in tumor immunity and can be used to predict the prognosis of ovarian cancer [ 15 ]. A prognostic signature for lung adenocarcinoma was built based on pyroptosis-related regulators [ 16 ]. However, the prognostic value of pyroptosis-related genes in THCA has not yet been elucidated.…”