Prognostic significance of pyroptosis-related factors in lung adenocarcinoma

Abstract

Background: Numerous studies have revealed that the abnormal expression of pyroptosis-related genes is closely related to the prognosis of lung adenocarcinoma (LUAD); however, a comprehensive analysis has yet to be conducted. This study aimed to reveal the influence of pyroptosis-related genes on the prognosis of LUAD and establish a prognostic model based on those genes, in order to evaluate the prognosis of LUAD. Methods:The data of tumor and normal samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential analysis was used to identify pyroptosis-related genes (obtained from the GeneCards database) that were differentially expressed (DE) in TCGA database. Univariate and stepwise multivariate Cox proportional hazards regression analyses were used to screen feature genes related to LUAD overall survival (OS) and construct gene signature. Gene set enrichment analysis (GSEA) was then performed to reveal potential functions related to gene signature.Finally, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to reveal distinctions in each cell-subtype groups in the immune landscape of LUAD.Results: Overall, 26 DE genes (DEGs) associated with pyroptosis were obtained. Among them, 4 (MKI67, BTK, MST1, and TUBB6) were selected as prognostic genes and a 4-gene signature with a good prognostic performance in the TCGA and GEO was constructed. The gene signature was shown to be an independent prognostic factor of LUAD in subsequent analysis. Functional enrichment indicated that the 4-gene signature may participate in the tumorigenesis and development of LUAD through various pathways related to tumor progression to play a prognostic role in LUAD. Additionally, the results of the immune landscape indicated that the 4-gene signature may affect the prognosis of LUAD via cooperating with changes in the immune microenvironment. Conclusions:The key biomarkers and pathways identified in this study would deepen the comprehension of the molecular mechanism of pyroptosis in LUAD. More importantly, the 4-gene signature may serve as a novel potential prognostic model for LUAD.

Identification of macrophage-related genes correlated with prognosis and immunotherapy efficacy in non-small cell lung cancer

“…Tubulin plays a crucial role in tumorigenesis and has shown potential prognostic value in various solid tumours [ 36 , 37 ]. Recent studies have demonstrated that TUBB6 (tubulin beta 6 class V) promotes the growth of cancer tissue in multiple solid tumours and serves as an important prognostic factor [ [38] , [39] , [40] ]. Our findings further support this concept.…”

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“…At present, with the development of microarray and sequencing technology, genetic testing technology is becoming increasingly common. Based on bioinformatics approach, one study explored a prognostic model for lung adenocarcinoma from the perspective of pyroptosis-related factors (Lin et al, 2022), and one study explored a prognostic model for IPF from the perspective of immune-related chromatin regulatory genes (Li et al, 2022). However, translating the clinical and prognostic value of EMT-related genes to IPF requires extensive research.…”

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