Identification and Validation of the Pyroptosis-Related Molecular Subtypes of Lung Adenocarcinoma by Bioinformatics and Machine Learning

Abstract

Lung cancer remains the leading cause of cancer death globally, with lung adenocarcinoma (LUAD) being its most prevalent subtype. Due to the heterogeneity of LUAD, patients given the same treatment regimen may have different responses and clinical outcomes. Therefore, identifying new subtypes of LUAD is important for predicting prognosis and providing personalized treatment for patients. Pyroptosis-related genes play an essential role in anticancer, but there is limited research investigating pyroptosis in LUAD. In this study, 33 pyroptosis gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. By bioinformatics and machine learning analyses, we identified novel subtypes of LUAD based on 10 pyroptosis-related genes and further validated them in the GEO dataset, with machine learning models performing up to an AUC of 1 for classifying in GEO. A web-based tool was established for clinicians to use our clustering model (http://www.aimedicallab.com/tool/aiml-subphe-luad.html). LUAD patients were clustered into 3 subtypes (A, B, and C), and survival analysis showed that B had the best survival outcome and C had the worst survival outcome. The relationships between pyroptosis gene expression and clinical characteristics were further analyzed in the three molecular subtypes. Immune profiling revealed significant differences in immune cell infiltration among the three molecular subtypes. GO enrichment and KEGG pathway analyses were performed based on the differential genes of the three subtypes, indicating that differentially expressed genes (DEGs) were involved in multiple cellular and biological functions, including RNA catabolic process, mRNA catabolic process, and pathways of neurodegeneration-multiple diseases. Finally, we developed an 8-gene prognostic model that accurately predicted 1-, 3-, and 5-year overall survival. In conclusion, pyroptosis-related genes may play a critical role in LUAD, and provide new insights into the underlying mechanisms of LUAD.

Identification of SMIM1 and SEZ6L2 as Potential Biomarkers for Genes Associated with Intervertebral Disc Degeneration in Pyroptosis

“…This article included 81 genes related to pyroptosis based on previous studies [ 16 – 18 ]. We searched for genes associated with pyroptosis in DEGs by mapping Venn diagrams ( http://bioinformatics.psb.ugent.be/webtools/Venn/ ).…”

Integratively Genomic Analysis Reveals the Prognostic and Immunological Characteristics of Pyroptosis and Ferroptosis in Pancreatic Cancer for Precision Immunotherapy

“…Some strengths could be noticed in our study. This study is more valuable and convincing when compared with other studies that only focused on pyroptosis-or ferroptosis-related genes (Tang et al, 2020a;Fu and Song, 2021;Liu et al, 2021). Different from one recent study that clustered the hepatocellular carcinoma based on the prognosis-related genes associated with ferroptosis and pyroptosis, this study stratified cell death subtypes based on dual analysis of pyroptosis-and ferroptosis-related genes and further established a scoring system depending on the DEGs among different cell death subtypes (Huo et al, 2021).…”

“…Recently, some studies have explored the pyroptosis- or ferroptosis-related molecular subgrouping in various cancers, including PAAD, lung adenocarcinoma, and hepatocellular carcinoma ( Tang et al, 2020a ; Fu and Song, 2021 ; Liu et al, 2021 ). Some strengths could be noticed in our study.…”

Apoptosis-Related Signature Predicts Prognosis and Immune Microenvironment Infiltration in Lung Adenocarcinoma

“…According to the pathological type of LC, it can be divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), of which non-small cell lung cancer includes LUAD and lung squamous carcinoma (LUSC). Meanwhile, LUAD accounts for 85% of non-small cell lung cancer and 40% of all types and is the most common type of LC ( Denisenko et al, 2018 ; Liu L.-P. et al, 2021 ). With no symptoms in the early stages of LC, it is usually detected at an advanced stage that is not amenable to surgical treatment and has a poor prognosis.…”