Abstract

Objective To investigate the expression patterns and prognostic characteristics of inflammasome-related genes (IRGs) across cancer types and develop a robust biomarker for the prognosis of KIRC. Methods The differentially expressed IRGs and prognostic genes among 10 cancers were analyzed based on The Cancer Genome Atlas (TCGA) dataset. Subsequently, an IRGs risk signature was developed in KIRC. Its prognostic accuracy was evaluated by receiver operating characteristic (ROC) analysis. The independent predictive capacity was identified by stratification survival and multivariate Cox analyses. The gene ontology (GO) analysis and principal component analysis (PCA) were performed to explore biological functions of the IRGs signature in KIRC. Results The expression patterns and prognostic association of IRGs varied from different cancers, while KIRC showed the most abundant survival-related dysregulated IRGs. The IRG signature for KIRC was able to independently predict survival, and the signature genes were mainly involved inimmune-related processes. Conclusions The pan-cancer analysis provided a comprehensive landscape of IRGs across cancer types and identified a strong association between IRGs and the prognosis of KIRC. Further IRGs signature represented a reliable prognostic predictor for KIRC and verified the prognostic value of inflammasomes in KIRC, contributing to our understanding of therapies targeting inflammasomes for human cancers.

Highlights

  • Inflammasomes are a kind of intracellular innate immune multiprotein complexes, the concept of which was introduced by Martinon in 2002 [1]

  • A total of 40 genes were included in the inflammasome-related gene set: 20 of them were retrieved from the gene set (REACTOME_INFLAMMASOMES, M1072) in the Molecular Signatures Database v7.0 [19, 20], while the added genes were described as the components of inflammasome complexes or being involved in the inflammasome-related pathways according to the published literature

  • To ensure the stability of differential analysis and survival analysis, we only selected 10 types of cancer containing more than 20 normal samples and 20 dead samples. e cancer types included colon adenocarcinoma (COAD), liver hepatocellular carcinoma (LIHC), breast invasive carcinoma (BRCA), head and neck squamous cell carcinoma (HNSC), lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), kidney renal papillary cell carcinoma (KIRP), Kidney renal clear cell carcinoma (KIRC), stomach adenocarcinoma (STAD), and uterine corpus endometrial carcinoma (UCEC)

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Summary

Introduction

Inflammasomes are a kind of intracellular innate immune multiprotein complexes, the concept of which was introduced by Martinon in 2002 [1]. Inflammasomes consist of three components: sensor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)/ PYCARD, and pro-caspase-1. Inflammasomes can be activated by recognizing pathogen-associated and damage-associated molecular patterns (PAMPs and DAMPs) via their sensor protein, inducing the activation of pro-caspase-1. Studies have shown that inflammasomes play essential roles in regulating the physiological and pathological processes and correlate with various human diseases such as type 2 diabetes [3], immune-related diseases [4], and tumor [5].

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