Abstract

Sarcoma is a rare and an extremely aggressive form of cancer that originates from mesenchymal cells. Pyroptosis exerts a dual effect on tumours by inhibiting tumour cell proliferation while creating a microenvironment suitable for tumour cell development and proliferation. However, the significance of pyroptosis-related gene (PRG) expression in sarcoma has not yet been evaluated. Here, we conduct a retrospective analysis to examine PRG expression in 256 sarcoma samples from The Cancer Genome Atlas database. We identified the PRGs that had a significant correlation with overall patient survival in sarcoma by performing a univariate Cox regression analysis. Subsequently, we conducted a LASSO regression analysis and created a risk model for a six-PRG signature. As indicated from the Kaplan–Meier analysis, this signature revealed a significant difference between high- and low-risk sarcoma patients. A receiver operating characteristic curve analysis confirmed that this signature could predict overall patient survival in sarcoma patients with high sensitivity and specificity. Gene ontology annotation and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses revealed that five independent PRGs were closely associated with increased immune activity. Moreover, we also deciphered that increased number of immune cells infiltrated the tumour microenvironment in sarcoma. In brief, the PRG signature can effectively act as novel prognostic biomarker for sarcoma patients and is associated with the tumour immune microenvironment.

Highlights

  • Sarcomas are a heterogeneous group of uncommon mesenchymal malignancies that originate from the mesodermal tissue

  • As a result, identifying novel prognostic biomarkers for accurate prognostic evaluation of sarcoma patients and the development of potential targeted treatments is of great significance

  • This study is aimed at building a risk-score model to predict patient prognoses by conducting retrospective bioinformatic analysis of pyroptosis-related gene (PRG) expression profiles in sarcoma patients

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Summary

Introduction

Sarcomas are a heterogeneous group of uncommon mesenchymal malignancies that originate from the mesodermal tissue. They amount to approximately 1–2% of all malignancies, with 4-6 estimated incidence of sarcoma per 100,000 cases of cancer per year [1]. Since current systemic therapy options have limited effectiveness, metastatic progression is observed in approximately 50% of sarcoma patients during the first five years of treatment [3]. Pretreatment assessment of sarcomas by molecular biomarkers potentially facilitates the development of a risk-adapted approach for individualized treatment strategies in the future [5]. As a result, identifying novel prognostic biomarkers for accurate prognostic evaluation of sarcoma patients and the development of potential targeted treatments is of great significance

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