A novel pyroptosis-associated gene signature for immune status and prognosis of cutaneous melanoma.

Zhengyuan Wu,Xingqun Zhang,Leilei Chen,Yi Yao,Chaojie Jin,Jing Xu

doi:10.7717/peerj.12304

Abstract

BackgroundCutaneous melanoma (CM) is a life-threatening destructive malignancy. Pyroptosis significantly correlates with programmed tumor cell death and its microenvironment through active host-tumor crosstalk. However, the prognostic value of pyroptosis-associated gene signatures in CM remains unclear.MethodsGene profiles and clinical data of patients with CM were downloaded from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes associated with pyroptosis and overall survival (OS). We constructed a prognostic gene signature using LASSO analysis, then applied immune cell infiltration scores and Kaplan-Meier, Cox, and pathway enrichment analyses to determine the roles of the gene signature in CM. A validation cohort was collected from the Gene Expression Omnibus (GEO) database.ResultsFour pyroptosis-associated genes were identified and incorporated into a prognostic gene signature. Integrated bioinformatics findings showed that the signature correlated with patient survival and was associated with tumor growth and metastasis. The results of Gene Set Enrichment Analysis of a risk signature indicated that several enriched pathways are associated with cancer and immunity. The risk signature for immune status significantly correlated with tumor stem cells, the immune microenvironment, immune cell infiltration and immune subtypes. The expression of four pyroptosis genes significantly correlated with the OS of patients with CM and was related to the sensitivity of cancer cells to several antitumor drugs. A signature comprising four genes associated with pyroptosis offers a novel approach to the prognosis and survival of patients with CM and will facilitate the development of individualized therapy.

Highlights

Cutaneous melanoma (CM) is a destructive malignancy that threatens human health (Ekwueme et al, 2011)
Univariate Cox analysis of the candidate Differentially expressed genes (DEGs) verified their association with prognosis (Fig. 2C), and correlation analysis showed that they were connected to each other (Fig. 2D)
We analyzed whether immune status, tumor microenvironment, immune components, tumor stemness, and chemotherapeutic drug sensitivity corresponded to the gene signature and pyroptosis genes, and found that our risk signature conferred advantages compared with those described above

Summary

Introduction

Cutaneous melanoma (CM) is a destructive malignancy that threatens human health (Ekwueme et al, 2011). A novel pyroptosis-associated gene signature for immune status and prognosis of cutaneous melanoma. Methods: Gene profiles and clinical data of patients with CM were downloaded from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes associated with pyroptosis and overall survival (OS). Results: Four pyroptosis-associated genes were identified and incorporated into a prognostic gene signature. The expression of four pyroptosis genes significantly correlated with the OS of patients with CM and was related to the sensitivity of cancer cells to several antitumor drugs. A signature comprising four genes associated with pyroptosis offers a novel approach to the prognosis and survival of patients with CM and will facilitate the development of individualized therapy

Methods

Results

Discussion

Conclusion