|Table of Contents|

To construct a prognostic model and analyze the immune microenvironment of adrenocortical carcinoma based on pyroptosis gene

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 08
Page:
1496-1506
Research Field:
Publishing date:

Info

Title:
To construct a prognostic model and analyze the immune microenvironment of adrenocortical carcinoma based on pyroptosis gene
Author(s):
KONG Lingqi1; LI Kunfang2; DING Yi2; ZHANG Juanning2; MENG Xintong2; SUN Qirui2; QU Yanlin2
1.Department of Pediatric Surgery,Jining No.1 People's Hospital,Shandong Jining 272000,China;2.Basic Medical College，Jining Medical College,Shandong Jining 272067,China.
Keywords:
adrenal cortical carcinoma; pyroptosis; risk model; prognosis; immune microenvironment
PACS:
R736.6
DOI:
10.3969/j.issn.1672-4992.2024.08.023
Abstract:
Objective:A prognostic model of adrenal cortical carcinoma associated with pyroptosis gene was established,and its immune microenvironment was analyzed and verified by experiment.Methods：TCGA database and GTEx database were used to screen the differentially expressed genes related to pyroptosis.The prognostic risk model of ACC was constructed by Cox regression analysis and Lasso analysis.The prognostic value and clinical correlation relevance were explored based on the model and verified by external cohort.The differentially expressed genes were enriched by Go-KEGG and GSEA enrichment analysis,and the related carcinogenic pathways were explored.ssGSEA algorithm and Pearson correlation analysis were used to study the immune microenvironment of ACC.Real-time fluorescence quantification and immunohistochemical experiments verified the prediction results.Results：The ACC risk model was successfully constructed by Lasso analysis.Cox multivariate regression analysis showed that the risk score could be used as an independent prognostic factor to evaluate the prognosis.High-risk patients had lower OS and PFI,and the area under curve (AUC) of the time-dependent ROC curve was greater than 0.5.The risk model was also correlated with T,M and N clinical stages.The same risk grouping for the external cohort also showed a worse prognosis for high-risk patients,further confirming the universality of the risk model.Enrichment analysis showed that E2f,MYC and other oncogenic pathways were significantly up-regulated.In the high-risk group,the infiltration of most immune cells was poor,and the secretion of MHC molecules and chemokines was decreased,which was not conducive to the formation of anti-cancer immune microenvironment.TP53 and DNNB1 proteins were suggested as potential therapeutic targets for ACC.Real-time fluorescence quantification and immunohistochemical experiments verified the universality of the model.Conclusion：In this study,the risk model of adrenocortical carcinoma was successfully constructed by using bioinformatics method,which was well verified externally and had relatively accurate prognostic ability.Immune microenvironment analysis showed that ACC patients were often immunosuppressed,resulting in poor efficacy of popular immune checkpoint inhibitors.The expression of TP53 and DNNB1 oncoproteins is significant in high-risk patients,which can be used as potential therapeutic targets to improve the failure of immunotherapy.It is hoped that this risk model can provide a new idea for the prognostic identification and targeted therapy of adrenocortical carcinoma.

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Memo

Memo:
济宁市第一人民医院2022年度第一批“启航”科研项目（面上项目）(编号：2022QHM-018）
Last Update: 1900-01-01