A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer

Frontiers in Pharmacology

Pharmacology

Renhong Huang¹  Han Wang¹  Jin Hong¹ 

[1] Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;

关键词: senescence-associated genes;    triple-negative breast cancer;    modification patterns;    tumor immune microenvironment;    FAM3B;   

DOI  :  10.3389/fphar.2023.1191910

 received in 2023-03-22, accepted in 2023-04-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Recent studies have found that senescence-associated genes play a significant role in cancer biological processes. We aimed to analyze the characteristics and role of senescence-associated genes in triple-negative breast cancer (TNBC).Methods: We systematically screened senescence-associated secretory phenotype (SASP) genes based on the gene expression information in the TCGA database. According to the expression levels of senescence-associated genes, TNBC was classified into two subtypes, namely, TNBCSASP1 and TNBCSASP2, using an unsupervised cluster algorithm. We then performed gene expression, enrichment pathway, immune infiltration, mutational profile characterization, drug sensitivity and prognostic value analyses for the two subtypes. The reliability and prognostic predictive utility of this classification model were validated. The most prognostically relevant gene, FAM3B, was comprehensively identified and validated by tissue microarray in TNBC.Results: TNBC was classified into two senescence-associated subtypes, TNBCSASP1 and TNBCSASP2, based on the set of senescence-associated secretory phenotype genes, among which the TNBCSASP1 subtype had a poor prognosis. The TNBCSASP1 subtype was immunosuppressed, with suppressed immune-related signaling pathways and low immune cell infiltration. The effect of the mutation on the TP53 and TGF-β pathways could be related to the poor prognosis of the TNBCSASP1 subtype. Drug sensitivity analysis showed that AMG.706, CCT007093, and CHIR.99021 were potential targeted drugs for the TNBCSASP1 subtype. Finally, FAM3B was a key biomarker affecting the prognosis of patients with triple-negative breast cancer. Compared to normal breast tissue, the expression of FAM3B was reduced in triple-negative breast cancer. Survival analysis showed that overall survival was significantly shorter in triple-negative breast cancer patients with high FAM3B expression.Conclusion: A senescence-associated signature with different modification patterns has critical potential for providing a better understanding of TNBC biological processes, and FAM3B might serve as an applicable target for TNBC therapy.

【 授权许可】

Unknown   
Copyright © 2023 Huang, Wang, Hong, Wang, Wu, Huang, He, Chen, Li, Chen and Shen.