Exploration of prognosis and immunometabolism landscapes in ER+ breast cancer based on a novel lipid metabolism-related signature

Frontiers in Immunology

Immunology

Jun Zhou¹  Jiaxin Li²  Jianming Hu²  Wuzhen Chen²  Chao Ni²  Huanhuan Huang²  Yao Yao²  Lesang Shen²  Fengbo Huang³ 

[1] Department of Breast Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University, Hangzhou, Zhejiang, China;Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China;Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China;Cancer Center, Zhejiang University, Hangzhou, China;Department of Pathology, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China;

关键词: lipid metabolism;    estrogen receptor-positive breast cancer;    prognostic signature;    tumor immune microenvironment;    therapy response;   

DOI  :  10.3389/fimmu.2023.1199465

 received in 2023-04-03, accepted in 2023-06-19,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionLipid metabolic reprogramming is gaining attention as a hallmark of cancers. Recent mounting evidence indicates that the malignant behavior of breast cancer (BC) is closely related to lipid metabolism. Here, we focus on the estrogen receptor-positive (ER+) subtype, the most common subgroup of BC, to explore immunometabolism landscapes and prognostic significance according to lipid metabolism-related genes (LMRGs).MethodsSamples from The Cancer Genome Atlas (TCGA) database were used as training cohort, and samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), Gene Expression Omnibus (GEO) datasets and our cohort were applied for external validation. The survival-related LMRG molecular pattern and signature were constructed by unsupervised consensus clustering and least absolute shrinkage and selection operator (LASSO) analysis. A lipid metabolism-related clinicopathologic nomogram was established. Gene enrichment and pathway analysis were performed to explore the underlying mechanism. Immune landscapes, immunotherapy and chemotherapy response were further explored. Moreover, the relationship between gene expression and clinicopathological features was assessed by immunohistochemistry.ResultsTwo LMRG molecular patterns were identified and associated with distinct prognoses and immune cell infiltration. Next, a prognostic signature based on nine survival-related LMRGs was established and validated. The signature was confirmed to be an independent prognostic factor and an optimal nomogram incorporating age and T stage (AUC of 5-year overall survival: 0.778). Pathway enrichment analysis revealed differences in immune activities, lipid biosynthesis and drug metabolism by comparing groups with low- and high-risk scores. Further exploration verified different immune microenvironment profiles, immune checkpoint expression, and sensitivity to immunotherapy and chemotherapy between the two groups. Finally, arachidonate 15-lipoxygenase (ALOX15) was selected as the most prominent differentially expressed gene between the two groups. Its expression was positively related to larger tumor size, more advanced tumor stage and vascular invasion in our cohort (n = 149).DiscussionThis is the first lipid metabolism-based signature with value for prognosis prediction and immunotherapy or chemotherapy guidance for ER+ BC.

【 授权许可】

Unknown   
Copyright © 2023 Shen, Huang, Li, Chen, Yao, Hu, Zhou, Huang and Ni