AUTHOR=Lu Xiuqing , Yuan Qi , Zhang Chao , Wang Sifen , Wei Weidong 

TITLE=Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancer

JOURNAL=Frontiers in Oncology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1149193

DOI=10.3389/fonc.2023.1149193

ISSN=2234-943X

ABSTRACT=Due to tumour heterogeneity, some breast cancer patients still have a poor prognosis. Anoikis, as a special form of cell apoptosis, plays a crucial role in the occurrence and development of tumours. However, related studies on the prognostic patterns of anoikis-related genes (ARGs) in breast cancer have not been reported. Accordingly, we obtained 338 valid ARGs and investigated somatic mutations, GO enrichment analysis, mRNA expression levels and DNA methylation of these genes. Meanwhile, by performing LASSO Cox hazard regression analysis in TCGA-BRCA dataset, we established a prognostic signature composed of 6 OS related ARGs, defined as anoikis related index (ACI), which was verified in external cohorts (METABRIC and GSE96058). Subsequently, breast cancer patients were divided into two groups according to ACI level for follow-up study. Further analysis showed that, in all cohorts, patients in the high-ACI group had poorer overall survival (OS) than those in the low-ACI group, and the degree of clinical manifestation were more severe in high-ACI group patients. The optimal nomogram including ACI, age, PAM50 subtype and N stage was further constructed, and the discrimination was verified by calibration curve, decision curve analysis, and time dependent receiver operating characteristic (ROC) curve. Ultimately, we explored the potential impacts of anoikis on immune cells infiltrating tumors, immune checkpoints, growth factors, and cytokine levels. We further discussed the potential implications of anoikis in breast cancer immunotherapy and highlighted small molecule compounds that could offer therapeutic benefits. Based on our findings, it is clear that anoikis holds important prognostic value in breast cancer and offers a novel approach to managing patients with varying prognoses and implementing more precise immunotherapy.