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

BackgroundTumor heterogeneity is widely recognized as a crucial factor impacting the prognosis of breast cancer (BC) patients. However, there remains an insufficient understanding of the underlying impact of anoikis on the prognosis of BC patients.MethodsThe researchers utilized the TCGA-BRCA datase...

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Main Authors: Xiuqing Lu, Qi Yuan, Chao Zhang, Sifen Wang, Weidong Wei
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2023.1149193/full
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author Xiuqing Lu
Qi Yuan
Chao Zhang
Sifen Wang
Weidong Wei
author_facet Xiuqing Lu
Qi Yuan
Chao Zhang
Sifen Wang
Weidong Wei
author_sort Xiuqing Lu
collection DOAJ
description BackgroundTumor heterogeneity is widely recognized as a crucial factor impacting the prognosis of breast cancer (BC) patients. However, there remains an insufficient understanding of the underlying impact of anoikis on the prognosis of BC patients.MethodsThe researchers utilized the TCGA-BRCA dataset to screen and analyze the differentially expressed genes of anoikis-related genes (ARGs) in BC and normal breast tissue. Prognostic gene signatures were established through univariate, LASSO, and multivariate Cox regression analyses. These signatures were evaluated using Kaplan-Meier curve and receiver operating characteristic (ROC) analyses, resulting in the development of an anoikis-related index (ACI). The training dataset was TCGA-BRCA, while METABRIC and GSE96058 were used for external validation. Additionally, nomograms were developed by combining risk scores and clinical parameters, enabling gene set enrichment analysis (GSEA) and tumor immunoassay. Furthermore, an exploration of small molecule compounds was conducted to identify potential therapeutic benefits.ResultsA six-gene anoikis-related signature was constructed, which divided BC patients into high- and low-ACI groups based on median ACI scores. The ACI accurately predicted prognosis and acted as an independent prognostic factor for BC patients. Patients in the high-ACI group exhibited poorer overall survival (OS) across all cohorts and showed more severe clinical manifestations compared to the low-ACI group. The study also explored the potential impacts of anoikis on immune cells infiltrating tumors, immune checkpoints, growth factors, and cytokine levels. Additionally, the potential implications of anoikis in BC immunotherapy were discussed, along with highlighting small molecule compounds that could offer therapeutic benefits.ConclusionsAnoikis was found to hold significant prognostic value in breast cancer, providing a novel approach for managing patients with different prognoses and implementing more precise immunotherapy strategies.
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spelling doaj.art-acfbf27f0d9e4bf88533c3aa8d14060c2023-07-04T18:12:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-07-011310.3389/fonc.2023.11491931149193Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancerXiuqing Lu0Qi Yuan1Chao Zhang2Sifen Wang3Weidong Wei4Department of Breast Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Breast Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Breast Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaBackgroundTumor heterogeneity is widely recognized as a crucial factor impacting the prognosis of breast cancer (BC) patients. However, there remains an insufficient understanding of the underlying impact of anoikis on the prognosis of BC patients.MethodsThe researchers utilized the TCGA-BRCA dataset to screen and analyze the differentially expressed genes of anoikis-related genes (ARGs) in BC and normal breast tissue. Prognostic gene signatures were established through univariate, LASSO, and multivariate Cox regression analyses. These signatures were evaluated using Kaplan-Meier curve and receiver operating characteristic (ROC) analyses, resulting in the development of an anoikis-related index (ACI). The training dataset was TCGA-BRCA, while METABRIC and GSE96058 were used for external validation. Additionally, nomograms were developed by combining risk scores and clinical parameters, enabling gene set enrichment analysis (GSEA) and tumor immunoassay. Furthermore, an exploration of small molecule compounds was conducted to identify potential therapeutic benefits.ResultsA six-gene anoikis-related signature was constructed, which divided BC patients into high- and low-ACI groups based on median ACI scores. The ACI accurately predicted prognosis and acted as an independent prognostic factor for BC patients. Patients in the high-ACI group exhibited poorer overall survival (OS) across all cohorts and showed more severe clinical manifestations compared to the low-ACI group. The study also explored the potential impacts of anoikis on immune cells infiltrating tumors, immune checkpoints, growth factors, and cytokine levels. Additionally, the potential implications of anoikis in BC immunotherapy were discussed, along with highlighting small molecule compounds that could offer therapeutic benefits.ConclusionsAnoikis was found to hold significant prognostic value in breast cancer, providing a novel approach for managing patients with different prognoses and implementing more precise immunotherapy strategies. https://www.frontiersin.org/articles/10.3389/fonc.2023.1149193/fullanoikisbreast cancerprognosisimmune infiltratesimmunotherapy
spellingShingle Xiuqing Lu
Qi Yuan
Chao Zhang
Sifen Wang
Weidong Wei
Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancer
Frontiers in Oncology
anoikis
breast cancer
prognosis
immune infiltrates
immunotherapy
title Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancer
title_full Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancer
title_fullStr Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancer
title_full_unstemmed Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancer
title_short Predicting the immune microenvironment and prognosis with a anoikis - related signature in breast cancer
title_sort predicting the immune microenvironment and prognosis with a anoikis related signature in breast cancer
topic anoikis
breast cancer
prognosis
immune infiltrates
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fonc.2023.1149193/full
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