A Novel Immune and Stroma Related Prognostic Marker for Invasive Breast Cancer in Tumor Microenvironment: A TCGA Based Study

BackgroundBreast cancer (BC) is the most frequent cancer in women. The tumor microenvironment (TME), consisting of blood vessels, immune cells, fibroblasts, and extracellular matrix, plays a pivotal role in tumorigenesis and progression. Increasing evidence has emphasized the importance of TME, espe...

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Autores principales: Yizhou Huang, Lizhi Chen, Ziyi Tang, Yu Min, Wanli Yu, Gangyi Yang, Lili Zhang
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Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:5d2b979627c745e0b289c05ce85394b42021-11-18T06:39:24ZA Novel Immune and Stroma Related Prognostic Marker for Invasive Breast Cancer in Tumor Microenvironment: A TCGA Based Study1664-239210.3389/fendo.2021.774244https://doaj.org/article/5d2b979627c745e0b289c05ce85394b42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.774244/fullhttps://doaj.org/toc/1664-2392BackgroundBreast cancer (BC) is the most frequent cancer in women. The tumor microenvironment (TME), consisting of blood vessels, immune cells, fibroblasts, and extracellular matrix, plays a pivotal role in tumorigenesis and progression. Increasing evidence has emphasized the importance of TME, especially the immune components, in patients with BC. Nevertheless, we still lack a deep understanding of the correlation between tumor invasion and TME status.MethodsTranscriptome and clinical data were retrieved from The Cancer Genome Atlas (TCGA) database. ESTIMATE algorithm was applied for quantifying stromal and immune scores. Then we screened out the differentially expressed genes (DEGs) through the intersection analysis. Furthermore, the establishment of protein-protein interaction (PPI) network and univariate COX regression analysis were utilized to determine the core genes in DEGs. In addition, we also performed Gene Set Enrichment Analysis (GSEA) and CIBERSORT analysis to distinguish the function of crucial gene expression and the proportion of tumor-infiltrating immune cells (TICs), respectively.ResultsA total of 1178 samples (112 normal samples and 1066 tumor samples) were extracted from TCGA for calculation, and 226 DEGs were obtained from this assessment. Further intersection analysis revealed eight key genes, including ITK, CD3E, CCL19, CD2, SH2D1A, CD5, SLAMF6, SPN, which were proven to correlate with BC status. Moreover, ITK was picked out for further study. The results illustrated that high expression of BC patients had a more prolonged overall survival (OS) time than ITK low expression BC patients (p = 0.009), and ITK expression also presented the statistical significance in age, TNM staging, tumor size classification, and metastasis classification. Additionally, GSEA and CIBERSORT analysis indicated that ITK expression had an association with immune activity in TME.ConclusionITK may be a potential indicator for prognosis prediction in patients with BC, and its biological behavior may promote our understanding of the molecular mechanism of tumor progression and targeted therapy.Yizhou HuangLizhi ChenZiyi TangYu MinWanli YuGangyi YangLili ZhangFrontiers Media S.A.articlebreast cancertumor microenvironmentTCGAtumor-infiltrating immune cellsITKDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic breast cancer
tumor microenvironment
TCGA
tumor-infiltrating immune cells
ITK
Diseases of the endocrine glands. Clinical endocrinology
RC648-665
spellingShingle breast cancer
tumor microenvironment
TCGA
tumor-infiltrating immune cells
ITK
Diseases of the endocrine glands. Clinical endocrinology
RC648-665
Yizhou Huang
Lizhi Chen
Ziyi Tang
Yu Min
Wanli Yu
Gangyi Yang
Lili Zhang
A Novel Immune and Stroma Related Prognostic Marker for Invasive Breast Cancer in Tumor Microenvironment: A TCGA Based Study
description BackgroundBreast cancer (BC) is the most frequent cancer in women. The tumor microenvironment (TME), consisting of blood vessels, immune cells, fibroblasts, and extracellular matrix, plays a pivotal role in tumorigenesis and progression. Increasing evidence has emphasized the importance of TME, especially the immune components, in patients with BC. Nevertheless, we still lack a deep understanding of the correlation between tumor invasion and TME status.MethodsTranscriptome and clinical data were retrieved from The Cancer Genome Atlas (TCGA) database. ESTIMATE algorithm was applied for quantifying stromal and immune scores. Then we screened out the differentially expressed genes (DEGs) through the intersection analysis. Furthermore, the establishment of protein-protein interaction (PPI) network and univariate COX regression analysis were utilized to determine the core genes in DEGs. In addition, we also performed Gene Set Enrichment Analysis (GSEA) and CIBERSORT analysis to distinguish the function of crucial gene expression and the proportion of tumor-infiltrating immune cells (TICs), respectively.ResultsA total of 1178 samples (112 normal samples and 1066 tumor samples) were extracted from TCGA for calculation, and 226 DEGs were obtained from this assessment. Further intersection analysis revealed eight key genes, including ITK, CD3E, CCL19, CD2, SH2D1A, CD5, SLAMF6, SPN, which were proven to correlate with BC status. Moreover, ITK was picked out for further study. The results illustrated that high expression of BC patients had a more prolonged overall survival (OS) time than ITK low expression BC patients (p = 0.009), and ITK expression also presented the statistical significance in age, TNM staging, tumor size classification, and metastasis classification. Additionally, GSEA and CIBERSORT analysis indicated that ITK expression had an association with immune activity in TME.ConclusionITK may be a potential indicator for prognosis prediction in patients with BC, and its biological behavior may promote our understanding of the molecular mechanism of tumor progression and targeted therapy.
format article
author Yizhou Huang
Lizhi Chen
Ziyi Tang
Yu Min
Wanli Yu
Gangyi Yang
Lili Zhang
author_facet Yizhou Huang
Lizhi Chen
Ziyi Tang
Yu Min
Wanli Yu
Gangyi Yang
Lili Zhang
author_sort Yizhou Huang
title A Novel Immune and Stroma Related Prognostic Marker for Invasive Breast Cancer in Tumor Microenvironment: A TCGA Based Study
title_short A Novel Immune and Stroma Related Prognostic Marker for Invasive Breast Cancer in Tumor Microenvironment: A TCGA Based Study
title_full A Novel Immune and Stroma Related Prognostic Marker for Invasive Breast Cancer in Tumor Microenvironment: A TCGA Based Study
title_fullStr A Novel Immune and Stroma Related Prognostic Marker for Invasive Breast Cancer in Tumor Microenvironment: A TCGA Based Study
title_full_unstemmed A Novel Immune and Stroma Related Prognostic Marker for Invasive Breast Cancer in Tumor Microenvironment: A TCGA Based Study
title_sort novel immune and stroma related prognostic marker for invasive breast cancer in tumor microenvironment: a tcga based study
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/5d2b979627c745e0b289c05ce85394b4
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