Abstract
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.
Highlights
Breast cancer (BC) is becoming the most commonly diagnosed cancer in women worldwide, and it is estimated that approximately 2.3 million new cases (11.7%) have been diagnosed in 2020 [1]
We extracted RNA-seq transcriptome data and clinical characteristics of BC from The Cancer Genome Atlas (TCGA) database and conducted the immune computational methods, such as ESTIMATE and CIBERSORT, to screen differentially expressed gene (DEG) which was related to immune component and clinical outcome
inducible T-cell kinase (ITK), CD3E, CCL19, CD2, SH2D1A, CD5, SLAMF6, and SPN, were obtained, and we conducted further analysis, including survival and clinicopathological characteristics correlation analysis, GSEA, and correlation with tumor-infiltrating immune cell (TIC) focused on ITK
Summary
Breast cancer (BC) is becoming the most commonly diagnosed cancer in women worldwide, and it is estimated that approximately 2.3 million new cases (11.7%) have been diagnosed in 2020 [1]. Increasing evidence indicates a strong association between TME and tumorigenesis, cancer cell proliferation, invasion, and metastasis [5]. This connection demonstrates a promising target that could be utilized for cancer therapy. By combining the analysis of transcriptome and clinical data from TCGA, we established immune and stromal scores, which allowed us to screen precisely for prognostic DEGs. Thereafter, through the bioinformatics analyses, eight genes were considered key genes for BC patients, from which a novel gene, ITK, presented great predictive value in terms of the OS and clinical outcomes of BC patients. The tumor microenvironment (TME), consisting of blood vessels, immune cells, fibroblasts, and extracellular matrix, plays a pivotal role in tumorigenesis and progression. We still lack a deep understanding of the correlation between tumor invasion and TME status
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