scholarly journals Tumor Mutation Burden and Immune Invasion Characteristics in Triple Negative Breast Cancer: Genome High-Throughput Data Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chundi Gao ◽  
Huayao Li ◽  
Cun Liu ◽  
Xiaowei Xu ◽  
Jing Zhuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mutation Rate ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Cancer Genome ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Tumor Mutation Burden ◽  
Mutation Burden

In recent years, the emergence of immunotherapy has provided a new perspective for the treatment and management of triple-negative breast cancer (TNBC). However, the relationship between tumor mutation burden (TMB) and immune infiltration and the prognosis of TNBC remains unclear. In this study, to explore the immunogenicity of TNBC, we divided patients with TNBC into high and low TMB groups based on the somatic mutation data of TNBC in The Cancer Genome Atlas (TCGA), and screened out genes with mutation rate ≥10. Then, Kaplan-Meier survival analysis revealed that the 5-year survival rate of the high TMB group was much higher than that of the low TMB group and the two groups also showed differences in immune cell infiltration. Further exploration found that the FAT3 gene, which displays significant difference and a higher mutation rate between the two groups, is not only significantly related to the prognosis of TNBC patients but also exhibits difference in immune cell infiltration between the wild group and the mutant group of the FAT3 gene. The results of gene set enrichment analysis and drug sensitivity analysis further support the importance of the FAT3 gene in TNBC. This study reveals the characteristics of TMB and immune cell infiltration in triple-negative breast cancer and their relationship with prognosis, to provide new biomarkers and potential treatment options for the future treatment of TNBC. The FAT3 gene, as a risk predictor gene of TNBC, is considered a potential biological target and may provide new insight for the treatment of TNBC.

scholarly journals Rates of immune cell infiltration in patients with triple-negative breast cancer by molecular subtype

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0204513 ◽  
Author(s):  
Kenichi Harano ◽  
Ying Wang ◽  
Bora Lim ◽  
Robert S. Seitz ◽  
Stephan W. Morris ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Molecular Subtype ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

scholarly journals Classification of triple-negative breast cancer based on immune cell infiltration

2020 ◽  
Author(s):  
Wenji Shi ◽  
Dan Wang ◽  
Luz Angela Torres-de la Roche ◽  
Rui Zhuo ◽  
Rudy Leon De Wilde
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
B Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Immune Phenotype ◽  
Cluster A

Abstract Background Although the classification system of triple-negative breast cancer(TNBC) has become more and more perfect, there is no report on the immune subtype of triple-negative breast cancer based on immune cell infiltration. Results According to immune infiltrating cells, data from 360 patients were divided into cluster A (subtype 1 and subtype 3) and cluster B (subtype 2; with poorly immune phenotype). Expression of memory B cells, naïve B cells, M0 macrophages, M1 macrophages, CD4 memory activated T cells, and CD4 naïve T cells were significantly higher in cluster A (P < 0.05). In contrast, the expression of M2 macrophages and resting mast cells were higher in cluster B (P < 0.05). GSVA results show that B cell receptor pathway and JAK-STAT pathway are activated and more frequently altered in cluster A (P < 0.05). mTOR pathway alterations usually appear in cluster B (P < 0.05). Compared with cluster A, the risk of recurrence in cluster B patients is significantly increased (P < 0.05). Conclusions This analysis of tumor microenvironment revealed the multifaceted nature of TNBC and its impact on patient prognosis, being recurrence more often in those with poorly immune phenotype. These results provide a reference for further exploration of the heterogeneity of TNBC.

scholarly journals Association of Galectin 9 Expression with Immune Cell Infiltration, Programmed Cell Death Ligand-1 Expression, and Patient’s Clinical Outcome in Triple-Negative Breast Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1383
Author(s):  
Mi-Ha Ju ◽  
Kyung-Do Byun ◽  
Eun-Hwa Park ◽  
Jin-Hwa Lee ◽  
Song-Hee Han
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Clinical Outcome ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

Galectin-9 (Gal-9) is an immune checkpoint protein that facilitates T cell exhaustion and modulates the tumor-associated microenvironment, and could be a potential target for immune checkpoint inhibition. This study was conducted to assess Gal-9 expression in triple-negative breast cancer (TNBC) and evaluate its association with programmed cell death ligand 1 (PD-L1) expression and immune cell infiltration in tumors and the clinical outcome of patients. Overall, 109 patients with TNBC were included. Gal-9 expression was assessed its relationships with tumor clinicopathologic characteristics, tumor-infiltrating lymphocyte (TIL) levels, PD-L1+ immune cells, and tumor cells by tissue microarray and immunohistochemistry. Low Gal-9 expression was statistically correlated with higher tumor stage (p = 0.031) and presence of lymphovascular invasion (p = 0.008). High Gal-9 expression was associated with a high level of stromal TILs (sTIL; p = 0.011) and positive PD-L1 expression on tumor cells (p = 0.004). In survival analyses, low Gal-9 expression was associated with significantly poor OS (p = 0.013) in patients with TNBC with PD-L1 negativity in tumor cells. Our findings suggest that increased Gal-9 expression is associated with changes in the antitumor microenvironment, such as increased immune cell infiltration and antimetastatic changes. This study emphasizes the predictive value and promising clinical applications of Gal-9 in TNBC.

scholarly journals Association Between Tumor Mutation Burden and Prognosis in Lower-Grade Glioma: An Exploratory Study 

2021 ◽  
Author(s):  
Di Cao ◽  
Jun Wang ◽  
Yan Lin ◽  
Guangwei Li
Keyword(s):  
Immune Cell ◽  
Differential Expression Analysis ◽  
Cell Infiltration ◽  
Lower Grade ◽  
Immune Cell Infiltration ◽  
Hub Genes ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Lower Grade Glioma ◽  
Genome Atlas

Abstract Background: The therapeutic efficacy of immune checkpoint inhibitor therapy is highly influenced by tumor mutation burden (TMB). The relationship between TMB and prognosis in lower-grade glioma is still unclear. We aimed to explore the relationships and mechanisms between them in lower-grade glioma.Methods: We leveraged somatic mutation data from The Cancer Genome Atlas (TCGA). Clinical cases were divided into high- and low-TMB groups based on the median of TMB. Infiltrating immune cells were analyzed using CIBERSORT and differential expression analysis between the prognostic groups performed. The key genes were identified as intersecting between immune-related genes. Cox regression and survival analysis were performed on the intersecting genes. A total of 7 hub genes were identified. The effect of somatic copy number alterations (SCNA) of the hub genes on immune cell infiltration was analyzed using TIMER, which was used to determine the risk factors and immune infiltration status in LGG. Subsequently, based on hub genes, a TMB Prognosis Index (TMBPI) model was constructed to predict the risk in LGG patients. Besides, this model was validated using data from TCGA and Chinese Glioma Genome Atlas (CGGA).Results: High-TMB favored worse prognosis (P＜0.001) and macrophage infiltration was an independent risk factor (P＜0.001). In the high-TMB group (P=0.033, P=0.009), the proportion of macrophages M0 and M2 increased and monocytes decreased (P=0.006). Besides, the SCNA of the hub genes affected the level of immune cell infiltration by varying degrees among which IGF2BP3, NPNT, and PLA2G2A had a significant impact. The AUC of the ROC curve at 1-, 3- and 5-years were all above 0.74.Conclusions: This study implies that high-TMB correlated with unfavorable prognosis in lower-grade glioma. And high-TMB may have an impact on prognosis by changing tumor microenvironment, caused by the SCNAs of genes. The TMBPI model accurately predicted prognosis in LGG patients.

scholarly journals Molecular Characterization of the Clinical and Tumor Immune Microenvironment Signature of 5-methylcytosine-Related Regulators in non-small Cell Lung Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Taisheng Liu ◽  
Liyi Guo ◽  
Guihong Liu ◽  
Xiaoshan Hu ◽  
Xiaoning Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Check Point ◽  
Clinical Prognosis ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Immune Check Point Inhibitor

Background: DNA methylation is an important epigenetic modification, among which 5-methylcytosine methylation (5mC) is generally associated with tumorigenesis. Nonetheless, the potential roles of 5mC regulators in the tumor microenvironment (TME) remain unclear.Methods: The 5mC modification patterns of 1,374 lung adenocarcinoma samples were analyzed systematically. The correlation between the 5mC modification and tumor microenvironment cell infiltration was further assessed. The 5mCscore was developed to evaluate tumor mutation burden, immune check-point inhibitor response, and the clinical prognosis of individual tumors.Results: Three 5mC modification patterns were established based on the clinical characteristics of 21 5mC regulators. According to the differential expression of 5mC regulators, three distinct 5mC gene cluster were also identified, which showed distinct TME immune cell infiltration patterns and clinical prognoses. The 5mCscore was constructed to evaluate the tumor mutation burden, immune check-point inhibitor response, and prognosis characteristics. We found that patients with a low 5mCscore had significant immune cell infiltration and increased clinical benefit.Conclusion: This study indicated that the 5mC modification is involved in regulating TME infiltration remodeling. Targeting 5mC modification regulators might be a novel strategy to treat lung cancer.

scholarly journals Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Marcel Smid ◽  
F. Germán Rodríguez-González ◽  
Anieta M. Sieuwerts ◽  
Roberto Salgado ◽  
Wendy J. C. Prager-Van der Smissen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Cancer Genome ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Mutational Signatures
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