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 ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Chundi Gao ◽  
Huayao Li ◽  
Cun Liu ◽  
Xiaowei Xu ◽  
Jing Zhuang ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuomao Mo ◽  
Daiyuan Liu ◽  
Dade Rong ◽  
Shijun Zhang

Background: Generally, hepatocellular carcinoma (HCC) exists in an immunosuppressive microenvironment that promotes tumor evasion. Hypoxia can impact intercellular crosstalk in the tumor microenvironment. This study aimed to explore and elucidate the underlying relationship between hypoxia and immunotherapy in patients with HCC.Methods: HCC genomic and clinicopathological datasets were obtained from The Cancer Genome Atlas (TCGA-LIHC), Gene Expression Omnibus databases (GSE14520) and International Cancer Genome Consortium (ICGC-LIRI). The TCGA-LIHC cases were divided into clusters based on single sample gene set enrichment analysis and hierarchical clustering. After identifying patients with immunosuppressive microenvironment with different hypoxic conditions, correlations between immunological characteristics and hypoxia clusters were investigated. Subsequently, a hypoxia-associated score was established by differential expression, univariable Cox regression, and lasso regression analyses. The score was verified by survival and receiver operating characteristic curve analyses. The GSE14520 cohort was used to validate the findings of immune cell infiltration and immune checkpoints expression, while the ICGC-LIRI cohort was employed to verify the hypoxia-associated score.Results: We identified hypoxic patients with immunosuppressive HCC. This cluster exhibited higher immune cell infiltration and immune checkpoint expression in the TCGA cohort, while similar significant differences were observed in the GEO cohort. The hypoxia-associated score was composed of five genes (ephrin A3, dihydropyrimidinase like 4, solute carrier family 2 member 5, stanniocalcin 2, and lysyl oxidase). In both two cohorts, survival analysis revealed significant differences between the high-risk and low-risk groups. In addition, compared to other clinical parameters, the established score had the highest predictive performance at both 3 and 5 years in two cohorts.Conclusion: This study provides further evidence of the link between hypoxic signals in patients and immunosuppression in HCC. Defining hypoxia-associated HCC subtypes may help reveal potential regulatory mechanisms between hypoxia and the immunosuppressive microenvironment, and our hypoxia-associated score could exhibit potential implications for future predictive models.


2021 ◽  
Vol 11 ◽  
Author(s):  
Young-Sil An ◽  
Se-Hyuk Kim ◽  
Tae Hoon Roh ◽  
So Hyun Park ◽  
Tae-Gyu Kim ◽  
...  

BackgroundThe purpose of this study was to investigate the correlation between 18F-fluorodeoxyglucose (FDG) uptake and infiltrating immune cells in metastatic brain lesions.MethodsThis retrospective study included 34 patients with metastatic brain lesions who underwent brain 18F-FDG positron emission tomography (PET)/computed tomography (CT) followed by surgery. 18F-FDG uptake ratio was calculated by dividing the standardized uptake value (SUV) of the metastatic brain lesion by the contralateral normal white matter uptake value. We investigated the clinicopathological characteristics of the patients and analyzed the correlation between 18F-FDG uptake and infiltration of various immune cells. In addition, we evaluated immune-expression levels of glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and Ki-67 in metastatic brain lesions.ResultsThe degree of 18F-FDG uptake of metastatic brain lesions was not significantly correlated with clinical parameters. There was no significant relationship between the 18F-FDG uptake and degree of immune cell infiltration in brain metastasis. Furthermore, other markers, such as GLUT1, HK2, and Ki-67, were not correlated with degree of 18F-FDG uptake. In metastatic brain lesions that originated from breast cancer, a higher degree of 18F-FDG uptake was observed in those with high expression of CD68.ConclusionsIn metastatic brain lesions, the degree of 18F-FDG uptake was not significantly associated with infiltration of immune cells. The 18F-FDG uptake of metastatic brain lesions from breast cancer, however, might be associated with macrophage activity.


2014 ◽  
Vol 63 (4) ◽  
pp. 395-406 ◽  
Author(s):  
Shenyou Sun ◽  
Xiaochun Fei ◽  
Yan Mao ◽  
Xiumin Wang ◽  
David H. Garfield ◽  
...  

2017 ◽  
Vol 28 ◽  
pp. i15
Author(s):  
J. Budczies ◽  
B.V. Sinn ◽  
B.M. Pfitzner ◽  
S. Villegas-Angel ◽  
B. Ingold-Heppner ◽  
...  

2021 ◽  
Vol 10 (1) ◽  
pp. 261-272
Author(s):  
Zhi Wang ◽  
Di Wu ◽  
Menglu Dong ◽  
Yu Xia ◽  
Tao Xu

2021 ◽  
Author(s):  
Xiaoli Wang ◽  
Silu Xu ◽  
Lingli Huang ◽  
Lei Wang ◽  
Nan Wu

Abstract To identify molecular features related to immunogenic activity in breast cancer (BC) and provide new targets and directions for BC immunotherapy. We first used ESTIMATE to evaluate the degree of immune cell infiltration of the BC patients in TCGA and METABRIC, and explore the relationship between the degree of immune cell infiltration and prognosis of breast cancer patients. Then, we identified the cancer pathways, proteins, miRNAs related to BC immunogenicity, and predicted miRNAs target genes and identified the pathways related to target genes with KEGG pathway enrichment analysis. We also explored the correlation between PD-L1 expression level and cancer pathways and found that PD-L1 expression showed a positive association with cancer pathways. In this article we have successfully identified several cancer pathways, proteins, miRNAs and their target genes, which could be as promising new target for BC immunotherapy. And PD-L1 blockade therapy may be more effective in BC patients with the activation of some cancer pathways.


Sign in / Sign up

Export Citation Format

Share Document