scholarly journals Expression Patterns of Immune Checkpoints in Breast Cancer Patients

2021 ◽  
Author(s):  
Dan Qiu ◽  
Xianxin Yan ◽  
Guijuan Zhang ◽  
Xinqin Xiao ◽  
Jingyu Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Checkpoint Inhibitors ◽  
Expression Patterns ◽  
Microarray Dataset ◽  
Tissue Expression ◽  
Immune Checkpoints ◽  
Rna Seq ◽  
Breast Cancer Patients ◽  
Insight Into ◽  
Mcf 7

Abstract Background: immunotherapy with immune checkpoint inhibitors (ICIs) for solid tumors had significantly improved overall survival (OS). Positive response to PD-1/PD-L1 blockades was observed in the treatment of solidtumors. Breast cancer (BC) patients are no exception. However, the efficacy of immunocheckpoint therapy in BC patients remains poor. A particularly important factor is the lack of studies on the expression patterns of immune checkpoints in BC patients. Method: in this study, the microarray dataset GSE10810 was downloaded from the Gene Expression Database Synthesis (GEO) to analyze the differential expression of BC genes and perform GO and KEGG analysis. Then, we explored theprognostic value of ICs for BC patients by analyzing RNA-seq and mutation data from 657 BC patients from theCancer Genome Atlas (TCGA) database. Next, we analyzed the differences in the expression of relevant immune checkpoints between 1085 BC patients and 291 healthy controls (HC) in the Genotype-Tissue Expression (GTEx) database. Finally, we analyzed the expression levels of IFNγ-R, PD-L1, STAT1, IDO and other genes in MCF-10A, MF-10AT, MCF-7, MDA-MB-231 cell lines.Results: It was found that increased expression of PD-1, PD-L1, STAT1, CTLA-4 was associated with poor OS in BC patients. In addition, co-expression of PD-L1 with PD-1, STAT1or CTLA-4 and co-expression of PD-1 with CTLA-4was related to poor OS. We analyzed associations between the proportionate expression of PD-L1 and PD-1, PD-L1 and STAT1, PD-1 and CTLA-4, PD-1 and LAG3, PD-L1 and CTLA-4 in BC patients, there was significance in correlation in both of the BC patients.The expression of STAT1 in BC patients was compared with that of HC, and it was found that STAT1 was highly expressed in BC patients. Conclusions: our results suggest that transcriptome-based co-expression of STAT1 and PD-L1 is a predictor for poor OS in BC patients, which might provide novel insight into designing combinational targeted therapy for BC.

scholarly journals Expression Patterns of Immune Checkpoints In Breast Cancer Patients

2021 ◽  
Author(s):  
Dan Qiu ◽  
Xianxin Yan ◽  
Guijuan Zhang ◽  
Xinqin Xiao ◽  
Jingyu Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Solid Tumors ◽  
Immune Checkpoint Inhibitors ◽  
Positive Response ◽  
Checkpoint Inhibitors ◽  
Expression Patterns ◽  
Immune Checkpoints ◽  
Breast Cancer Patients ◽  
Insight Into

Abstract Background: immunotherapy with immune checkpoint inhibitors (ICIs) for solid tumors had significantly improved overall survival (OS). Positive response to PD-1/PD-L1 blockades was observed in the treatment of solid tumors. Breast cancer (BC) patients are no exception. However, the efficacy of immunocheckpoint therapy in BC patients remains poor. A particularly important factor is the lack of studies on the expression patterns of immune checkpoints in BC patients. Results: It was found that increased expression of PD-1, PD-L1, STAT1, CTLA-4 was associated with poor OS in BC patients. In addition, co-expression of PD-L1 with PD-1, STAT1or CTLA-4 and co-expression of PD-1 with CTLA-4was related to poor OS. We analyzed associations between the proportionate expression of PD-L1 and PD-1, PD-L1 and STAT1, PD-1 and CTLA-4, PD-1 and LAG3, PD-L1 and CTLA-4 in BC patients, there was significance in correlation in both of the BC patients. The expression of STAT1 in BC patients was compared with that of HC, and it was found that STAT1 was highly expressed in BC patients. Conclusions: our results suggest that transcriptome-based co-expression of STAT1 and PD-L1 is a predictor for poor OS in BC patients, which might provide novel insight into designing combinational targeted therapy for BC.

scholarly journals Checkpoint Inhibitors in Breast Cancer - Current Status and Future Directions

Breast Care ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Joachim Bischoff
Keyword(s):  
Breast Cancer ◽  
T Cell Activation ◽  
Cell Activation ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Death Receptor ◽  
Target Population ◽  
Current Status ◽  
Immune Checkpoints ◽  
Breast Cancer Patients

Antineoplastic agents directly targeting tumor cells have represented the major strategy of systemic anticancer therapy for many years. Nevertheless, overcoming resistance mechanisms remains a great challenge because treatment options are limited in many cases. From this point of view, immunotherapeutic approaches seem promising in a broad spectrum of solid tumors. These include in particular the currently available inhibitors directed against immune checkpoints leading to a significant T-cell activation. To date, the programmed death receptor 1 (PD-1) and its ligand are the most prominent targets in this context. However, the role of checkpoint inhibitors in the treatment of breast cancer is still being debated, and the main focus is on triple-negative breast cancer patients as a target population in many ongoing trials. Moreover, the potential superiority of combinations with other anticancer drugs such as cytotoxics and targeted agents will be discussed.

scholarly journals Genome-Wide Investigation of Genes Regulated by ERα in Breast Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2543 ◽  
Author(s):  
Shuning Wang ◽  
Xiaoju Li ◽  
Wangqian Zhang ◽  
Yuan Gao ◽  
Kuo Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor Alpha ◽  
Microarray Dataset ◽  
Rna Seq ◽  
Bioinformatics Analyses ◽  
Genome Wide ◽  
Breast Cancer Growth ◽  
The Relationship ◽  
Proliferation And Invasion ◽  
Mcf 7

Estrogen receptor alpha (ERα), which has been detected in over 70% of breast cancer cases, is a driving factor for breast cancer growth. For investigating the underlying genes and networks regulated by ERα in breast cancer, RNA-seq was performed between ERα transgenic MDA-MB-231 cells and wild type MDA-MB-231 cells. A total of 267 differentially expressed genes (DEGs) were identified. Then bioinformatics analyses were performed to illustrate the mechanism of ERα. Besides, by comparison of RNA-seq data obtained from MDA-MB-231 cells and microarray dataset obtained from estrogen (E2) stimulated MCF-7 cells, an overlap of 126 DEGs was screened. The expression level of ERα was negatively associated with metastasis and EMT in breast cancer. We further verified that ERα might inhibit metastasis by regulating of VCL and TNFRSF12A, and suppress EMT by the regulating of JUNB and ID3. And the relationship between ERα and these genes were validated by RT-PCR and correlation analysis based on TCGA database. By PPI network analysis, we identified TOP5 hub genes, FOS, SP1, CDKN1A, CALCR and JUNB, which were involved in cell proliferation and invasion. Taken together, the whole-genome insights carried in this work can help fully understanding biological roles of ERα in breast cancer.

scholarly journals Identification and Analysis of Estrogen Receptor α Promoting Tamoxifen Resistance-Related lncRNAs

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiulei Zhang ◽  
Shanjun Gao ◽  
Zhen Li ◽  
Wei Wang ◽  
Guangzhi Liu
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Estrogen Receptor Alpha ◽  
Acquired Resistance ◽  
Tamoxifen Resistance ◽  
Estrogen Receptor Α ◽  
Rna Seq ◽  
Breast Cancer Patients ◽  
Mcf 7

70-75% breast cancer patients are estrogen receptor alpha positive (ERα+), and the antiestrogen drug tamoxifen has been used for the past three decades. However, in 20-30% of these patients, tamoxifen therapy fails due to intrinsic or acquired resistance. A previous study has showed ERα signaling still exerts significant roles in the development of tamoxifen resistance and several lncRNAs have been demonstrated important roles in tamoxifen resistance. But ERα directly regulated and tamoxifen resistance related lncRNAs remain to be discovered. We reanalyze the published ERα chromatin immunoprecipitation-seq (ChIP-seq) and RNA-seq data of tamoxifen-sensitive (MCF-7/WT) and tamoxifen-resistant (MCF-7/TamR) breast cancer cells. We demonstrate that there are differential ERα recruitment events and the differentials may alert the expression profile in MCF-7/WT and MCF-7/TamR cells. Furthermore, we make an overlap of the ERα binding lncRNAs and differentially expressed lncRNAs and get 49 ERα positively regulated lncRNAs. Among these lncRNAs, the expression levels of AC117383.1, AC144450.1, RP11-15H20.6, and ATXN1-AS1 are negatively correlated with the survival probability of breast cancer patients and ELOVL2-AS1, PCOLCE-AS1, ITGA9-AS1, and FLNB-AS1 are positively correlated. These lncRNAs may be potential diagnosis or prognosis markers of tamoxifen resistance.

scholarly journals CD73-Mediated Immunosuppression Is Linked to a Specific Fibroblast Population That Paves the Way for New Therapy in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5878
Author(s):  
Ilaria Magagna ◽  
Nicolas Gourdin ◽  
Yann Kieffer ◽  
Monika Licaj ◽  
Rana Mhaidly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
Breast Cancer Patients ◽  
Large Collection ◽  
Functional Assays ◽  
Regulatory T Lymphocytes ◽  
Potential Clinical Benefit ◽  
Cd73 Expression

Background: Cancer-associated fibroblasts (CAF) are heterogeneous with multiple functions in breast cancer. Recently, we identified a specific CAF subpopulation (referred to as CAF-S1), which promotes immunosuppression and immunotherapy resistance. Methods and Results: Here, by studying a large collection of human samples, we highlight the key function of CD73/NT5E in CAF-S1-mediated immunosuppression in breast cancer. We first reveal that CD73 protein level specifically accumulates in CAF-S1 in breast cancer patients. Interestingly, infiltration of regulatory T lymphocytes (Tregs) is significantly correlated with CD73 expression in stroma but not in epithelium, indicating that CD73 contributes to immunosuppression when expressed in CAF-S1 and not in tumor cells. By performing functional assays based on relevant systems using primary CAF-S1 isolated from patients, we demonstrate that CAF-S1 increase the content in both PD-1+ and CTLA-4+ Tregs. Importantly, the use of a blocking anti-CD73 antibody on CAF-S1 reduces CAF-S1-mediated immunosuppression by preventing expression of these immune checkpoints on Tregs. Conclusions: Our data support the potential clinical benefit of using both anti-CD73 and immune-checkpoint inhibitors in breast cancer patients for inhibiting CAF-S1-mediated immunosuppression and enhancing anti-tumor immune response.

MELK is a downstream target of Del-1 and promotes breast cancer progression.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12578-e12578
Author(s):  
Soo Jung Lee ◽  
Yee Soo Chae ◽  
Jeeyeon Lee ◽  
Jieun Kang ◽  
Eun Ae Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Cancer Cell Line ◽  
Rna Seq ◽  
Breast Cancer Patients ◽  
Mcf 7

e12578 Background: Del-1 is a promising prognostic marker for breast cancer in our previous study. However, the downstream targets and biological effectors of Del-1 remain unclear and still untargetable in breast cancer. We performed transcriptome analysis using RNA-seq and explored the mechanism of Del-1 in regulating the progression of breast cancer to find druggable target. Methods: Total RNA was isolated using RNAiso Plus (TaKaRa, Otsu, Shiga, Japan), Libraries were prepared from total RNA using the NEBNext Ultra II Directional RNA-Seq Kit. High-throughput sequencing was performed as paired-end 100 sequencing using NovaSeq 6000 (Illumina, Inc., USA). OTSSP167(OTS167) were treated for inhibition of MELK. The effects of MELK on cell proliferation, invasion were determined using MTT, Matrigel Transwell assays. The tumoral expression of Del-1 and MELK were determined based on tissue microarrays and immunohistochemistry results from 440 early breast cancer patients. Results: To investigate Del-1 downregulation effect on breast cancer, we performed RNA-seq of Del-1 knock downed MDA-MB-231 and MCF 7-Tamoxifen resistant (TamR) cell line. Compared with si-control, MELK gene were downregulated in both knock downed cell lines. While a high Del-1 and MELK mRNA expressions were found in all the breast cancer cell lines, both expressions were significantly higher in MDA MB-231. MELK inhibitor (OTS167) treatment to breast cancer cell line MDA-MB-231 and MCF 7-TamR showed similar results as Del-1 down regulation by si-RNA. Inhibition of MELK suppressed proliferation and invasion of breast cancer cell line. Tumoral MELK expression correlate with increased aggressiveness and poor clinical outcomes in 440 breast cancer patients. Conclusions: Our results indicate that Del-1 may regulate MELK expression which has a role in breast cancer progression. In conclusion, modulation of Del-1 status by targeting MELK may be a new therapeutic strategy for breast cancer patients.

scholarly journals Evolutionary exploitation of PD-L1 expression in hormone receptor positive breast cancer

2018 ◽  
Author(s):  
Jeffrey West ◽  
Derek Park ◽  
Cathal Harmon ◽  
Drew Williamson ◽  
Peter Ashcroft ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Checkpoint Inhibitors ◽  
Prognostic Score ◽  
Expression Patterns ◽  
Metastatic Potential ◽  
Tumor Burden ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

AbstractBased on clinical data from hormone positive breast cancer patients, we determined that there is a potential tradeoff between reducing tumor burden and altering metastatic potential when administering combination therapy of aromatase inhibitors and immune checkpoint inhibitors. While hormone-deprivation therapies serve to reduce tumor size in the neoadjuvant setting pre-surgery, they may induce tumors to change expression patterns towards a metastatic phenotype. We used mathematical modeling to explore how the timing of the therapies affects tumor burden and metastatic potential with an eye toward developing a dynamic prognostic score and reducing both tumor size and risk of metastasis.

scholarly journals Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3530
Author(s):  
Penn Muluhngwi ◽  
Carolyn M. Klinge
Keyword(s):  
Breast Cancer ◽  
Cancer Survival ◽  
Expression Patterns ◽  
Endocrine Resistance ◽  
Estrogen Receptor Α ◽  
Resistant Cell ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Non Coding Rnas ◽  
Mcf 7

Despite improvements in the treatment of endocrine-resistant metastatic disease using combination therapies in patients with estrogen receptor α (ERα) primary tumors, the mechanisms underlying endocrine resistance remain to be elucidated. Non-coding RNAs (ncRNAs), including microRNAs (miRNA) and long non-coding RNAs (lncRNA), are targets and regulators of cell signaling pathways and their exosomal transport may contribute to metastasis. Previous studies have shown that a low expression of miR-29a-3p and miR-29b-3p is associated with lower overall breast cancer survival before 150 mos. Transient, modest overexpression of miR-29b1-3p or miR-29a-3p inhibited MCF-7 tamoxifen-sensitive and LCC9 tamoxifen-resistant cell proliferation. Here, we identify miR-29b-1/a-regulated and non-regulated differentially expressed lncRNAs in MCF-7 and LCC9 cells using next-generation RNA seq. More lncRNAs were miR-29b-1/a-regulated in LCC9 cells than in MCF-7 cells, including DANCR, GAS5, DSCAM-AS1, SNHG5, and CRND. We examined the roles of miR-29-regulated and differentially expressed lncRNAs in endocrine-resistant breast cancer, including putative and proven targets and expression patterns in survival analysis using the KM Plotter and TCGA databases. This study provides new insights into lncRNAs in endocrine-resistant breast cancer.

scholarly journals The molecular landscape of Asian breast cancers reveals clinically relevant population-specific differences

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jia-Wern Pan ◽  
Muhammad Mamduh Ahmad Zabidi ◽  
Pei-Sze Ng ◽  
Mei-Yee Meng ◽  
Siti Norhidayu Hasan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Somatic Mutations ◽  
Checkpoint Inhibitors ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Breast Tumours ◽  
Different Populations ◽  
Caucasian Women ◽  
Molecular Landscape ◽  
Immune Score

AbstractMolecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.

scholarly journals Abnormal Long Non-Coding RNAs Expression Patterns Have the Potential Ability for Predicting Survival and Treatment Response in Breast Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 996
Author(s):  
Ana Carolina Pavanelli ◽  
Flavia Rotea Mangone ◽  
Luciana R. C. Barros ◽  
Juliana Machado-Rugolo ◽  
Vera L. Capelozzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Predictive Value ◽  
Expression Patterns ◽  
Survival Rates ◽  
In Silico Analysis ◽  
Cancer Prognosis ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Non Coding Rnas

Abnormal long non-coding RNAs (lncRNAs) expression has been documented to have oncogene or tumor suppressor functions in the development and progression of cancer, emerging as promising independent biomarkers for molecular cancer stratification and patients’ prognosis. Examining the relationship between lncRNAs and the survival rates in malignancies creates new scenarios for precision medicine and targeted therapy. Breast cancer (BRCA) is a heterogeneous malignancy. Despite advances in its molecular classification, there are still gaps to explain in its multifaceted presentations and a substantial lack of biomarkers that can better predict patients’ prognosis in response to different therapeutic strategies. Here, we performed a re-analysis of gene expression data generated using cDNA microarrays in a previous study of our group, aiming to identify differentially expressed lncRNAs (DELncRNAs) with a potential predictive value for response to treatment with taxanes in breast cancer patients. Results revealed 157 DELncRNAs (90 up- and 67 down-regulated). We validated these new biomarkers as having prognostic and predictive value for breast cancer using in silico analysis in public databases. Data from TCGA showed that compared to normal tissue, MIAT was up-regulated, while KCNQ1OT1, LOC100270804, and FLJ10038 were down-regulated in breast tumor tissues. KCNQ1OT1, LOC100270804, and FLJ10038 median levels were found to be significantly higher in the luminal subtype. The ROC plotter platform results showed that reduced expression of these three DElncRNAs was associated with breast cancer patients who did not respond to taxane treatment. Kaplan–Meier survival analysis revealed that a lower expression of the selected lncRNAs was significantly associated with worse relapse-free survival (RFS) in breast cancer patients. Further validation of the expression of these DELncRNAs might be helpful to better tailor breast cancer prognosis and treatment.

Sign in / Sign up

Export Citation Format

Share Document