scholarly journals Immune gene expression profiling reveals heterogeneity in luminal breast tumors

2019 ◽  
Author(s):  
Bin Zhu ◽  
Shelly Lap Ah Tse ◽  
Difei Wang ◽  
Hela Koka ◽  
Tongwu Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Gene Expression Profiling ◽  
T Cell Activation ◽  
Expression Profiling ◽  
Expression Patterns ◽  
Luminal Breast Cancer ◽  
Immune Gene ◽  
Disease Heterogeneity ◽  
Immune Gene Expression

AbstractDisease heterogeneity of immune gene expression patterns of luminal breast cancer (BC) has not been well studied. We performed immune gene expression profiling of tumor and adjacent normal tissue in 92 Asian luminal BC patients and identified three distinct immune subtypes. Tumors in one subtype exhibited signs of T-cell activation, lower ESR1/ESR2 expression ratio and higher expression of immune checkpoint genes, nonsynonymous mutation burden, APOBEC-signature mutations, and increasing body mass index compared to other luminal tumors. Tumors in a second subtype were characterized by increased expression of interferon-stimulated genes and enrichment for TP53 somatic mutations. The presence of three immune subtypes within luminal BC was replicated in cases drawn from The Cancer Genome Atlas and a Korean breast cancer study. Our findings suggest that immune gene expression and associated genomic features could be useful to further stratify luminal BC beyond the current luminal A/B classification.

scholarly journals Immune gene expression profiling reveals heterogeneity in luminal breast tumors

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Bin Zhu ◽  
Lap Ah Tse ◽  
Difei Wang ◽  
Hela Koka ◽  
Tongwu Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Expression Profiling ◽  
Normal Tissue ◽  
Breast Tumors ◽  
Immune Gene ◽  
Deletion Polymorphism ◽  
Genomic Features ◽  
Immune Gene Expression ◽  
Asian Populations

Abstract Background Heterogeneity of immune gene expression patterns of luminal breast cancer (BC), which is clinically heterogeneous and overall considered as low immunogenic, has not been well studied especially in non-European populations. Here, we aimed at characterizing the immune gene expression profile of luminal BC in an Asian population and associating it with patient characteristics and tumor genomic features. Methods We performed immune gene expression profiling of tumor and adjacent normal tissue in 92 luminal BC patients from Hong Kong using RNA-sequencing data and used unsupervised consensus clustering to stratify tumors. We then used luminal patients from The Cancer Genome Atlas (TCGA, N = 564) and a Korean breast cancer study (KBC, N = 112) as replication datasets. Results Based on the expression of 130 immune-related genes, luminal tumors were stratified into three distinct immune subtypes. Tumors in one subtype showed higher level of tumor-infiltrating lymphocytes (TILs), characterized by T cell gene activation, higher expression of immune checkpoint genes, higher nonsynonymous mutation burden, and higher APOBEC-signature mutations, compared with other luminal tumors. The high-TIL subtype was also associated with lower ESR1/ESR2 expression ratio and increasing body mass index. The comparison of the immune profile in tumor and matched normal tissue suggested a tumor-derived activation of specific immune responses, which was only seen in high-TIL patients. Tumors in a second subtype were characterized by increased expression of interferon-stimulated genes and enrichment for TP53 somatic mutations. The presence of three immune subtypes within luminal BC was replicated in TCGA and KBC, although the pattern was more similar in Asian populations. The germline APOBEC3B deletion polymorphism, which is prevalent in East Asian populations and was previously linked to immune activation, was not associated with immune subtypes in our study. This result does not support the hypothesis that the germline APOBEC3B deletion polymorphism is the driving force for immune activation in breast tumors in Asian populations. Conclusion Our findings suggest that immune gene expression and associated genomic features could be useful to further stratify luminal BC beyond the current luminal A/B classification and a subset of luminal BC patients may benefit from checkpoint immunotherapy, at least in Asian populations.

Different patterns of non immediate allergic reaction to BRAF inhibitor in two patients with metastatic melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21052-e21052 ◽  
Author(s):  
Miguel-Angel Berciano-Guerrero ◽  
Rocío Lavado ◽  
Álvaro Montesa ◽  
Martina Alvarez ◽  
Angela Santonja ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Gene Expression Profiling ◽  
Metastatic Melanoma ◽  
Expression Profiling ◽  
Braf Inhibitor ◽  
Braf V600e ◽  
Immune Gene ◽  
Skin Reactions ◽  
Immune Gene Expression

e21052 Background: Non immediate allergic reactions (niAR) related with oncology drugs are a rare entity. Usually, it is called Drug Reaction with eosinophilia and sistemic symptoms (“DRESS”), occurring at first ten days of treatment.Recently, the treatment of metastatic melanoma (MM) has included new drugs in patients wtih BRAF V600E mutation. Despite skin reactions are usual, niAR to these drugs have not been reported. We present 2 clinical cases with mm treated with BRAFi, developing such niAR. Methods: Patient 1: 47yo female with lymph node relapse and multiple subcutaneous skin metastases (previously pT1N0M0 melanoma) that received nivolumab in adjuvant setting. BRAF-mutated. She starts with Vemurafenib-Cobimetinib (V-C). At 8 days, niAR (maculo-papular exantema G4, fever G2). After discontinuation of this treatment (3 weeks), it is changed to Dabrafenib(50%)-Trametinib (D-T). With only 1 dose, skin niAR (G3) is newly developed. Biopsy are taken at the beginning (T0), during (T1) and after desentizitation (T2). Patient 2: 60 yo female, lung and lymph node relapse of melanoma (previously pT2bN0M0) after IFN-alpha adjuvant 2 years before. BRAF-mutated. Start with V-C. At 9 days, skin niAR (G4), with fever (G1). Discontinuation of treatment. Biopsys and blood test are taken (T0, T1 and T2). Gene expression was performed with PanCancer Immune Profiling Panel Nanostring™ in this points. Results: Different lymphocytic subpopulations in blood and biopsy at acute phase are showed in table 1. Immune gene expression profiling found decreased expression of 5 genes: UBC, IL8, IL32, NFKB1A and FOS, increasing IFNGR1 (pt 1). In both of pts, desensitizitation protocol by Allergologists was made succesfully, with incremental oncology drugs and steroid reduction protocol. Both of pts had a maior partial response (RECIST), even the scarce of the drug received. Conclusions: D and V develop important “of class” skin niAR. Different immunologic patterns are related with this niAR. Previous exposition to IFN or anti-PD1 therapy might modulate such response. Immune gene expression profiling could be used as a method to identify biomarkers. Desensitization with BRAFi has enough efficacy and tolerance.

Prediction of Docetaxel Response in Human Breast Cancer by Gene Expression Profiling

2005 ◽  
Vol 23 (3) ◽  
pp. 422-431 ◽  
Author(s):  
Kyoko Iwao-Koizumi ◽  
Ryo Matoba ◽  
Noriko Ueno ◽  
Seung Jin Kim ◽  
Akiko Ando ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Side Effects ◽  
Gene Expression Profiling ◽  
Clinical Response ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Redox System ◽  
Response To Therapy

Purpose Docetaxel is one of the most effective anticancer drugs available in the treatment of breast cancer. Nearly half of the treated patients, however, do not respond to chemotherapy and suffer from side effects. The ability to reliably predict a patient's response based on tumor gene expression will improve therapeutic decision making and save patients from unnecessary side effects. Patients and Methods A total of 44 breast tumor tissues were sampled by biopsy before treatment with docetaxel, and the response to therapy was clinically evaluated by the degree of reduction in tumor size. Gene expression profiling of the biopsy samples was performed with 2,453 genes using a high-throughput reverse transcriptase polymerase chain reaction technique. Using genes differentially expressed between responders and nonresponders, a diagnostic system based on the weighted-voting algorithm was constructed. Results This system predicted the clinical response of 26 previously unanalyzed samples with over 80% accuracy, a level promising for clinical applications. Diagnostic profiles in nonresponders were characterized by elevated expression of genes controlling the cellular redox environment (ie, redox genes, such as thioredoxin, glutathione-S-transferase, and peroxiredoxin). Overexpression of these genes protected cultured mammary tumor cells from docetaxel-induced cell death, suggesting that enhancement of the redox system plays a major role in docetaxel resistance. Conclusion These results suggest that the clinical response to docetaxel can be predicted by gene expression patterns in biopsy samples. The results also suggest that one of the molecular mechanisms of the resistance is activation of a group of redox genes.

scholarly journals 581P VHIO immune gene expression profiling (VIGex) panel, a tool to explore tumour immune microenvironment

2020 ◽  
Vol 31 ◽  
pp. S492-S493
Author(s):  
F.M. Mancuso ◽  
Z. Ogbah ◽  
R. Fasani ◽  
D.G. Lo Giacco ◽  
L. Ramos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Immune Gene ◽  
Immune Microenvironment ◽  
Immune Gene Expression
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