scholarly journals Bioinformatic Analysis of Peripheral Blood miRNA of Breast Cancer Patients in Relation With Anthracycline Cardiotoxicity

2019 ◽  
Author(s):  
Wang Yadi ◽  
Chen Shurui ◽  
Zhang Tong ◽  
Chen Suxian ◽  
Tong Qing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Cancer Chemotherapy ◽  
Bioinformatic Analysis ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Anthracycline Cardiotoxicity ◽  
Breast Cancer Chemotherapy

Abstract The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of anthracycline cardiotoxicity.

scholarly journals Bioinformatic Analysis of Peripheral Blood miRNA of Breast Cancer Patients in Relation With Anthracycline Cardiotoxicity

2019 ◽  
Author(s):  
Wang Yadi ◽  
Chen Shurui ◽  
Zhang Tong ◽  
Chen Suxian ◽  
Tong Qing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Cancer Chemotherapy ◽  
Bioinformatic Analysis ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Anthracycline Cardiotoxicity ◽  
Breast Cancer Chemotherapy

Abstract The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of anthracycline cardiotoxicity.

scholarly journals Bioinformatic Analysis of Peripheral Blood miRNA of Breast Cancer Patients in Relation With Anthracycline Cardiotoxicity

2019 ◽  
Author(s):  
Wang Yadi ◽  
Chen Shurui ◽  
Zhang Tong ◽  
Chen Suxian ◽  
Tong Qing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Cancer Chemotherapy ◽  
Bioinformatic Analysis ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Anthracycline Cardiotoxicity ◽  
Breast Cancer Chemotherapy

Abstract The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of anthracycline cardiotoxicity.

scholarly journals Bioinformatic Analysis of Peripheral Blood miRNA of Breast Cancer Patients in Relation With Anthracycline Cardiotoxicity

2019 ◽  
Author(s):  
Wang Yadi ◽  
Chen Shurui ◽  
Zhang Tong ◽  
Chen Suxian ◽  
Tong Qing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Cancer Chemotherapy ◽  
Bioinformatic Analysis ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Anthracycline Cardiotoxicity ◽  
Breast Cancer Chemotherapy

Abstract The current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of anthracycline cardiotoxicity.

scholarly journals How are health literacy principles incorporated into breast cancer chemotherapy education? A review of the literature

2018 ◽  
Vol 8 (6) ◽  
pp. 77 ◽  
Author(s):  
Pearman D. Parker ◽  
Sue P. Heiney ◽  
Daniela B. Friedman ◽  
Tisha M. Felder ◽  
Robin Dawson Estrada ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Health Literacy ◽  
Cancer Patients ◽  
Cancer Chemotherapy ◽  
Cochrane Library ◽  
Breast Cancer Patients ◽  
Plain Language ◽  
Breast Cancer Chemotherapy ◽  
Mesh Terms ◽  
Written Materials

Background: Chemotherapy is commonly used in combination with other treatments for breast cancer. However, low adherence to chemotherapy is a growing concern, particularly among breast cancer patients. Side effects such as nausea and vomiting, fatigue, and arthralgia can contribute to reduced adherence. Other factors such as provider communication and limited insurance coverage can affect adherence. Studies have shown that as much as 28% of patients with breast cancer did not continue with their prescribed dose of chemotherapy. Research suggests that chemotherapy education materials can be critical to addressing problems with non-adherence, and may include written materials, verbal instruction, and multimedia programs. Despite this wide variety, the effectiveness and benefit of chemotherapy education hinges on the patients’ health literacy.  Breast cancer patients with low health literacy may be unclear about chemotherapy or face difficulty adhering to treatment if they do not understand the information provided to them. Thus, this scoping review summarizes the existing research on how health literacy principles are incorporated into breast cancer chemotherapy education materials.Methods: Using a combination of keywords (e.g. chemotherapy, education) and Medical subject headings (MeSH) terms (e.g., drug therapy, antineoplastic agents), we searched five databases (1977-2017): CINAHL, PubMed, PsycINFO, Cochrane Library, and Web of Science.Results: Eight of 4,624 articles met the inclusion criteria. Five articles incorporated health literacy principles (e.g., plain language, maintaining an active voice, using white space) into the development of written materials. Few articles used a theoretical framework to guide education material development (n = 3). Of the three articles that described pilot-testing of educational materials, two used post-tests only and one used a pre/post-test design.Conclusions: Findings indicated that limited research exists regarding the use of health literacy principles in chemotherapy education materials. Much of the development of chemotherapy education is not grounded in theory and the application of health literacy principles is limited. Implementing health literacy principles may improve overall comprehension of education thereby increasing adherence.

scholarly journals PENGARUH KONSELING TERHADAP TINGKAT PEMAHAMAN PENYAKIT DAN EFEK SAMPING OBAT KEMOTERAPI PADA PASIEN KANKER PAYUDARA DI UNIT KEMOTERAPI SALAH SATU RUMAH SAKIT DI KOTA MALANG

2021 ◽  
Vol 1 (2) ◽  
pp. 36-41
Author(s):  
Angga Dian Prastowo
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Cancer Chemotherapy ◽  
Wilcoxon Test ◽  
P Value ◽  
Breast Cancer Patients ◽  
Breast Cancer Chemotherapy ◽  
Before And After ◽  
Level Of Understanding

AbstrakKanker payudara adalah penyebab kematian terbesar pada wanita. Salah satu hal yang penting untuk diperhatikan adalah pada pasien kanker payudara yang menjalani kemoterapi akan mengalami efek samping mual muntah, rambut rontok, nyeri, kehilangan nafsu makan dan lain- lain. Penelitian saat ini bertujuan untuk mengetahui pengaruh konseling terhadap tingkat pemahaman penyakit dan efek samping kemoterapi pasien kanker payudara Penderita kanker payudara perlu mengetahui penyakitnya dengan baik agar kualitas hidupnya dapat tetap terjaga. Edukasi yang dilakukan secara perseorangan maupun kelompok pada penderita tentang efek samping obat kemoterapi sangat diperlukan supaya penderita tidak merasa cemas apabila mengalami efek dari kemoterapi tersebut. Pemberian konseling oleh Apoteker pada pasien kemoterapi kanker payudara sangat penting karena dapat meningkatkan pengetahuan pasien, kepatuhan pasien dalam pengobatannya serta dapat meningkatkan kualitas hidup pasien. Tujuan penelitian ini untuk mengetahui pengaruh pemberian konseling oleh Apoteker terhadap tingkat pemahaman penyakit dan efek samping kemoterapi pada pasien kanker payudara di Unit Kemoterapi Salah Satu Rumkit Pemerintah Di Kota Malang..Penelitian ini merupakan studi kuantitatif dengan desain Pre-Experimental berupa pretest-postes design. Banyaknya sampel yang diambil didasarkan atas waktu yaitu selama satu bulan dan sampel diambil dengan metode consecutive sampling. Hasil penelitian menggunakan uji Wilcoxon menunjukkan terdapat perbedaan nilai sebelum dan sesudah diberikan konseling oleh apoteker terhadap pasien kemoterapi kanker payudara dengan nilai signifikansi sebesar 0,000 (P value< 0,05). Kesimpulan pada penelitian ini adalah pemberian konseling oleh apoteker dapat meningkatkan tingkat pemahaman penyakit dan efek samping dari kemoterapi kanker payudara.Kata kunci : konseling, pemahaman, penyakit kanker payudara, efek samping kemoterapi Abstract Breast cancer is the leading cause of death in women. One important thing to note is that breast cancer patients who undergo chemotherapy experience side effects of nausea and vomiting, hair loss, pain, loss of appetite and others. The current study aims to determine the effect of counseling on the level of understanding of the disease and the side effects of breast cancer chemotherapy patients Breast cancer patients need to know the disease well to the quality of life can be maintained. Education is done individually or in groups to the patient about the side effects of chemotherapy drugs is indispensable so that the patient does not feel anxious when experiencing the effects of chemotherapy. Provision of counseling by pharmacists in patients with breast cancer chemotherapy is very important because it can improve patient knowledge, patient compliance in the treatment and can improve the quality of life of patients. The purpose of this study to determine the effect of counseling by pharmacists to the level of understanding of the disease and the side effects of chemotherapy in breast cancer patients on Chemotherapy Unit One Government Hospital In Malang .. This research is a quantitative study with Pre-Experimental design in the form of a pretestposttest design. The number of samples taken based on the time that is for one month and samples were taken with consecutive sampling method. The results using the Wilcoxon test shows that there are differences in values before and after counseling by pharmacists to patients with breast cancer chemotherapy with a significance value of 0.000 (p value <0.05). Conclusion of this research is the provision of counseling by pharmacists can improve the level of understanding of the disease and the side effects of breast cancerchemotherapy. The results using the Wilcoxon test shows that there are differences in values before and after counseling by pharmacists to patients with breast cancer chemotherapy with a significance value of 0.000 (p value <0.05). Conclusion of this research is the provision of counseling by pharmacists can improve the level of understanding of the disease and the side effects of breast cancer chemotherapy. The results using the Wilcoxon test shows that there are differences in values before and after counseling by pharmacists to patients with breast cancer chemotherapy with a significance value of 0.000 (p value <0.05). Conclusion of this research is the provision of counseling by pharmacists can improve the level of understanding of the disease and the side effects of breast cancer chemotherapy. Keywords : Counseling, understanding, breast cancer, chemotherapy side effects

scholarly journals Differential impact of classical and non-canonical NF-κB pathway-related gene expression on the survival of breast cancer patients

2019 ◽  
Vol 10 (21) ◽  
pp. 5191-5211 ◽  
Author(s):  
Nancy Adriana Espinoza-Sánchez ◽  
Balázs Győrffy ◽  
Ezequiel M. Fuentes-Pananá ◽  
Martin Götte
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Differential Impact

scholarly journals Carrying G allele in rs786204926 involved in alternative splicing of PTEN is associated with chemosensitivity in breast cancer

2021 ◽  
Author(s):  
Jing Wang ◽  
Shasha Zhang ◽  
Jiaxin Zhang ◽  
Zhongliang Zhang ◽  
Qinglong Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Alternative Splicing ◽  
Gene Polymorphism ◽  
Cancer Patients ◽  
Cancer Chemotherapy ◽  
Receptor Site ◽  
Pten Gene ◽  
Breast Cancer Patients ◽  
Breast Cancer Chemotherapy ◽  
Cancer Chemoresistance

Abstract Background Chemoresistance is still the main reason for the failure of breast cancer treatment and is the main cause of death of breast cancer patients. Although many studies have shown the association between genetic polymorphisms of PTEN and chemoresistance, the molecular mechanism of breast cancer chemotherapy has not been further studied. This study aims to investigate the potential association between novel PTEN gene polymorphism and breast chemoresistance in Chinese population, and explore whether alternative splicing of the PTEN gene is affected by the gene polymorphism. Methods The study included 234 patients with breast cancer chemotherapy, 157 chemosensitive cases and 77 chemoresistant case. rs786204926, rs701848, rs12402181, rs35770269 were analysed using Sanger sequence and Sequenom MassArray typing technology. Silicon analysis was used to predict whether and how the polymorphism affects alternative splicing. Semi-quantitative RT-PCR and Western blot were further used to validate the silicon analysis. Results It is showed that there was a significant association between rs786204926 polymorphism and breast cancer chemoresistance. Carrying G allele or AG genotype will increase the risk of chemosensitivity in breast cancer. Additionally, Logistic multivariate regression analysis showed that age, lymph node metastasis and rs786204926 genotype are risk factors for breast cancer chemoresistance. Furthermore, Silico analysis showed that carrying G allele or AG genotype in chemosensitivity samples produced a new receptor site of alternative splicing, which increases the possibility of a new mutant PTEN isoform production. Interestingly, further experiments also verify this possibility. Conclusion We speculate that the mechanism of breast cancer chemosensitivity might be caused by a change in alternative splicing caused by the rs786204926 of PTEN gene. Thus, our study might provide theoretical guidance for the individualized treatment of clinical breast cancer patients.

scholarly journals A glycolysis-related gene expression signature in predicting recurrence of breast cancer

2020 ◽  
Author(s):  
Jianing Tang ◽  
Gaosong Wu
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Group ◽  
Gene Signature ◽  
Low Risk ◽  
Individual Treatment ◽  
Breast Cancer Patients ◽  
Related Gene

Abstract Background Metabolic change is the hallmark of cancer. Even in the presence of oxygen, cancer cells reprogram their glucose metabolism to enhance glycolysis and reduce oxidative phosphorylation. In the present study, we aimed to develop a glycolysis-related gene signature to predict the prognosis of breast cancer patients.Methods Gene expression profiles and clinical data of breast cancer patients were obtained from the GEO database. Univariate, Lasso-penalized, and multivariate Cox analysis were performed to construct the glycolysis-related gene signature.Results A four-gene based signature (ALDH2, PRKACB, STMN1 and ZNF292) was developed to separate patients into high-risk and low-risk groups. Kaplan-Meier survival analysis demonstrated that patients in low-risk group had significantly better prognosis than those in the high-risk group. Time-dependent ROC analysis demonstrated that the glycolysis-related gene signature had excellent prognostic accuracy. We further confirmed the expression of the four prognostic genes in breast cancer and paracancerous tissues samples using qRT-PCR analysis. Expression level of PRKACB was higher in paracancerous tissues, while STMN1 and ZNF292 were overexpressed in tumor samples. No difference was found in ALDH2 expression. The same results were observed in the IHC data from the human protein atlas. Global proteome data of 105 TCGA breast cancer samples obtained from the Clinical Proteomic Tumor Analysis Consortium were used to evaluate the prognostic value of their protein levels. Consistently, high expression of PRKACB protein level was associated with better prognosis, while high ZNF292 and STMN1 protein expression levels indicated poor prognosis.Conclusions The glycolysis-related gene signature might provide an effective prognostic predictor and a new view for individual treatment of breast cancer patients.

c-kit: Identification of co-regulated genes by gene expression profiling and clinical relevance of two breast cancer subtypes with stem cell like features

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 622-622 ◽  
Author(s):  
A. Rody ◽  
U. Holtrich ◽  
V. Müller ◽  
R. Gaetje ◽  
R. Diallo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Stem Cell ◽  
Gene Expression Profiling ◽  
Cancer Patients ◽  
Expression Profiling ◽  
Breast Cancer Subtypes ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Cancer Subtypes

622 Background: Expression of the proto-oncogene c-kit has been found in malignant tissue including a subset of breast cancers. c-Kit is also expressed in normal breast tissue and several authors found a loss of c-kit expression in breast carcinoma suggesting it might be involved in the growth control of mammary epithelium. Until now, only a few markers were described to be co-regulated with c-kit. To elucidate the possible role of c-kit in malignant transformation, we analyzed gene expression data of breast cancer patients. Methods: Tumor tissue of n=171 breast cancer patients were analyzed by gene expression profiling using Affymetrix Hg U133 Arrays (22,500 genes) and bioinformatic analyses. Tumor samples with high stromal and low epithelial cell content by gene expression profiling were excluded for further analysis. Validation was performed with n=100 independent samples. Results: A total of 10.5% of the tumors showed strong c-kit expression (2.5 fold above median). A careful dissection of global expression data revealed strong correlations of c-kit with the expression of a large cluster of genes containing several for whom c-kit coexpression was already described (HER1, CK-5/-17, PDGFR) as well as several members of the wnt signalling pathway, providing a possible novel link to mammary epithelial differentiation. Analysis of n=171 breast cancer samples according to this gene set allows the identification of putative “stem cell like” tumors (SCL) characterized by expression of several known stem cell markers. Surprisingly, a tight link of ER status and proliferation is restricted only to these SCL tumors but lost among non-SCL tumors. The clinical implications of our findings will be presented. Conclusions: For the first time these data bring together the description of two breast cancer subtypes identified by gene expression profiling with the actual stem cell model of the development of breast cancer. No significant financial relationships to disclose.

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