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Ye Liu, Mei Yuan, Chao Wu, Tianhui Zhu, Wei Sun
Breast cancer is the most common invasive cancer in women worldwide, and can be subdivided into Luminal A, Luminal B, Her2, and Basal subtype (the PAM50 subtyping system). The lmo2 gene was traditionally recognized as a proto-oncogene in hematopoietic system but its functions in breast cancers remained largely unclear. Based on the Cancer Genome Atlas (TCGA) breast cancer dataset, herein we found that the significantly LMO2-correlated genes in normal or malignant samples were enriched in rather divergent cellular pathways, suggesting the function complexity of LMO2 in breast tissues...
February 6, 2018: Oncotarget
Inyoung Kim, Saemi Choi, Sun Kim
BACKGROUND: Bioinformatics research for finding biological mechanisms can be done by analysis of transcriptome data with pathway based interpretation. Therefore, researchers have tried to develop tools to analyze transcriptome data with pathway based interpretation. Over the years, the amount of omics data has become huge, e.g., TCGA, and the data types to be analyzed have come in many varieties, including mutations, copy number variations, and transcriptome. We also need to consider a complex relationship with regulators of genes, particularly Transcription Factors(TF)...
February 19, 2018: BMC Bioinformatics
Tania B Porras, Pushpinder Kaur, Alexander Ring, Naomi Schechter, Julie E Lang
Circulating tumor cells (CTCs) have potential utility as a surrogate biomarker of tumor biology via a liquid biopsy. The aim of this study was to evaluate if the nCounter NanoString assay could be used for accurate gene expression profiling of CTCs using the PAM50 research-use-only CodeSet. Analysis was performed on CTCs isolated by the ANGLE Parsortix system from healthy blood spiked with the breast cancer cell lines Hs578T, SkBr3, MDA-MB-231 or MCF7. Using cell lines as gold standard positive controls and Parsortix processed blood without spiking (unspiked) as negative controls, we found an average of 12 significantly differentially expressed genes among spiked samples versus unspiked controls...
January 23, 2018: Oncotarget
Ivana Sestak, Richard Buus, Jack Cuzick, Peter Dubsky, Ralf Kronenwett, Carsten Denkert, Sean Ferree, Dennis Sgroi, Catherine Schnabel, Frederick L Baehner, Elizabeth Mallon, Mitch Dowsett
Importance: Multiple molecular signatures are available for managing estrogen receptor (ER)-positive breast cancer but with little direct comparative information to guide the patient's choice. Objective: To conduct a within-patient comparison of the prognostic value of 6 multigene signatures in women with early ER-positive breast cancer who received endocrine therapy for 5 years. Design, Setting, and Participants: This retrospective biomarker analysis included 774 postmenopausal women with ER-positive ERBB2 (formerly HER2)-negative breast cancer...
February 15, 2018: JAMA Oncology
Una Kjällquist, Rikard Erlandsson, Nicholas P Tobin, Amjad Alkodsi, Ikram Ullah, Gustav Stålhammar, Eva Karlsson, Thomas Hatschek, Johan Hartman, Sten Linnarsson, Jonas Bergh
BACKGROUND: Tumor heterogeneity in breast cancer tumors is today widely recognized. Most of the available knowledge in genetic variation however, relates to the primary tumor while metastatic lesions are much less studied. Many studies have revealed marked alterations of standard prognostic and predictive factors during tumor progression. Characterization of paired primary- and metastatic tissues should therefore be fundamental in order to understand mechanisms of tumor progression, clonal relationship to tumor evolution as well as the therapeutic aspects of systemic disease...
February 12, 2018: BMC Cancer
Emma H Allott, Joseph Geradts, Stephanie M Cohen, Thaer Khoury, Gary R Zirpoli, Wiam Bshara, Warren Davis, Angela Omilian, Priya Nair, Rochelle P Ondracek, Ting-Yuan David Cheng, C Ryan Miller, Helena Hwang, Leigh B Thorne, Siobhan O'Connor, Traci N Bethea, Mary E Bell, Zhiyuan Hu, Yan Li, Erin L Kirk, Xuezheng Sun, Edward A Ruiz-Narvaez, Charles M Perou, Julie R Palmer, Andrew F Olshan, Christine B Ambrosone, Melissa A Troester
BACKGROUND: Breast cancer subtype can be classified using standard clinical markers (estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)), supplemented with additional markers. However, automated biomarker scoring and classification schemes have not been standardized. The aim of this study was to optimize tumor classification using automated methods in order to describe subtype frequency in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium...
February 6, 2018: Breast Cancer Research: BCR
Nelson Rangel, Milena Rondon-Lagos, Laura Annaratone, Simona Osella-Abate, Jasna Metovic, Maria Piera Mano, Luca Bertero, Paola Cassoni, Anna Sapino, Isabella Castellano
The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours. The aim of the present study was to analyse the prognostic impact of AR/ER ratio, evaluated by immunohistochemistry (IHC), correlating this value with clinical, pathological and molecular characteristics. We retrospectively selected a cohort of 402 ER+BC patients. On each tumour, IHC analyses for AR, ER, PgR, HER2 and Ki67 were performed and AR+ cases were used to calculate the AR/ER value...
March 2018: Endocrine-related Cancer
Anne-Vibeke Lænkholm, Maj-Britt Jensen, Jens Ole Eriksen, Birgitte Bruun Rasmussen, Ann S Knoop, Wesley Buckingham, Sean Ferree, Carl Schaper, Torsten O Nielsen, Taryn Haffner, Torben Kibøl, Maj-Lis Møller Talman, Anne Marie Bak Jylling, Tomasz Piotr Tabor, Bent Ejlertsen
Purpose The PAM50-based Prosigna risk of recurrence (ROR) score has been validated in randomized clinical trials to predict 10-year distant recurrence (DR). The value of Prosigna for predicting DR was examined in a comprehensive nationwide Danish cohort consisting of postmenopausal women with hormone receptor-positive early breast cancer treated with 5 years of endocrine therapy alone. Patients and Methods Using the population-based Danish Breast Cancer Cooperative Group database, follow-up data were collected on all patients diagnosed from 2000 through 2003 who, by nationwide guidelines, were treated with endocrine therapy for 5 years...
January 25, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Humberto Parada, Xuezheng Sun, Jodie M Fleming, ClarLynda R Williams-DeVane, Erin L Kirk, Linnea T Olsson, Charles M Perou, Andrew F Olshan, Melissa A Troester
BACKGROUND: We examined racial differences in the expression of eight genes and their associations with risk of recurrence among 478 white and 495 black women who participated in the Carolina Breast Cancer Study Phase 3. METHODS: Breast tumor samples were analyzed for PAM50 subtype and for eight genes previously found to be differentially expressed by race and associated with breast cancer survival: ACOX2, MUC1, FAM177A1, GSTT2, PSPH, PSPHL, SQLE, and TYMS. The expression of these genes according to race was assessed using linear regression and each gene was evaluated in association with recurrence using Cox regression...
December 11, 2017: Breast Cancer Research: BCR
Gustav Stålhammar, Stephanie Robertson, Lena Wedlund, Michael Lippert, Mattias Rantalainen, Jonas Bergh, Johan Hartman
AIMS: During pathological examination of breast tumours, proliferative activity is routinely evaluated by a count of mitoses. Adding immunohistochemical stains of Ki67 provides extra prognostic and predictive information. However, the currently used methods for these evaluations suffer from imperfect reproducibility. It is still unclear whether analysis of Ki67 should be performed in hot spots, in the tumour periphery, or as an average of the whole tumour section. The aim of this study was to compare the clinical relevance of mitoses, Ki67 and phosphohistone H3 in two cohorts of primary breast cancer specimens (total n = 294)...
December 8, 2017: Histopathology
Arunima Srivastava, Chaitanya Kulkarni, Parag Mallick, Kun Huang, Raghu Machiraju
Utilization of single modality data to build predictive models in cancer results in a rather narrow view of most patient profiles. Some clinical facet s relate strongly to histology image features, e.g. tumor stages, whereas others are associated with genomic and proteomic variations (e.g. cancer subtypes and disease aggression biomarkers). We hypothesize that there are coherent "trans-omics" features that characterize varied clinical cohorts across multiple sources of data leading to more descriptive and robust disease characterization...
2018: Pacific Symposium on Biocomputing
Anne-Vibeke Laenkholm, Maj-Britt Jensen, Jens Ole Eriksen, Wesley Buckingham, Sean Ferree, Torsten O Nielsen, Bent Ejlertsen
INTRODUCTION: The Prosigna-PAM50 risk of recurrence (ROR) score has been validated in randomized clinical trials to predict 10-year distant recurrence (DR) in hormone receptor-positive breast cancer. Here, we examine the ability of Prosigna for predicting DR at 10 years in a subgroup of postmenopausal breast cancer patients with special histological subtypes. METHODS: Using the population based Danish Breast Cancer Group database, follow-up data were collected on all patients diagnosed from 2000 to 2003 with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2) normal breast cancer who by nationwide guidelines were treated with 5 year of endocrine therapy (N = 2558)...
January 2018: Acta Oncologica
E J Blok, E Bastiaannet, W B van den Hout, G J Liefers, V T H B M Smit, J R Kroep, C J H van de Velde
Gene expression profiles with prognostic capacities have shown good performance in multiple clinical trials. However, with multiple assays available and numerous types of validation studies performed, the added value for daily clinical practice is still unclear. In Europe, the MammaPrint, OncotypeDX, PAM50/Prosigna and Endopredict assays are commercially available. In this systematic review, we aim to assess these assays on four important criteria: Assay development and methodology, clinical validation, clinical utility and economic value...
January 2018: Cancer Treatment Reviews
Tinne Laurberg, Trine Tramm, Torsten Nielsen, Jan Alsner, Silje Nord, Simen Myhre, Therese Sørlie, Samuel Leung, Cheng Fan, Charles Perou, Karen Gelmon, Jens Overgaard, David Voduc, Aleix Prat, Maggie Chon U Cheang
BACKGROUND: The study of the intrinsic molecular subtypes of breast cancer has revealed differences among them in terms of prognosis and response to chemotherapy and endocrine therapy. However, the ability of intrinsic subtypes to predict benefit from adjuvant radiotherapy has only been examined in few studies. METHODS: Gene expression-based intrinsic subtyping was performed in 228 breast tumors collected from two independent post-mastectomy clinical trials (British Columbia and the Danish Breast Cancer Cooperative Group 82b trials), where pre-menopausal patients with node-positive disease were randomized to adjuvant radiotherapy or not...
January 2018: Acta Oncologica
Hege O Ohnstad, Elin Borgen, Ragnhild S Falk, Tonje G Lien, Marit Aaserud, My Anh T Sveli, Jon A Kyte, Vessela N Kristensen, Gry A Geitvik, Ellen Schlichting, Erik A Wist, Therese Sørlie, Hege G Russnes, Bjørn Naume
BACKGROUND: The aim of this study was to investigate the prognostic value of the PAM50 intrinsic subtypes and risk of recurrence (ROR) score in patients with early breast cancer and long-term follow-up. A special focus was placed on hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) pN0 patients not treated with chemotherapy. METHODS: Patients with early breast cancer (n = 653) enrolled in the observational Oslo1 study (1995-1998) were followed for distant recurrence and breast cancer death...
November 14, 2017: Breast Cancer Research: BCR
Liying Yang, Yunyan Shen, Xiguo Yuan, Junying Zhang, Jianhua Wei
BACKGROUND: Gene expression profiling has led to the definition of breast cancer molecular subtypes: Basal-like, HER2-enriched, LuminalA, LuminalB and Normal-like. Different subtypes exhibit diverse responses to treatment. In the past years, several traditional clustering algorithms have been applied to analyze gene expression profiling. However, accurate identification of breast cancer subtypes, especially within highly variable LuminalA subtype, remains a challenge. Furthermore, the relationship between DNA methylation and expression level in different breast cancer subtypes is not clear...
November 14, 2017: BMC Bioinformatics
Nora Fernandez-Jimenez, Athena Sklias, Szilvia Ecsedi, Vincent Cahais, Davide Degli-Esposti, Antonin Jay, Pierre Benoit Ancey, Hae Dong Woo, Hector Hernandez-Vargas, Zdenko Herceg
Breast cancer (BC) encompasses heterogeneous pathologies with different subtypes exhibiting distinct molecular changes, including those related to DNA methylation. However, the role of these changes in mediating BC heterogeneity is poorly understood. Lowly methylated regions (LMRs), non-CpG island loci that usually contain transcription factor (TF) binding sites, have been suggested to act as regulatory elements that define cellular identity. In this study, we aimed to identify the key subtype-specific TFs that may lead to LMR generation and shape the BC methylome and transcription program...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
Benjamin De Leener, Vladimir S Fonov, D Louis Collins, Virginie Callot, Nikola Stikov, Julien Cohen-Adad
Template-based analysis of multi-parametric MRI data of the spinal cord sets the foundation for standardization and reproducibility, thereby helping the discovery of new biomarkers of spinal-related diseases. While MRI templates of the spinal cord have been recently introduced, none of them cover the entire spinal cord. In this study, we introduced an unbiased multimodal MRI template of the spinal cord and the brainstem, called PAM50, which is anatomically compatible with the ICBM152 brain template and uses the same coordinate system...
October 21, 2017: NeuroImage
Hiroko Masuda, Yuan Qi, Shuying Liu, Naoki Hayashi, Takahiro Kogawa, Gabriel N Hortobagyi, Debu Tripathy, Naoto T Ueno
BACKGROUND: Reverse phase protein array (RPPA) analysis, allows investigation of potential targets at the functional protein level,. We identified TNBC subtypes at the protein level using RPPA and compared them with mRNA molecular subtypes (TNBCtype, TNBCtype-4, and PAM50) that is unique in its availability of both RPPA and mRNA analyses. METHODS: We classified the samples from 80 TNBC patients using both k-means and hierarchical consensus clustering analysis and performed Ingenuity Pathway Analysis...
September 19, 2017: Oncotarget
Masafumi Shimoda, Ami Hori, Jack R Wands, Ryo Tsunashima, Yasuto Naoi, Tomohiro Miyake, Tomonori Tanei, Naofumi Kagara, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
Although prognostic markers for early estrogen receptor (ER)-positive breast cancer have been extensively developed, predictive markers for adjuvant endocrine therapy are still lacking. Focusing on the mechanisms underlying endocrine resistance, we investigated whether the endocrine sensitivity of ER-positive breast cancer cells was correlated with the expression of aspartate-β-hydroxylase (ASPH), which is involved in the development of hepatocellular carcinoma. ASPH expression in ER-positive and tamoxifen-resistant breast cancer cells was upregulated by the MAPK and phosphoinositide-3 kinase (PI3K) pathways, which both play pivotal roles in endocrine resistance...
December 2017: Cancer Science
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