Emmanouil G. SifakisKarolinska Institutet | KI · Department of Oncology-Pathology
Emmanouil G. Sifakis
Doctor of Philosophy (PhD)
About
51
Publications
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647
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Introduction
Additional affiliations
May 2017 - present
October 2013 - April 2017
May 2012 - October 2013
Publications
Publications (51)
Formalin-fixed paraffin-embedded (FFPE) tissue represents a valuable source for translational cancer research. However, the widespread application of various downstream methods remains challenging. Here, we aimed to assess the feasibility of a genomic and gene expression analysis workflow using FFPE breast cancer (BC) tissue. We conducted a systema...
Developing AI models for digital pathology has traditionally relied on single-scale analysis of histopathology slides. However, a whole slide image is a rich digital representation of the tissue, captured at various magnification levels. Limiting our analysis to a single scale overlooks critical information, spanning from intricate high-resolution...
Around 75% of breast cancer (BC) patients have tumors expressing the predictive biomarker estrogen receptor α (ER) and are offered endocrine therapy. One-third eventually develop endocrine resistance, a majority with retained ER expression. Mutations in the phosphatidylinositol bisphosphate 3-kinase (PI3K) catalytic subunit encoded by PIK3CA is a p...
Although metabolic reprogramming within tumor cells and tumor microenvironment (TME) is well described in breast cancer, little is known about how the interplay of immune state and cancer metabolism evolves during treatment. Here, we characterize the immunometabolic profiles of tumor tissue samples longitudinally collected from individuals with bre...
Background: The PREDIX HER2 trial, compared six courses of docetaxel, trastuzumab, and pertuzumab (DTP) vs. trastuzumab emtansine (T-DM1) as neoadjuvant treatment for HER2-positive breast cancer (BC). Similar rates of pathologic complete response (pCR) were seen.
Methods: Clinicopathological, shallow whole-genome sequencing (CUTseq, n=176), whole e...
Background
Around 75% of breast cancer (BC) patients have tumors expressing the treatment-predictive biomarker estrogen receptor α (ER) and are consequently offered endocrine therapy. One-third of these patients develop endocrine resistance, a majority with tumors that retain ER expression. For most cases, the resistance mechanism is still unknown,...
Background: Biological tumor signatures of HER2-positive breast cancer may impact patients’ response to HER2 targeted treatment and are important to investigate since there is a need for both escalation and de-escalation of HER2-directed treatments. We aimed to examine subgroups of HER2-positive tumors based on different biological pathway enrichme...
Background
Breast cancer (BC) is a heterogeneous disease that can be divided into intrinsic molecular subtypes. Among the four intrinsic subtypes, Luminal A and Luminal B are the most common and associated with the best outcome, whereas HER2-enriched and basal-like are less frequent. Tumors that are estrogen receptor α (ER)-positive and human epide...
Background
Overexpression of human epidermal growth factor receptor 2 (HER2) caused by HER2 gene amplification is a driver in breast cancer tumorigenesis. We aimed to investigate the prognostic significance of manual scoring and digital image analysis (DIA) algorithm assessment of HER2 copy numbers and HER2/CEP17 ratios, along with ERBB2 mRNA level...
Introduction: The use of preoperative CDK4/6 inhibitors combined with endocrine treatment remains investigational in breast cancer (BC), while their effect on tumor-immune microenvironment (TIME) in luminal BC is the subject of few published studies. The aim of this study was to characterize the treatment-induced changes of TIME at a spatial proteo...
Background: The PREDIX HER2 trial compared standard neoadjuvant therapy with 6 cycles of docetaxel, trastuzumab, and pertuzumab (DTP), versus 6 cycles of trastuzumab emtansine (T-DM1) in 197 patients with HER2-positive breast cancer. There was no difference in pathologic complete response (pCR) rate and event-free survival (EFS) between the two tre...
Breast cancer (BC) is a complex disease comprising multiple distinct subtypes with different genetic features and pathological characteristics. Although a large number of antineoplastic compounds have been approved for clinical use, patient-to-patient variability in drug response is frequently observed, highlighting the need for efficient treatment...
Background:. Up to 75% of breast cancer patients have tumors expressing the predictive biomarker estrogen receptor alpha (ER) and are consequently offered endocrine therapy. Approximately one third eventually relapse in their disease with the majority still expressing ER but resistant to one or several types of endocrine-based therapies. Molecular...
Background
There is a paucity of data on the prognostic value of programmed cell death protein 1 (PD-1) protein and gene expression in early breast cancer (BC) and the present study’s aim was to comprehensively investigate it.
Methods
The study consisted of three parts: a correlative analysis of PD-1 protein and gene expression from an original pa...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Background: We have previously shown the prognostic value of PD-L1 protein and gene expression in early breast cancer (BC), however, the prognostic role of PD-1 expression remains unclear. Methods: The prognostic value of PD-1 in early BC was investigated using three different approaches: i) evaluation of PD-1 at the protein (IHC, immunohistoch...
Gene and protein expression of Programmed Death Ligand‐1 (PD‐L1) are prognostic in early breast cancer (BC), but their prognostic information is inconsistent at least in some biological subgroups. The validated prognostic gene signatures (GS) in BC are mainly based on proliferation and estrogen receptor (ER)‐related genes. Here we aimed to explore...
Introduction: The SAM domain and HD domain 1 (SAMHD1) protein is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase initially described to restrict human immunodeficiency virus type 1 (HIV-1) in the immune cells through depletion of intracellular dNTP substrates required for HIV-1 replication. Because of its ability to deplete the dNTP pool,...
WNT signaling activates MYC expression in cancer cells. Here we report that this involves an oncogenic super-enhancer-mediated tethering of active MYC alleles to nuclear pores to increase transcript export rates. As the decay of MYC transcripts is more rapid in the nucleus than in the cytoplasm, the oncogenic super-enhancer-facilitated export of nu...
Signal transducer and activator of transcription 3 (STAT3) is an oncogene and multifaceted transcription factor involved in multiple cellular functions. Its role in modifying anti-tumor immunity has been recently recognized. In this study, the biologic effects of STAT3 on immune checkpoint expression and anti-tumor responses were investigated in br...
550
Background: We have previously demonstrated that PD-L1 mRNA expression can serve as prognostic biomarker in breast cancer (BC). In ER+/HER2- BC, RS and 70-gene signature are used to predict the risk of recurrence and benefit from chemotherapy. Methods: Discovery cohort (cohort 1) included 302 patients diagnosed with primary ER+/HER2- BC (1997-2...
Background
Use of cyclin D1 (CCND1) gene amplification as a breast cancer biomarker has been hampered by conflicting assessments of the relationship between cyclin D1 protein levels and patient survival. Here, we aimed to clarify its prognostic and treatment predictive potential through comprehensive long-term survival analyses.
Methods
CCND1 ampl...
Introduction:PD-L1 expression as assessed by immunohistochemistry (IHC) is a clinically relevant biomarker in certain malignancies such as lung cancer, since it selects appropriate candidates for PD-1 blockade. Since these agents are under evaluation for breast cancer, discovering and validating predictive biomarkers is of outmost importance. Howev...
Background/aim:
Little is known about the correlation between contrast-enhanced ultrasound (CEUS) characteristics and pathological prognostic factors in breast cancer. The aim of this study was to explore the correlation between CEUS characteristics and pathological prognostic factors.
Patients and methods:
A retrospective study with 34 malignan...
The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood due to poor sensitivity and/or resolution of current chromatin structure-based assays. Consequently, it is not well established if enhancers operate individually and/or in clusters to coordinate gene transcription. In the current study,...
Transcriptionally active and inactive chromatin domains tend to segregate into separate sub-nuclear compartments to maintain stable expression patterns. However, here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs). The interactome is regulated by PARP1 and i...
Automatic segmentation of the arterial lumen from ultrasound images is an important task in clinical diagnosis. Carotid artery recognition, the first task in lumen segmentation, should be performed in a fully automated, fast, and reliable way to further facilitate the low-level task of arterial delineation. In this paper, a user-independent, real-t...
High-throughput DNA methylation profiling exploits microarray technologies thus providing a wealth of data, which however solicits rigorous, generic, and analytical pipelines for an efficient systems level analysis and interpretation. In this study, we utilize the Illumina's Infinium Human Methylation 450K BeadChip platform in an epidemiological co...
The scope of this study is the identification of gender-independent muscle transcriptional differences between younger and older subjects using skeletal muscle gene expression profiles. Towards this end, a combination of statistical methods, functional analyses, and machine learning techniques were exploited, and applied on an integrative dataset o...
DNA methylation profiling methods exploit microarray technologies and provide a wealth of high-volume data. This data solicits generic, analytical pipelines for the meaningful systems-level analysis and interpretation. In the current study, an intelligent framework is applied, encompassing epidemiological.DNA methylation data produced from the Illu...
DNA methylation events represent epigenetic heritable modifications that regulate gene expression by affecting chromatin remodeling. They are encountered more often in CpG rich promoter regions, while they do not alter the DNA sequence itself. High-volume DNA methylation profiling methods exploit microarray technologies and provide a wealth of data...
In this work, two novel background correction (BC) methods, along with several commonly used ones, are evaluated regarding noise reduction in eleven two-channel self-versus-self (SVS) hybridizations. The evaluation of each BC method is investigated under the use of four statistical criteria combined into a single measure, the polygon area measure....
It has been shown previously that glucocorticoids exert a dual mechanism of action, entailing cytotoxic, mitogenic as well as cell proliferative and anti-apoptotic responses, in a dose-dependent manner on CCRF-CEM cells at 72 h. Early gene expression response implies a dose-dependent dual mechanism of action of prednisolone too, something reflected...
Microarray experimentation has been widely used for screening and high throughput discovery of mechanisms underlying biological systems. However, there are many factors that need to be taken into account for an effective microarray experimental design. Such factors are the abundance of starting material (RNA), number of replicates or experimental c...
It has been shown previously that glucocorticoids exert a dual mechanism of action, meaning cytotoxic and mitogenic as well as mitogenic and anti-apoptotic, in a dose-dependent manner on CCRF-CEM cells at 72 h. Early gene expression response suggested also a dose-dependent dual mechanism of action of prednisolone which is apparently reflected on ce...
The objective of the present study was the analysis of microarray data from a T-cell leukemia cell line (CCRF-CEM), treated with two different prednisolone concentrations, using four different pre-processing methods, within the Matlab<sup>reg</sup> computing environment. We have compared these methods using hierarchical clustering. The gene express...
Automatic segmentation of the arterial lumen from ultrasound images is an important task in clinical diagnosis. In this paper, the Hough transform (HT) was used to automatically extract straight lines and circles from sequences of B-mode ultrasound images of longitudinal and transverse sections, respectively, of the carotid artery. In 10 normal sub...
The objective of the present study is the prediction of fetal acidemia based on the Very Low Frequency (VLF) components of the Fetal Heart Rate (FHR) and Fetal Pulse Oximetry (FspO2) recordings during labor. In order to perform the spectral analysis, we applied the Continuous Wavelet Transform (CWT) and the adaptive approximation technique using th...