Project description:In this study we generated gene expression profiles of 41 and 55 samples of patients with and without inflammatory breast cancer (IBC vs. non-IBC). The aim of the study was to delineate the specific transcriptional profile of the samples from patients with IBC in search for diagnostic, prognostic and predictive biomarkers.
Project description:We profile single cells from patients with colorectum cancer using Chromium 3’ and 5’ single-cell RNA-sequencing. Patients EXT001, EXT009, and EXT012 from the KUL dataset were first analyzed by Lee et al., 2020, and the raw data are available in ArrayExpress under the accession codes E-MTAB-8410 and E-MTAB-8107. Patients EXT018, EXT048, EXT113, and EXT121 from KUL dataset were previously analyzed by Joanito et al., 2022. The raw data of those patients are available in EGA under the accession codes EGAD00001008584 and EGAD00001008585.
Project description:Inflammatory breast cancer (IBC) is a rare and aggressive subtype of breast cancer (BC) that regularly affects women younger than 40 years and accounts for 1 to 5% of all types of BC. There is not an optimal treatment for women with IBC. Approximately 40% of IBC patients are HER2+, which can be treated with the monoclonal antibody-based therapy, Herceptin (trastuzumab). However, more than 25% of patients become resistant to trastuzumab-based therapy in early stages and about 75% in late stages patients and effective second line targeted therapies are currently unavailable for IBC patients. Lipocalin-2 (LCN2) is a is a secreted protein involved in iron homeostasis, immune responses, transportation of siderophores for degradation, and epithelial cell differentiation. LCN-2 is highly abundant in certain subtypes of aggressive cancers including IBC. Reports have shown that LCN-2 is a potential target therapy for IBC patients. Here, we developed a double targeted therapy of liposomal-Herceptin formulation loaded with LCN2-targeted small interference RNA (siRNA). Trastuzumab DSPE-PEG(2000)-maleimide conjugates were synthesized for liposomal formulation, resulting in sizes of 18.3 nm and 73.7 nm for free DSPE-PEG(2000)-trastuzumab and trastuzumab-liposome, respectively. This formulation was efficiently internalized into HER2+ IBC cells, and reduced cell proliferation and tumor emboli formation in IBC cells. To further understand the molecular mechanism downstream LCN-2, we performed RNA-sequencing (RNA-seq), and we identified 139 differentially expressed genes upon siRNA-mediated LCN-2 knockdown in IBC cells. Ingenuity Pathway Analysis grouped the RNA-seq data into 25 canonical pathways altered downstream LCN-2. Together, this information suggests that LCN2-target siRNA within Herceptin-conjugated liposomes is a potential therapeutic strategy against IBC.
Project description:Inflammatory breast cancer (IBC), the most aggressive and lethal breast cancer subtype, lacks unequivocal genomic differences or robust biomarkers that differentiate it from non-IBC. Here, Thermostable Group II Intron Reverse Transcriptase sequencing of RNA samples revealed myriad differences in tumors, PBMCs, and plasma that distinguished IBC from non-IBC patients and healthy donors across all tested non-IBC subtypes. By mapping reads to genome and transcriptome reference sequences and quantitating intron-to-exon read depth ratios, we developed methods for parallel analysis of transcriptional and post-transcriptional gene regulation. This analysis identified numerous protein-coding genes in IBC patient tumors and PBMCs with high intron-to-exon read depths, suggesting rate-limiting RNA splicing that negatively impacts mRNA production. Mirroring gene expression differences in tumors and PBMCs, over-represented protein-coding gene RNAs in IBC patient plasma were largely intron RNA fragments, while those in non-IBC patient and healthy donor plasma were largely mRNA fragments. Our findings provide new insights into IBC and should enable monitoring disease progression by liquid biopsy.
Project description:This single cell RNA-seq experiment was performed to quantify DLL3 expression in circulating tumor cells in small cell lung cancer patients to predict response to tarlatamab treatment. CTCs enriched from the blood of three SCLC patients prior or post tarlatamab treatment using the CTC-iChip followed by magnetic depletion of RBCs were processed with the 10x Genomics Chromium platform (Chromium GEM-X Single Cell 3' Kit v4) and sequenced on a NextSeq 2000 system. Corresponding EGA study number: EGAS50000001401, EGA dataset number: EGAD50000002035
Project description:By generating a paired single cell RNA-sequencing database of the tumor niche from 10 newly diagnosed MM patients, we created a unique dataset allowing the in-depth analyses of stromal-immune interactions within the tumor microenvironment (see related accession number). Using this database, we identified the presence of inflammatory stromal fibroblasts in the bone marrow of Myeloma patients.The stromal inflammation was associated with NF-κB signaling, and sources of IL-1β or TNFα were specific immune subsets previously shown to be altered in MM, suggesting the presence of an immune cell-mediated feed-forward loop of bone marrow inflammation in MM. By tracking inflammatory signatures over time in individual patients undergoing first-line treatment using bulk RNA sequencing, we show that bone marrow inflammation is not reverted by successful anti-tumor therapy (this dataset), suggesting a role for stromal fibroblasts and bone marrow inflammation in disease persistence or relapse. Raw sequencing data files will be deposited to EGA.
Project description:In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (both coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett’s esophagus. Per patient, a blood plasma sample, and a healthy esophageal and disease tissue sample were included. In total, this comprehensive dataset consists of 102 RNA-seq libraries from 51 samples. The raw data for this study have been deposited to the controlled access archive EGA under submission EGAS00001004939.
Project description:In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (both coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett’s esophagus. Per patient, a blood plasma sample, and a healthy esophageal and disease tissue sample were included. In total, this comprehensive dataset consists of 102 RNA-seq libraries from 51 samples. The raw data for this study have been deposited to the controlled access archive EGA under submission EGAS00001004939.
Project description:In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (both coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett’s esophagus. Per patient, a blood plasma sample, and a healthy esophageal and disease tissue sample were included. In total, this comprehensive dataset consists of 102 RNA-seq libraries from 51 samples. The raw data for this study have been deposited to the controlled access archive EGA under submission EGAS00001004939.
Project description:In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (both coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett’s esophagus. Per patient, a blood plasma sample, and a healthy esophageal and disease tissue sample were included. In total, this comprehensive dataset consists of 102 RNA-seq libraries from 51 samples. The raw data for this study have been deposited to the controlled access archive EGA under submission EGAS00001004939.