Single-cell dissection of multifocal bladder cancer reveals malignant and immune cells variation between primary and recurrence tumor lesions
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ABSTRACT:
PROVIDER: PRJNA1162642 | ENA |
REPOSITORIES: ENA
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Project description:Bladder carcinoma (BLCA) is characterized by a high rate of post-surgery relapse and multifocality, with multifocal tumors carrying a 40% higher risk of recurrence compared to single tumors. Recurrence is a major contributor to bladder cancer-specific mortality. However, understanding interregional or intraregional malignant heterogeneity and cellular communication within the primary and recurrence tumor microenvironment (TME) remains a significant challenge. Here, we employed single-cell RNA sequencing (scRNA-seq) to analyze separate tumor lesions from five multifocal bladder cancer patients (comprising three primary tumors and two recurrence tumors).
2024-11-15 | GSE277524 | GEO
Project description:An evaluation of multifocal lesions from patients with in-transit extremity melanoma to determine if all lesions from a patient harbor homogeneous patterns of gene expression; Gene expression profiling studies can help guide treatment for cancer patients by providing tools in the form of gene-expression signatures to characterize a tumor in terms of underlying biology, predicted response to therapy, metastatic progression and/or recurrence. The utility of gene signatures for defining therapeutic strategies in the treatment of extremity in-transit melanoma will be dependent on the genetic relationship between the multifocal lesions typically present in this disease and the extent to which a single lesion is representative of residual tumor burden. Using microarray-based gene expression profiling we examined 43 in-transit melanoma lesions across 17 patients with multifocal disease to determine whether one lesion could accurately characterize the underlying biology and genetic profile of a patient's tumor. Principal component analysis, unsupervised hierarchical clustering, one-way analysis of variance (ANOVA) and gene signatures predictive of chemosensitivity and oncogenic pathway activation showed gene expression patterns to be highly similar (p-values: <0.006; average r = 0.979) between lesions from a single patient but to be significantly different across patients (p<0.05). These findings demonstrate that individual melanoma tumor nodules in patients with multifocal disease are genetically similar and a single lesion can be used to predict response to chemotherapy, evaluate the activation status of oncogenic signaling pathways and characterize other aspects of the biology of an individual patient's disease. These results will facilitate the utilization of gene expression profiling in clinical trials of targeted therapy in melanoma allowing for more rational identification of candidates for specific therapies. Experiment Overall Design: Gene expression profiles were obtained from 43 lesions across 17 patients and evaluated using several different algorithms to determine the degree of correlation across multifocal lesions and to evaluate patterns of gene expression that are different across patients
2008-11-13 | E-GEOD-10282 | biostudies-arrayexpress
Project description:A significant proportion of breast cancer patients develop multiple synchronous unilateral breast tumors, also referred to as multifocal tumors, which represent a diagnostic and therapeutic challenge. Multifocality has been associated with a possible adverse patient outcome, propensity for axillary nodal involvement, and increased risk of local recurrence following breast conserving surgery when compared to unifocal tumors. Previous studies indicate that most lesions from multifocal tumors are concordant with regard to the currently used pathological parameters (histological subtype and grade, hormonal receptors and HER2 status). However, to our knowledge, no study has yet provided a detailed molecular analysis of multifocal breast cancer. Here, we aimed to better define the incidence of multifocal breast cancer using a systematic analysis of pathology reports of primary breast cancers and to compare different foci from 5 multifocal breast cancers in a global analysis using genomic, transcriptomic and epigenomic data. We demonstrate that multifocality is a frequent finding since it concerns 22% (945/4340) of breast cancer patients with primary ductal breast cancer. We find that different lesions from multifocal breast cancer can differ at the (epi)genomic and transcriptomic level even when the foci present similar histology, grading, hormonal and HER2 status despite having a common genetic background. Since the number of (epi)genetic alterations with potential clinical utility is rapidly growing due to increasing numbers of targeted therapies, these findings suggest that it might be necessary to interrogate the different lesions of multifocal breast cancers for adequate treatment management of these tumors. The biological characterization of multifocal breast cancer here is focused on 5 cancers for which the foci did not differ in terms of histological grade, hormonal receptors and HER2 status. The characterization of multifocal tumors involved the identification of somatic rearrangements in 2 foci from each patient via low-coverage whole genome sequencing. Putative rearrangements were amplified by polymerase chain reaction (PCR) and capillary sequenced in tumor and matching blood-derived germline DNA to validate the somatic rearrangements. For all patients, the presence of a number of validated rearrangements was assessed in different paraffin blocks of tumor-adjacent histologically normal tissue by nested PCR. We also performed transcriptomic and epigenomic profiling in 4 and 5 patients respectively using the HG-U133 Plus 2.0 Chips and Infinium Methylation 450K arrays (RNA was not available for patient E).
2018-12-21 | GSE39451 | GEO
Project description:Expression profiling of superficial bladder tumours to delineate the expression pattern differences between non-recurring and recurring tumours. Keywords = bladder cancer, superficial, recurrence, prediction Keywords: other
2002-12-08 | GSE88 | GEO
Project description:Genome-scale DNA methylation profiling using the Infinium DNA methylation 450K BeadChip platform and samples from gastric cancer (intestinal and diffuse), precursor lesions (multifocal chronic atrophic gastritis and inestina metaplasia), non-atrophic gastritis and normal gastric mucosa.
2021-03-04 | GSE127857 | GEO
Project description:Although non muscle-invasive bladder cancer can be treated successfully by surgical resection, there is a high rate of recurrence, which frequently develops into an invasive form of cancer. Due to the lack of marker molecules to predict recurrence, it is currently recommended that after resection each patient is screened via cystoscopy at least twice a year. This results in a psychic burden to the patient and substantial economic costs to the health care system. Using antibody microarrays targeting 724 different cancer-related proteins, we studied protein profiles of patients with and without recurrence. The analysis revealed 255 proteins of differential abundance. Most are involved in the regulation and execution of apoptosis and cell proliferation. For prognosis, a signature of 20 proteins was determined that predicts bladder cancer recurrence with 100% sensitivity and 80% specificity. As a measure of overall accuracy, the area under the curve (AUC) value was found to be 90%. This is well within a clinically relevant window of quality and should support decision making about the stringency of surveillance or even different treatment options.
2014-04-07 | E-MEXP-3625 | biostudies-arrayexpress
Project description:Compare the efficacy and safety of endoscopic resection a full thickness (EFTR) with Full Thickness Resection Device (FTRD) System versus endoscopic submucosal dissection (ESD) in the treatment of Laterally Spreading Tumor Non Granular Type (LST-NG), "no lift" lesions colon and residual / relapse on scars from previous resections endoscopic colon. The dimensional cut off of these lesions is ≤30mm
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Project description:Hepatocellular carcinoma (HCC) is a heterogeneous disease with a variety of etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multifocal recurrence. Comprehensive molecular evaluation of HCC by multiplatform analysis defined three major subtypes: (1) mitogenic and stem cell-like tumors with chromosomal instability; (2) CTNNB1-mutated tumors displaying DNA hypermethylation; and (3) metabolic syndrome-associated tumors, which included an immunogenic subgroup characterized by macrophage infiltration and favorable prognosis. Although genomic and epigenomic analysis explicitly discriminated HCC with intrahepatic metastasis (IM) from multicentric HCC (MC), the phenotypic similarity between the primary and recurrent tumors was not linked to the IM/MC diagnosis, but rather the integrated classification. Thus, identification of these HCC subtypes provides insights into patient stratification and opportunities for therapeutic development.
2019-01-03 | GSE113019 | GEO
Project description:An evaluation of multifocal lesions from patients with in-transit extremity melanoma to determine if all lesions from a patient harbor homogeneous patterns of gene expression Gene expression profiling studies can help guide treatment for cancer patients by providing tools in the form of gene-expression signatures to characterize a tumor in terms of underlying biology, predicted response to therapy, metastatic progression and/or recurrence. The utility of gene signatures for defining therapeutic strategies in the treatment of extremity in-transit melanoma will be dependent on the genetic relationship between the multifocal lesions typically present in this disease and the extent to which a single lesion is representative of residual tumor burden. Using microarray-based gene expression profiling we examined 43 in-transit melanoma lesions across 17 patients with multifocal disease to determine whether one lesion could accurately characterize the underlying biology and genetic profile of a patient's tumor. Principal component analysis, unsupervised hierarchical clustering, one-way analysis of variance (ANOVA) and gene signatures predictive of chemosensitivity and oncogenic pathway activation showed gene expression patterns to be highly similar (p-values: <0.006; average r = 0.979) between lesions from a single patient but to be significantly different across patients (p<0.05). These findings demonstrate that individual melanoma tumor nodules in patients with multifocal disease are genetically similar and a single lesion can be used to predict response to chemotherapy, evaluate the activation status of oncogenic signaling pathways and characterize other aspects of the biology of an individual patient's disease. These results will facilitate the utilization of gene expression profiling in clinical trials of targeted therapy in melanoma allowing for more rational identification of candidates for specific therapies. Keywords: Disease state analysis
2008-10-30 | GSE10282 | GEO
Project description:Helicobacter pylori infection triggers a cascade of inflammatory stages that may lead to the appearance of non-atrophic gastritis, multifocal atrophic gastritis, intestinal metaplasia, dysplasia, and cancer. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of secreted scavenger receptor cysteine-rich proteins and is considered to be involved in host defense by binding to pathogens. Recent studies have shown that DMBT1 expression is up-regulated in areas of intestinal metaplasia and in gastric tumors. Here, we examined the role of DMBT1 in the development of inflammatory response and gastric precancerous lesions in Caucasian, African American and Hispanic populations as well as in a mouse model. We found that mucosal DMBT1 expression is significantly increased in individuals with more advanced gastric precancerous lesions. We also show that H. pylori infection of Dmbt1-/- mice results in enhanced gastric inflammation and the development of mucous metaplasia that is accompanied by increased cell proliferative rates and reduced IL-33 expression levels in the inflamed mucosa. Taken together, our data suggest that DMBT1 may be mediating mucosal protection that may reduce the risk of developing gastric precancerous lesions in response to H. pylori infection
2017-06-30 | GSE83389 | GEO