Single-cell dissection of multifocal bladder cancer reveals malignant and immune cells variation between primary and recurrence tumor lesions
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE277524 | GEO | 2024/11/15
REPOSITORIES: GEO
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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
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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 | GSE112790 | GEO
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 | GSE113017 | GEO
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 | GSE112788 | GEO
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2018-07-04 | PXD006805 | Pride
Project description:Recent findings suggested a benefit of anti-EGFR therapy for basal-like muscle invasive bladder cancer (MIBC). However, impact on bladder cancer with substantial squamous differentiated (Sq-BLCA) and especially pure squamous cell carcinoma (SCC) remains unknown. Therefore, we comprehensively characterized pure and mixed Sq-BLCA (n=125) on genetic and protein expression level, and performed functional pathway and drug-response analyses with cell line models and isolated primary SCC (p-SCC) cells of the human urinary bladder. We identified abundant EGFR expression in 95% of Sq-BLCA without evidence for activating EGFR mutations. Both SCaBER and p-SCC cells were sensitive to EGFR tyrosine kinase inhibitors (TKIs: erlotinib and gefitinib). Combined treatment with anti-EGFR TKIs and varying chemotherapeutics led to a concentration-dependent synergism in SCC cells according to the Chou-Talalay method. In addition, siRNA knockdown of EGFR impaired SCaBER viability suggesting a putative ‘‘Achilles heel’’ of Sq-BLCA. The observed effects seem Sq-BLCA-specific since non-basal urothelial cancer cells were characterized by poor TKI sensitivity associated with a short-term feedback response by upregulating EGFR and ERBB3 expression. Hence, our findings give novel insights into a crucial, Sq-BLCA-specific role of the ERBB signaling pathway proposing improved effectiveness of combined anti-EGFR and chemotherapeutic regimens in squamous bladder cancers with wild-type EGFR-overexpression.
2023-03-12 | GSE146975 | GEO
Project description:Purpose: Several risk factors for local recurrence of breast cancer after breast conserving therapy (BCT) have been identified. The identification of additional risk factors would be very useful in guiding optimal therapy and also improve understanding of the mechanisms underlying local recurrence. We used cDNA microarray analysis to identify gene expression profiles associated with local recurrence. Experimental Design: Using 18K cDNA microarrays, gene expression profiles were obtained from 50 patients who underwent BCT. Of these 50 patients 19 developed a local recurrence; the remaining 31 patients were selected as controls as they were free of local recurrence at least 11 years after treatment. For 9/19 patients also the local recurrence was available for gene expression profiling. Unsupervised and supervised methods of classification were used to separate patients in groups corresponding to disease outcome and to study the overall gene expression pattern of primary tumors and their recurrences. Results: Hierarchical clustering of patients did not show any grouping reflecting local recurrence status. Supervised analysis revealed no significant set of genes that was able to distinguish recurring tumors from non-recurring tumors. Paired-data analysis of primary tumors and local recurrences showed a remarkable similarity in gene expression profile between primary tumors and their recurrences. Conclusions: No significant differences in gene expression between primary breast cancer tumors in patients with or without local recurrence after breast conserving therapy were identified. Furthermore, analyses of primary tumors and local recurrences show a preservation of the overall gene expression pattern in the local recurrence, even after radiotherapy. Keywords: gene expression profiling
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