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Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma

ABSTRACT: Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma

PROVIDER: PRJNA704753 | ENA |

REPOSITORIES: ENA

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Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma

Project description:Esophageal squamous cell carcinoma (ESCC) remains one of the most deadly cancer types worldwide. Comprehensively dissecting the molecular characterization of ESCC paves the way for developing more promising therapeutics. Here, we performed RNA-seq and ATAC-seq on three pairs of ESCC tumor tissues and patient-matched adjacent normal tissues.

2021-02-25 | GSE167488 | GEO

Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma.

Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) remains one of the deadly cancer types. Comprehensively dissecting the molecular characterization and the heterogeneity of ESCC paves the way for developing more promising therapeutics.MethodsExpression profiles of multiple ESCC datasets were integrated. ATAC-seq and RNA-seq were combined to reveal the chromatin accessibility features. A prognosis-related subtype classifier (PrSC) was constructed, and its association with the tumor microenvironment (TME) and immunotherapy was assessed. The key gene signature was validated in clinical samples. Based on the TME heterogeneity of ESCC patients, potential subtype-specific therapeutic agents were screened.FindingsThe common differentially expressed genes (cDEGs) in ESCC were identified. Up-regulated genes (HEATR1, TIMELESS, DTL, GINS1, RUVBL1, and ECT2) were found highly important in ESCC cell survival. The expression alterations of PRIM2, HPGD, NELL2, and TFAP2B were associated with chromatin accessibility changes. PrSC was a robust scoring tool that was not only associated with the prognosis of ESCC patients, but also could reflect the TME heterogeneity. TNS1high fibroblasts were associated with immune exclusion. TG-101348 and Vinorelbine were identified as potential subtype-specific therapeutic agents. Besides, the application of PrSC into two immunotherapy cohorts indicated its potential value in assessing treatment response to immunotherapy.InterpretationOur study depicted the multi-dimensional characterization of ESCC, established a robust scoring tool for the prognosis assessment, highlighted the role of TNS1high fibroblasts in TME, and identified potential drugs for clinical use.FundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

| S-EPMC8353400 | biostudies-literature

Three-Dimensional Tumor Profiling Reveals Minimal mRNA Heterogeneity in Esophageal Squamous Cell Carcinoma

Project description:We microdissected discrete sub-regions of esophageal squamous cell carcinoma (ESCC) and analyzed the transcriptomes throughout three-dimensional (3D) tumor space.

2011-11-04 | GSE33426 | GEO

Three-Dimensional Tumor Profiling Reveals Minimal mRNA Heterogeneity in Esophageal Squamous Cell Carcinoma

Project description:We microdissected discrete sub-regions of esophageal squamous cell carcinoma (ESCC) and analyzed the transcriptomes throughout three-dimensional (3D) tumor space. Nine cases were used for TP/TC comparison, five cases were used for 3D analysis, one normal case was set as a control.

2011-11-04 | E-GEOD-33426 | biostudies-arrayexpress

Using gene chip technology to screen invasion related molecular targets of esophageal cancer cell lines

Project description:By using gene chip technology, we can screen esophageal cancer invasion associated genes to understand esophageal squamous carcinoma invasion related mechanisms. Using the Transwell invasion chamber technology to establish human esophageal squamous carcinoma Eca109 and Eca109 - T4 cell lines with different invasion ability. Extracting Eca109 and Eca109-T4 total RNA, reverse transcribed into cDNA probes which labeled with Cy5 and Cy3 fluorescence, then it were hybridized with the Affymetrix gene chip. Using the Genechip- Scanner 3000 scan hybridization signal, and using the SAM 3.0 software analysis and process data.

2014-01-14 | E-GEOD-54041 | biostudies-arrayexpress

Elafin as a Prognostic Marker in Esophageal Squamous Cell Carcinoma: A Pilot Study using Three-Dimensional Imag-ing and Genomic Profiling

Project description:Esophageal cancers are globally the sixth deadliest malignancy, with limited curative options. The association of high serum elafin levels, a molecule produced by epithelial cells, with esophageal squamous cell carcinoma (ESCC) risk is established, but its link to poor ESCC prognosis remains unclear. To explore this question, we first used three-dimensional confocal imaging to create a model of the spatial distribution of elafin inside locoregional ESCC tissues. Then, after analyzing data ob-tained from whole-genome microarrays for ESCC cell lines and their more invasive sublines, we performed in vitro experiments using RNA sequencing to identify possible elafin-related pathways. Three-dimensional tissue imaging showed elafin distributed as an interweaved-like fibrous structure in the stroma of tissue obtained from patients with high serum levels of elafin and poorer prognoses. By contrast, the signal was confined inside or around the tumor nest in patients who had lower serum levels and better survival. The analysis of a TCGA dataset revealed that higher levels of elafin mRNA in stage I–IIIA ESCC patients were associated with shorter survival. The in vitro studies revealed that elafin promoted ESCC cell proliferation, migration, and invasion via the epithelial–mesenchymal transition pathway. Thus, elafin inhibition could potentially be used therapeutically to improve survival in patients with locoregional ESCC.

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Human esophageal dysplasia (16 cases) vs. esophageal squamous cell carcinoma (59 cases)

Project description:Our aim is to identify frequent genomic aberrations both in ESCC and esophageal dysplasia, and to discover important copy number-driving genes and microRNAs in ESCC. We carried out array-based comparative genomic hybridization (array CGH) on 59 ESCC resection samples and 16 dysplasia biopsy samples. Expression of genes at 11q13.3 was analyzed by real-time PCR and immunohistochemistry (IHC). Integrated analysis was performed to identify genes or microRNAs with copy number-expression correlations. Two group experiment, esophageal dysplasia vs. esophageal squamous cell carcinoma. Biological replicates: 16 dysplasias vs. 59 carcinomas

2013-04-29 | E-GEOD-46452 | biostudies-arrayexpress

Gene expression profiles of esophageal squamous cell carcinoma cell lines

Project description:Profiles of esophageal squamous cell carcinoma and normal esophageal normal epithelium normal cell line. Analysis provides validation of novel microRNA targets prediction algorithms. esophageal squamous cell carcinoma:14, normal epithelium cell:2

2016-09-01 | E-GEOD-23964 | biostudies-arrayexpress

Expression data from esophageal squamous cell carcinomas and normal esophageal epithelia

Project description:Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve esophageal squamous cell carcinoma (ESCC) patientsM-bM-^@M-^Y survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could predict CRT response. We aim to identify mRNA markers for ESCC CRT-response prediction through gene expression analyses. Gene expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery and 10 normal esophageal epithelia using Affymetrix U133 Plus 2.0 arrays.

2014-08-01 | E-GEOD-45670 | biostudies-arrayexpress

Gene expression in normal and tumoral esophageal squamous cell lines

Project description:This study was designed to identify genes aberrantly expressed in esophageal squamous cell carcinoma (ESCC) cells. Three esophageal squamous cell carcinoma-derived cell lines and one normal human esophageal squamous cell line were analyzed.

2014-09-20 | E-GEOD-61587 | biostudies-arrayexpress

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