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RNA sequencing revealed the multi-stage transcriptome transformations during the development of gallbladder cancer associated with chronic inflammation

ABSTRACT: RNA sequencing revealed the multi-stage transcriptome transformations during the development of gallbladder cancer associated with chronic inflammation

PROVIDER: PRJNA836273 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19139546_1.fastq.gz	Fastqsanger.gz
	SRR19139546_2.fastq.gz	Fastqsanger.gz
	SRR19139547_1.fastq.gz	Fastqsanger.gz
	SRR19139547_2.fastq.gz	Fastqsanger.gz
	SRR19139548_1.fastq.gz	Fastqsanger.gz

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RNA sequencing revealed the multi-stage transcriptome transformations during the development of gallbladder cancer associated with chronic inflammation

Project description:Purpose Gallbladder cancer (GBC) is a highly malignant tumor with extremely poor prognosis. Previous studies have suggested that the carcinogenesis and progression of GBC is a multi-stage and multi-step process, but most of them focused on the genome changes. And a few studies just compared the transcriptome differences between tumor tissues and adjacent noncancerous tissues. The transcriptome changes, relating to every stage of GBC evolution, have rarely been studied. Methods We selected three cases of normal gallbladder, four cases of gallbladder with chronic inflammation induced by gallstones, five cases of early GBC, and five cases of advanced GBC, using next-generation RNA sequencing to reveal the changes in mRNAs and lncRNAs expression during the evolution of GBC. Results In-depth analysis of the sequencing data indicated that transcriptome changes from normal gallbladder to gallbladder with chronic inflammation were distinctly related to inflammation, lipid metabolism, and sex hormone metabolism; transcriptome changes from gallbladder with chronic inflammation to early GBC were distinctly related to immune activities and connection between cells; and the transcriptome changes from early GBC to advanced GBC were distinctly related to transmembrane transport of substances and migration of cells. Conclusion Expression profiles of mRNAs and lncRNAs change significantly during the evolution of GBC, in which lipid-based metabolic abnormalities play an important promotive role, inflammation and immune activities play a key role, and changes in membrane proteins are the most highlighted molecular changes.

2022-05-31 | GSE202479 | GEO

RNA sequencing revealed the multi-stage transcriptome transformations during the development of gallbladder cancer associated with chronic inflammation.

Project description:Gallbladder cancer (GBC) is a highly malignant tumor with extremely poor prognosis. Previous studies have suggested that the carcinogenesis and progression of GBC is a multi-stage and multi-step process, but most of them focused on the genome changes. And a few studies just compared the transcriptome differences between tumor tissues and adjacent noncancerous tissues. The transcriptome changes, relating to every stage of GBC evolution, have rarely been studied. We selected three cases of normal gallbladder, four cases of gallbladder with chronic inflammation induced by gallstones, five cases of early GBC, and five cases of advanced GBC, using next-generation RNA sequencing to reveal the changes in mRNAs and lncRNAs expression during the evolution of GBC. In-depth analysis of the sequencing data indicated that transcriptome changes from normal gallbladder to gallbladder with chronic inflammation were distinctly related to inflammation, lipid metabolism, and sex hormone metabolism; transcriptome changes from gallbladder with chronic inflammation to early GBC were distinctly related to immune activities and connection between cells; and the transcriptome changes from early GBC to advanced GBC were distinctly related to transmembrane transport of substances and migration of cells. Expression profiles of mRNAs and lncRNAs change significantly during the evolution of GBC, in which lipid-based metabolic abnormalities play an important promotive role, inflammation and immune activities play a key role, and membrane proteins are very highlighted molecular changes.

| S-EPMC10062614 | biostudies-literature

Whole exome sequencing of human tumours and cell lines to investigate how ERBB2 and KRAS Alterations mediate response to EGFR inhibitors in early stage Gallbladder Cancer

Project description:Purpose: The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. The development of new and effective treatment has been and continues to be a major public health imperative. Methods: We report mutational and copy number analysis of 44 predominantly early-staged gallbladder tumors and 5-gallbladder cancer cell lines by a combination of directed and whole exome sequencing at an average coverage of 100X and above. Using gallbladder cancer cell lines and xenograft mouse models we performed phospho-proteome array profiling, followed by an in-depth functional characterization. Results: We describe recurrent activating ERBB2 somatic mutation in 6 of 44 gallbladder primary tumors with an overall mutation frequency of 13%, along with KRAS activating mutations in 3 of 44 samples. Consistent with whole exome findings, a phospho-proteomic array profile of 49-tyrosine kinase revealed constitutive phosphorylation of ERBB2 and EGFR that were found to heterodimerize. We demonstrate that treatment with ERBB2-specific, EGFR-specific shRNA or with covalent EGFR family inhibitor BIBW-2992 inhibits transformation, survival, migration, invasion, and tumor forming characteristics of gallbladder cancer cells harboring wild type or KRAS (G13D) but not KRAS (G12V) mutation. Furthermore, we show in vivo reduction in tumor size is paralleled by a reduction in the amounts of phospho-ERK in KRAS (G13D) but not in KRAS (G12V) xenografts, validating the in vitro findings Conclusion: Findings from this study implicate ERBB2 as an important therapeutic target in early stage gallbladder cancer. We also present the first evidence that the presence of KRAS (G12V), but not KRAS (G13D) mutation, may preclude gallbladder cancer patients to respond to anti-EGFR treatment, similar to the clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer.

2018-12-29 | E-MTAB-6619 | biostudies-arrayexpress

microRNAseq of primary human gallbladder cells, reprogrammed human gallbladder cells, and human pancreatic beta cells

Project description:We determined the global microRNA expression profiles of primary human gallbladder cells and genetically reprogrammed human gallbladder cells and compared with pancreatic beta cells to ascertain the degree of cellular transdifferentatiation of insulin-producing human gallbladder cells to become beta-like cells. First, we cultured patient-derived gallbladder cells and then we transduced these with beta cell transcription factors to reprogram gallbladder cells to become beta-like cells. We used a pan-islet surface monoclonal antibody to enrich for insulin-producing reprogrammed human gallbladder cells using FACS.

2017-08-02 | E-MTAB-5554 | biostudies-arrayexpress

RNAseq of primary human gallbladder cells, reprogrammed human gallbladder cells, and human pancreatic beta cells

Project description:We determined the global gene expression profiles of primary human gallbladder cells and genetically reprogrammed human gallbladder cells and compared with pancreatic beta cells to ascertain the degree of cellular transdifferentatiation of insulin-producing human gallbladder cells to become beta-like cells. First, we cultured patient-derived gallbladder cells and then we transduced these with beta cell transcription factors to reprogram gallbladder cells to become beta-like cells. We used a pan-islet surface monoclonal antibody to enrich for insulin-producing reprogrammed human gallbladder cells using FACS.

2017-08-02 | E-MTAB-5556 | biostudies-arrayexpress

Chronic Salmonella Infection Contributes to Gallbladder Carcinogenesis by Host Epigenetic Modifications

Project description:The present study aimed to understand the pathways involved in gallbladder cancer through genome-wide expression profiling (microarray) of human GBC

2025-02-06 | GSE255497 | GEO

RNA-Sequencing results of the human Gallbladder cancer (GBC) and adjacent tumor tissues (AT)

Project description:Here we report gene expression profiles of human gallbladder cancer (GC) and adjacent tumor (AT) tissues. This study revealed genes with significant changes in gallbladder cancer tissue, providing a basis for exploring the malignant progression of gallbladder cancer.

2025-06-16 | GSE276931 | GEO

Methylation analysis of Chilean patients with gallstone disesase, low- or high-grade gallbladder dysplasia or gallbladder cancer

Project description:Epigenome-wide methylation levels were measured in patients from Chiel with gallstone disease, gallbladder dyplasia or gallbladder cancer using Illumina Infinium methylation arrays.

2020-12-12 | E-MTAB-9868 | biostudies-arrayexpress

Quantitative proteomic analysis of gallbladder cancer

Project description:We carried out an iTRAQ-based quantitative proteomic analysis of gallbladder cancer and adjacent non-tumor tissue to systematically identify differentially expressed proteins in gallbladder cancer. Ten gallbladder adenocarcinoma and ten adjacent non-tumor tissue samples were selected post pathological confirmation for the study. Samples were pooled and In-solution trypsin digestion was carried out. Post digestion, peptides were iTRAQ labeled with 114 and 115 (gallbladder adenocarcinoma) and 116 and 117 (adjacent non-tumor samples). LC-MS/MS analysis of SCX fractions was carried out using a reversed phase analytical C18 column connected to 1200 Series Nanoflow LC interfaced with LTQ-Orbitrap Velos. Data were acquired using Xcalibur 2.1. Proteome Discoverer (v 1.3) suite was used for quantitation and database searches. LC-MS/MS data were searched using Mascot and SEQUEST search algorithms against Human RefSeq 50 supplemented with frequently observed contaminants.

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The gene expression profiles of gallbladder cancer

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