Next Generation Sequencing Facilitates Quantitative Analysis of CAFR and CAFS Transcriptomes in pancreatic cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE192907 | GEO | 2022/01/06
REPOSITORIES: GEO
Similar Datasets
Project description:Pancreatic ductal adenocarcinoma (PDAC) has a characteristically dense stroma comprised predominantly of cancer associated fibroblasts (CAFs). CAFs promote tumor growth, metastasis and treatment resistance. We aimed to investigate the molecular changes and functional consequences associated with chemotherapy treatment of PDAC CAFs. Chemoresistant immortalized CAFs (R-CAFs) were generated by continuous incubation in 100nM gemcitabine. Gene expression differences between treatment naïve CAFs (N-CAFs) and R-CAFs were compared by array analysis. Immortalized human pancreatic CAFs were grown for 30 days in either control media or media containing 100nM gemcitabine. RNA was then isolated and hybidized on U133 Plus 2.0 Affymetrix arrays.
2016-03-09 | E-GEOD-78982 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) has a characteristically dense stroma comprised predominantly of cancer associated fibroblasts (CAFs). CAFs promote tumor growth, metastasis and treatment resistance. We aimed to investigate the molecular changes and functional consequences associated with chemotherapy treatment of PDAC CAFs. Chemoresistant immortalized CAFs (R-CAFs) were generated by continuous incubation in 100nM gemcitabine. Gene expression differences between treatment naïve CAFs (N-CAFs) and R-CAFs were compared by array analysis.
2016-03-09 | GSE78982 | GEO
Project description:Purpose: The goals of this study are to compare EG7 - CAFs (cancer-associated fibroblasts) and MSCs (mesenchymal stem cells) transcriptome profiling (RNA-seq) generated from Next-generation Sequencing (NGS) to perform optimal high-throughput data analysis Methods: mRNA profiles of CAFs were purified from EG7 tumor bearing mice and early passage (p6) murine MSCs purchased from Cyagen were cultured in DMEM for no more than 2 passages were generated by deep sequencing, in triplicate, using Illumina HiSeq 3000. The sequence reads that passed quality filters were analyzed at the transcript isoform level TopHat followed by Cufflinks Results: Comparative high throughput RNA-sequencing (seq) analysis of purified EG7-CAFs and the early passage murine MSCs, which are thought to be precursors for some CAFs and used as the control for normal mesenchymal cells, by using an optimized data analysis workflow, we mapped about 50 million sequence reads per sample to the mouse genome (build mm10) and identified 11,839 transcripts with TopHat workflow. Approximately 1584 of the transcripts showed differential expression between the EG7 - CAFs and MSCs, with a fold change ≥ 2 and p value <0.01 Conclusions: Our results clearly support the notion that CAFs are transcriptionally different from MSCs in various pathways and biological processes associated with immune modulation, inflammation, hypoxia, and activation of oncogenic pathways
2019-11-30 | GSE141199 | GEO
Project description:The cellular diversity of stromal compartment within the tumor microenvironment might change dynamically as tumors evolve that allowing distant dissemination of tumor cells and informing the treatment options. We used single cell RNA sequencing (scRNA-seq) to provide a detailed insight of cellular components feature in bladder cancer and identify that PDGFRα+ITGA11+ CAFs were essential for lymphatic metastasis of bladder cancer. To identify molecular mechanism of PDGFRα+ITGA11+ CAFs formation, next generation sequencing (NSG) was performed to explore the upregulated genes in bladder cancer-induced PDGFRα+ITGA11+ CAFs.
2024-02-16 | GSE252645 | GEO
Project description:Transcriptomic comparison of chemosensitive and chemoresistant cells
| PRJNA131103 | ENA
Project description:The aim of our research project is to identify microRNAs involved in chemoresistance in acute myeloid leukemia patients. We performed small RNA-sequencing on baseline bone marrow samples and compared chemoresistant versus chemosensitive patient samples.
2021-02-11 | E-MTAB-8775 | biostudies-arrayexpress
Project description:Next Generation Sequencing Facilitates Quantitative Analysis of EG7-CAFs and MSCs Transcriptomes
| PRJNA592566 | ENA
Project description:Chemotherapy (CT) resistance in ovarian cancer is broad and encompasses diverse, unrelated drugs, suggesting more than one mechanism of resistance. We aimed to analyze the gene expression patterns in primary serous epithelial ovarian cancer (EOC) samples displaying different responses to first-line CT in an attempt to identify specific molecular signatures associated with response to CT. Initially, the expression profiles of 15 chemoresistant serous EOC tumors [time to recurrence (TTR) ≤6 months] and 10 chemosensitive serous EOC tumors (TTR ≥30 months) were independently analyzed which allowed the identification of specific sets of differentially expressed genes that might be functionally implicated in the evolution of the chemoresistant or the chemosensitive phenotype. Our data suggest that the intrinsic chemoresistance in serous EOC cells may be attributed to the combined action of different molecular mechanisms and factors linked with drug influx and efflux and cell proliferation, as possible implications of other molecular events including altered metabolism, apoptosis and inflammation cannot be excluded. Next, gene expression comparison using hierarchical clustering clearly distinguished chemosensitive and chemo- resistant tumors from the 25 serous EOC samples (training set), and consecutive class prediction analysis was used to develop a 43-gene classifier that was further validated in an independent cohort of 15 serous EOC patients and 2 patients with other ovarian cancer histotypes (test set). The 43-gene predictor set properly classified serous EOC patients at high risk for early (≤22 months) versus late (>22 months) relapse after initial CT. Thus, gene expression array technology can effectively classify serous EOC tumors according to CT response. The proposed 43-gene model needs further validation. 2 condition experiment: chemoresistant clinical samples versus chemosensitive samples
2011-07-23 | E-GEOD-28739 | biostudies-arrayexpress
Project description:Tumor stroma of pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant and heterogeneous cancer-associated fibroblasts (CAFs) that are critically involved in chemoresistance. However, the underlying mechanism of CAFs in chemoresistance is unclear. Here, we show that CAFR, a CAFs subset derived from oxaliplatin-resistant PDAC patients, produces more IL8 than CAFS isolated form oxaliplatin-sensitive PDAC patients. CAFR derived IL8 promotes PDAC oxaliplatin chemoresistance. Base on long non-coding RNA (lncRNA) profiling in tumor cells incubated with CAF, we identify that UPK1A-AS, which is directly induced by IL8/NF-kappa B signaling, functions as a pro-chemoresistant lncRNA and is critical for active IL8-induced oxaliplatin resistance. Impressively, blocking UPK1A-AS1 activation increases sensitivity of tumor cell response to oxaliplatin chemotherapy in vivo. Mechanically, UPK1A-AS1 strengths the interaction of Ku70 and Ku80 to enhance double-strand DNA break (DSB) repair, thereby coordinating the NHEJ pathway. Clinically, UPK1A-AS1 expression is positively correlated with IL8 expression, poor chemotherapeutic response and shorter PFS of PDAC patients. Collectively, our study discovers a lncRNA-mediated mechanism for CAF derived IL8 paracrine-dependent oxaliplatin resistance and highlights UPK1A-AS1 as potential therapeutic targets.
2021-09-16 | GSE183779 | GEO
Project description:Hepatocellular carcinoma (HCC) is a malignancy that is challenging to treat. Cancer-associated fibroblasts (CAFs) are reported to promote the malignant behavior of HCC cells via cytokines. Conophylline (CnP) has been reported to suppress activated hepatic stellate cells in liver fibrosis. We aimed to determine whether CnP is useful in suppressing tumor growth in HCC. We investigated whether CnP could suppress the HCC-promoting effect of CAFs derived from HCC tissues in vitro and in vivo. CAFs promoted the proliferation and invasion of HCC cells. CnP suppressed activated CAFs expressing α-smooth muscle actin (αSMA) and inhibited the HCC-promoting effects of CAFs. CnP significantly reduced the levels of cancer-promoting cytokines such as interleukin (IL)-6 (IL-6), IL-8, C-C Motif Chemokine Ligand 2 (CCL2), angiogenin, and osteopontin, which are secreted by CAFs. An in vivo study demonstrated that combined therapy with CnP and sorafenib against CAFs and HCC cells showed the strongest inhibition of tumor growth compared with the control and single treatment groups. Transcriptome analysis revealed that GPR68 in CAFs was strongly suppressed by CnP. The cancer-promoting effects of cytokines were eliminated by knockdown of GPR68 in CAFs. CnP inhibited the HCC-promoting effect of CAFs by suppression a number of HCC-promoting cytokines, which are secreted from CAFs expressing GPR68. Combination therapy with CnP and existing anti-cancer agents may be a promising therapeutic strategy in overcoming refractory HCC with activated CAFs.
2022-01-01 | GSE140530 | GEO