Microenvironmental regulation by miRNAs in pancreatic cancer.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens
PROVIDER: GSE71533 | GEO | 2017/07/29
SECONDARY ACCESSION(S): PRJNA291451
REPOSITORIES: GEO
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Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by a KRAS-driven inflammatory program and a desmoplastic stroma, which contribute to the profoundly chemoresistant phenotype. The tumor stroma contains an abundance of cancer-associated fibroblasts (CAFs), which engage in extensive paracrine crosstalk with tumor cells to perpetuate pro-tumorigenic inflammation. Interleukin-1α (IL1α), a pleiotropic, tumor cell-derived cytokine, plays a critical role in shaping the stromal landscape. We have identified p38 MAPK as a key regulator of IL1α gene expression and utilized single-cell RNA sequencing to study the role of p38 MAPK in PDAC
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Project description:In this work, we reported a strategy to produce 3D in vitro microtissues of pancreatic ductal adenocarcinoma (PDAC) for studying the desmoplastic reaction activated by the stroma-cancer crosstalk. The purpose of this dataset was to examine the transcriptional expression changes of normal fibroblasts (NF), cancer-associated fibroblasts (CAF) and pancreatic adenocarcinoma cell line (PT45) in 3D versus 2D culture and in mono-culture versus co-culture. Illumina Human BeadChips were used to profile the transcriptome after 12 days of culture. We reported that human PDAC microtissues, obtained by co-culturing PT45 with NF or CAF within biodegradable microcarriers in spinner flask bioreactor, closely recapitulate key PDAC microenvironment characteristics.
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Project description:Background: Only a subset of radically-resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from chemotherapy, and identification of novel prognostic factors is warranted. Recently miRNAs emerged as diagnostic biomarkers and innovative therapeutic targets, while high-throughput arrays are opening new opportunities to evaluate whether they can also predict clinical outcome. The present study evaluated whether comprehensive miRNA expression profiling correlated with overall survival (OS) in resected PDAC patients. Methodology/Principal Findings: High-resolution miRNA profiles were obtained with the Toray’s 3D-GeneTM miRNA chip, detecting more than 1200 types of human miRNA. RNA was isolated from paraffin-embedded primary tumors of 26 radically resected stage-pT3N1 homogeneously treated patients (adjuvant gemcitabine 1000mg/m2/day, days-1/8/15, every 28days), carefully selected according to their outcome (OS<12 vs. OS>30 months, i.e. short/long-OS). Highly stringent statistics included t-test, distance matrix with Spearman-ranked correlation, and iterative approaches. Unsupervised hierarchical analysis revealed that PDAC specimens clustered according to their short/long-OS classification, while the feature selection algorithm RELIEF identified the top-4 discriminating miRNAs between the two groups. These miRNAs target more than 1500 transcripts, including 169 targeted by two or more of these miRNAs. MiR-211 emerged as the best discriminating miRNA, with significantly higher expression in long- vs. short-OS patients. The expression of this miRNA was subsequently assessed by quantitative-PCR in an independent cohort of laser microdissected tumors from 60 resected stage-pT3N1 PDAC patients treated with the same gemcitabine regimen. Patients with low miR-211 expression according to median value had a significantly shorter median OS (14.8, 95%CI=13.1-16.5, vs. 25.7 months, 95%CI=16.2-35.1, log-rank P=0.004). Multivariate analysis demonstrated that low miR-211 expression was an independent factor of poor prognosis (hazard ratio 2.3, P=0.03) after adjusting for all the factors influencing outcome. 19 samples, duplicated gene spots
2012-11-22 | E-GEOD-38781 | biostudies-arrayexpress