MicroRNA Signaling Pathway Network in Pancreatic Ductal Adenocarcinoma

Sun, Longhao; Chua, Corrine Ying Xuan; Zhang, Zhixiang; Chiao, Paul J.; Zhang, Wei

doi:10.1016/j.jgg.2015.07.003

Cited by 18 publications

(16 citation statements)

References 130 publications

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“…Many of the miRs that were differentially abundant across the clusters (Figure 5B, Table S6, Figure S4C) have been reported as prognostic, as differentially abundant between non-neoplastic and neoplastic tissue, or as functionally involved in signalling pathways in pancreatic cancer (Frampton et al, 2015; Halkova et al, 2015; Hernandez and Lucas, 2016; Lee et al, 2015; Lou et al, 2013; Sun et al, 2015). For example, miR-21 has been reported to be prognostic in pancreatic cancer (Frampton et al, 2015), and to be more abundant in tumors than in non-neoplastic pancreatic tissue (Halkova et al, 2015; Hernandez and Lucas, 2016).…”

Section: Resultsmentioning

confidence: 99%

Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

Raphael¹,

Hruban²,

Aguirre³

et al. 2017

Cancer Cell

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1,072

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SUMMARY We performed integrated genomic, transcriptomic and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1 and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1 and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.

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Section: Resultsmentioning

confidence: 99%

Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

Raphael¹,

Hruban²,

Aguirre³

et al. 2017

Cancer Cell

Self Cite

1,480

1,072

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“…This panel was designed and validated with the intent to be incorporated into the routine clinical testing. Table 1 not only summarizes the role and biological function of each miRNA present in this panel but also describes their clinical relevance [16,33,34,42,43]. miRNA is obtained using the miRNeasy FFPE Kit (Qiagen, Hilden, Germany), and it requires four to six FFPE (formalin-fixed, paraffin-embedded) unstained slides of 5 μm each.…”

Section: Mirna and Pancreatic Diseases: The Dartmouth-hitchcock Medicmentioning

confidence: 99%

miRNA analysis in pancreatic cancer: the Dartmouth experience

Abreu

Tsongalis

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Pancreatic cancer is considered one of the most lethal cancers being the fourth leading cause of cancer deaths in adults in the United States because of the lack of early signs and symptoms and the lack of early detection. Pancreatic ductal adenocarcinoma (PDAC) is the most common histological type among pancreatic cancers, representing 80%-90% of all solid tumors of the pancreas. The majority of PDAC develops from three precursor lesions: pancreatic intraepithelial neoplasia, intraductual papillary mucinous neoplasm and mucinous cystic neoplasm.

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“…In addition, miRNAs are involved in tumorigenesis and progression of malignancies via different mechanisms, including control of cell cycle [21, 22], apoptosis [23, 24], autophagy [25], epithelial-mesenchymal transition [26], drug resistance [27] and metabolic reprogramming [28]. All of the above data indicate that miRNAs have the potential to be novel diagnostic and prognostic biomarkers for malignant tumors.…”

Section: Discussionmentioning

confidence: 99%

Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive Tract

Zhang

Huang

Chen

2017

Cell Physiol Biochem

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Background/Aims: MicroRNAs participate in various biological processes in malignant tumors. However, the mechanisms of miR-224-5p in digestive system cancers are not fully understood. A comprehensive investigation of the clinical value and potential targets of miR-224-5p in cancers of the digestive tract is necessary. Methods: Expression profiling data and related-prognostic data of miR-224-5p were acquired from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress, and published literature. The potential target mRNAs of miR-224-5p were predicted using bioinformatics methods and finally annotated using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: MiR-224-5p is up-regulated in digestive system cancers (SMD=0.69, 95% CI: 0.43-0.96, P<0.0001) and exhibits a moderate diagnostic ability (AUC=0.84, 95% CI: 0.80-0.87). Our data also demonstrated that miR-224-5p is statistically significantly correlated with overall survival univariate analysis (HR=1.69, 95% CI: 1.15-2.49, P=0.007) and multivariate analysis (HR=2.39, 95% CI: 1.74-3.30, P<0.0001). In total, 388 potential miR-224-5p target mRNAs were predicted by bioinformatics methods. GO annotation analysis revealed that the top terms of miR-224-5p in biological process, cellular component and molecular function were system development, neuron part, and transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding, respectively. Moreover, eight pathways were identified in KEGG pathway enrichment analysis. Conclusions: MiR-224-5p is up-regulated and has the potential to become a diagnostic and prognostic biomarker in digestive system cancers. MiR-224-5p might play vital roles in cancers of the digestive tract but the exact molecular mechanisms need further study and verification.

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MicroRNA Signaling Pathway Network in Pancreatic Ductal Adenocarcinoma

Cited by 18 publications

References 130 publications

Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

miRNA analysis in pancreatic cancer: the Dartmouth experience

Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive Tract

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