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FGFR1 expression defines clinically distinct subtypes in pancreatic cancer.

ABSTRACT: BACKGROUND:The clinical significance of fibroblast growth factor receptor 1 (FGFR1) protein expression in pancreatic cancer is largely unknown. In this study, we aimed investigate the clinical significance of FGFR1 expression in pancreatic cancer. METHODS:First, we investigated the relationship between FGFR pathway gene expression and clinicopathological data in three pancreatic cancer cohorts containing 313 cases. Subsequently, to confirm the findings from the discovery cohorts, we performed immunohistochemistry (IHC) of FGFR1 protein in a validation cohort of 205 pancreatic cancer cases. RESULTS:In discovery cohort 1, FGFR1 and Klotho beta (KLB) overexpression was associated with low tumor stage (P?

SUBMITTER: Haq F

PROVIDER: S-EPMC6311038 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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FGFR1 expression defines clinically distinct subtypes in pancreatic cancer.

Haq Farhan F Sung You-Na YN Park Inkeun I Kayani Mahmood Akhtar MA Yousuf Faizah F Hong Seung-Mo SM Ahn Sung-Min SM

Journal of translational medicine 20181228 1

<h4>Background</h4>The clinical significance of fibroblast growth factor receptor 1 (FGFR1) protein expression in pancreatic cancer is largely unknown. In this study, we aimed investigate the clinical significance of FGFR1 expression in pancreatic cancer.<h4>Methods</h4>First, we investigated the relationship between FGFR pathway gene expression and clinicopathological data in three pancreatic cancer cohorts containing 313 cases. Subsequently, to confirm the findings from the discovery cohorts, ...[more]

PMID: 30593273

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Project description:BackgroundGene expression profiling has been used to define molecular phenotypes of complex diseases such as breast cancer. The luminal A and basal-like subtypes have been repeatedly identified and validated as the two main subtypes out of a total of five molecular subtypes of breast cancer. These two are associated with distinctly different gene expression patterns and more importantly, a significant difference in clinical outcome. To further validate and more thoroughly characterize these two subtypes at the molecular level in tumors at an early stage, we report a gene expression profiling study using three different DNA microarray platforms.ResultsExpression data from 20 tumor biopsies of early stage breast carcinomas were generated on three different DNA microarray platforms; Applied Biosystems Human Genome Survey Microarrays, Stanford cDNA Microarrays and Agilent's Whole Human Genome Oligo Microarrays, and the resulting gene expression patterns were analyzed. Both unsupervised and supervised analyses identified the different clinically relevant subtypes of breast tumours, and the results were consistent across all three platforms. Gene classification and biological pathway analyses of the genes differentially expressed between the two main subtypes revealed different molecular mechanisms descriptive of the two expression-based subtypes: Signature genes of the luminal A subtype were over-represented by genes involved in fatty acid metabolism and steroid hormone-mediated signaling pathways, in particular estrogen receptor signaling, while signature genes of the basal-like subtype were over-represented by genes involved in cell proliferation and differentiation, p21-mediated pathway, and G1-S checkpoint of cell cycle-signaling pathways. A minimal set of 54 genes that best discriminated the two subtypes was identified using the combined data sets generated from the three different array platforms. These predictor genes were further verified by TaqMan Gene Expression assays.ConclusionWe have identified and validated the two main previously defined clinically relevant subtypes, luminal A and basal-like, in a small set of early stage breast carcinomas. Signature genes characterizing these two subtypes revealed that distinct molecular mechanisms might have been pre-programmed at an early stage in different subtypes of the disease. Our results provide further evidence that these breast tumor subtypes represent biologically distinct disease entities and may require different therapeutic strategies. Finally, validated by multiple gene expression platforms, including quantitative PCR, the set of 54 predictor genes identified in this study may define potential prognostic molecular markers for breast cancer.

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FGFR1 expression defines clinically distinct subtypes in pancreatic cancer.

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FGFR1 expression defines clinically distinct subtypes in pancreatic cancer.

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