Background: Local recurrence is the major manifestation of treatment failure in patients with operable laryngeal carcinoma. Established clinicopathological factors cannot sufficiently predict patients that are likely to recur after treatment. Additional tools are therefore required to accurately identify patients at high risk for recurrence. Methods: Using Affymetrix U133A Genechips, we profiled fresh-frozen tumor tissues from 59 patients with operable laryngeal cancer. All patients were treated locally with surgery, with or without radiation therapy. We performed Cox regression proportional hazards modeling to identify multigene predictors of recurrence. The end-point of our analysis was disease-free survival (DFS). Gene models were directly validated in a separate, similarly treated cohort of 50 patients using Affymetrix chips. In an attempt to further validate our results, we profiled 12 selected genes of our model in formalin-fixed tumor tissues from an independent cohort of 75 patients, using quantitative real time-polymerase chain reaction (qRT-PCR). Results: We focused on genes univariately associated with DFS (p<0.05) in the training set. Among several gene models comprising different numbers of genes, a 30-gene model demonstrated optimal performance (log-rank, p<0.001). We directly applied these gene models to the validation set, after adjusting for non-biological experimental variability, and observed similar results. Specifically, median DFS, as predicted by the 30-gene model, was 34 and 80 months for high- and low-risk patients, respectively (p=0.01). Hazard Ratio (HR) for recurrence for the high-risk group was 3.87 (95% CI 1.28-11.73, p=0.017). Furthermore, unsupervised hierarchical clustering of the 75 patients, based on the qRT-PCR 12-gene profile, yielded two groups, which differed significantly in DFS (log-rank, p=0.027). HR= for recurrence was 2.26, (95% CI 1.08-4.76, p=0.031). Conclusion: We have established and validated gene models that can successfully stratify patients with laryngeal cancer, based on their risk for recurrence. Thus, patients with unfavorable prognosis, when accurately identified, could be ideal candidates for the application of more aggressive treatment modalities.
Identification and validation of a multigene predictor of recurrence in primary laryngeal cancer.
Age, Specimen part, Disease stage
View SamplesWe studied gene expression by RNA-seq in yeast cells in various CDK1-cyclin-depleted states.
The CDK-APC/C Oscillator Predominantly Entrains Periodic Cell-Cycle Transcription.
Disease, Cell line
View SamplesRecently, we reported the development of the C57BL/6.NOD-Aec1Aec2 mouse that carries two genetic intervals derived from the NOD mouse capable of conferring Sjgrens syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice.
Differential gene expressions in the lacrimal gland during development and onset of keratoconjunctivitis sicca in Sjögren's syndrome (SJS)-like disease of the C57BL/6.NOD-Aec1Aec2 mouse.
Sex, Age, Specimen part
View SamplesThe C57BL/6.NOD-Aec1Aec2 mouse is a model for primary Sjgrens syndrome and was constructed by introducing two genetic intervals derived from the NOD mouse that confers Sjgrens syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice.
Transcriptional landscapes of emerging autoimmunity: transient aberrations in the targeted tissue's extracellular milieu precede immune responses in Sjögren's syndrome.
Sex, Age, Specimen part
View SamplesThe transcriptome is the complete set of all RNA transcripts produced by the genome in a cell and reflects the genes that are being actively expressed. Transcriptome analysis is essential for understanding the genetic mechanism controlling the phenotype of a cell.
Characterization of transcriptomes of cochlear inner and outer hair cells.
Specimen part
View SamplesDifferential gene expression in the salivary gland during development and onset of xerostomia in Sjgrens syndrome-like disease of the C57BL/6.NOD-Aec1Aec2 mouse.
Differential gene expression in the salivary gland during development and onset of xerostomia in Sjögren's syndrome-like disease of the C57BL/6.NOD-Aec1Aec2 mouse.
Sex, Age, Specimen part
View SamplesThis study aims to investigate the role of microRNA-30c on hepatic and metabolic gene expression and physiology Overall design: For this experiment, we used male C57BL/6 mice. At an age of 8 weeks, we started them on Western diet for one month and then injected them with either PBS or increasing dose of Scr or miR-30c mimic (2.5, 5.0, and 7.5 mg/kg) for 6 weeks. Liver from these mice were harvested and flash frozen. RNA from the livers of these mice were extracted and RNA-seq was performed.
MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice.
No sample metadata fields
View SamplesDespite an abundance of evidence to the contrary from animal studies, large clinical trials on humans have shown that estrogen administered to post-menopausal women increases the risk of cardiovascular disease. However, timing may be everything, as estrogen is often administered immediately after ovariectomy (ovx) in animal studies, while estrogen administration in human studies occurred many years post-menopause. This study investigates the discrepancy by administering 17-estradiol (E2) in a slow-release capsule to Norway Brown rats both immediately following ovx and 9 weeks post-ovx (Late), and studying differences in gene expression between these 2 groups as compared to age-matched ovx and sham operated animals. Two different types of microarray were used to analyze the left ventricles from these groups: an Affymetrix array (2 samples/group, each sample contained total RNAs pooled from 3 rats) and an Inflammatory Cytokines and Receptors PCR array (N=4 /group). Key genes were analyzed by western blotting. Ovx without replacement led to an increase in caspase 3, caspase 9, calpain 2, MMP9, and TNF. Caspase 6, STAT3, and CD11b increased in the Late group, while TIMP2, MMP14, and collagen I 1 were decreased. MADD and fibronectin were increased in both Ovx and Late. TNF protein levels increased with Late replacement. Many of these changes were prevented by early E2 replacement. These findings suggest that increased TNF may be involved in some of the deleterious effects of delayed E2 administration seen in human studies.
Impact of aging vs. estrogen loss on cardiac gene expression: estrogen replacement and inflammation.
Sex, Specimen part, Treatment
View SamplesThe highly characterized Sox9-EGFP transgenic mouse model, which permits the isolation and analysis of four distinct IEC populations using fluorescence-activated cell sorting (FACS) based on differing levels of cellular EGFP intensity. These are Sox9-EGFP Low (actively cycling IESCs), Sox9-EGFP Sublow (progenitor cells), Sox9-EGFP Neg (mostly differentiated enterocytes as well as goblet cells and Paneth cells), and Sox9-EGFP High (primarily EECs). We evaluated mRNA expression profiles by next-generation high-throughput RNA-sequencing in FACS purified Sox9-Low cells from germ-free (GF) and conventionalized (CV) mice. Overall design: To assess the effect of microbiota on the intestinal epithelial stem cells population, we used four pairs of female GF Sox9-EGFP littermates. One littermate from each pair was randomly selected at 8-10 weeks of age for conventionalization. Following a two-week conventionalization, the jejunal epithelial tissue from both the CV and GF littermates were harvested and IECs were sorted by FACS. RNA was isolated from the four sorted populations from each animal, as well as from non-sorted (NS) IECs, and subject to small RNA sequencing. Additionally, Sox9-Low samples were profiled for mRNAs using mRNA-seq. Reads were aligned to the mouse genome and quantified using Salmon followed by edgeR. To avoid noise introduced by lowly expressed transcripts, we analyzed only robustly expressed transcripts defined as those with an expression of at least 10 counts per million (CPM).
Functional Transcriptomics in Diverse Intestinal Epithelial Cell Types Reveals Robust MicroRNA Sensitivity in Intestinal Stem Cells to Microbial Status.
Sex, Specimen part, Cell line, Subject
View SamplesThis study compared the expression signatures of HL60 cells +/- tretinoin. This data was then used for another study showing a method for high-throughput gene expression signature analysis.
A method for high-throughput gene expression signature analysis.
No sample metadata fields
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