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Platform
GSE74777
Homo sapiens
106 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
One hundred and seven lung Squamous Cell Carcinomas collected from early stage (stage I+II; AJCC 7th edition) patients at the National Cancer Center Hospital (Tokyo, Japan) between 1997 and 2008 were hybridized to the Human Transcriptome (HT) Array 2.0
Publication Title
A Two-Gene Prognostic Classifier for Early-Stage Lung Squamous Cell Carcinoma in Multiple Large-Scale and Geographically Diverse Cohorts.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 107 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Tobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure. We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p<0.001 and fold-change>1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001) and TTK (p=0.002) expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers. Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers.
Publication Title
Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Many preclinical therapy studies have focused on a small number of well-described mouse allograft or human xenograft models that poorly represent the heterogeneity of human disease. Here we have assembled a panel of mouse mammary cell lines that metastasize in syngeneic mouse hosts and we have assessed gene expression programs in the untreated primary tumors with the goal of generating information that may be useful to the identification of biomarkers that predict response to therapeutic intervention.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The expression array data will be merged with Rel-B ChIP-Seq data in HL cell lines. This will show REL-B direct and indirect controlled downstream target genes
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The human hair follicle bulge is an important niche for keratinocyte stem cells (KSC). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSC. In this study, we determined the distribution of label-retaining cells to carefully define the human anagen bulge. Using navigated-laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and Activin/BMP signaling were over-represented in the bulge while genes responsible for cell proliferation were under-represented, consistent with quiescent non-cycling KSC in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1 while CD24, 34, 71 and 146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hi24lo34lo71lo146lo) obtained from hair follicle suspensions demonstrated high colony forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells.
Publication Title
Characterization and isolation of stem cell-enriched human hair follicle bulge cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Tamoxifen (TAM), used for adjuvant therapy of breast cancer, also increases the risk of endometrial cancer. To compare TAM-induced transcriptional changes we examined human and monkey uterus, as well as cultured normal human mammary epithelial cells (NHMECs) and human endometrial stromal cells (HESCs). Uterine DNA from TAM-exposed women (n=15) and monkeys (Erythrocebus patas n=5, and Macaca fascicularis n=12) showed no difference in 5-methyl-cytosine (5-meC) levels compared to unexposed controls. Studies comparing NHMECs and HESCs exposed to 10 M TAM for 48 hr showed cell-specific differences by microarray, with confirmation by RT-PCR. In TAM-exposed NHMECs there was significant up-regulation of interferon signaling and immune response pathways, while the TAM-exposed HESCs showed significant up-regulation of steroid and fatty acid biosynthesis pathways. Promoter region CpG islands of several genes highly up-regulated by TAM in each cell type (NHMECs: MX1 and STAT1; HESCs: PPARG, SREBF2, HMCGS and Prune2), were examined for 5-meC, but the levels ( 7%), were too low to measure accurately. We also examined several histone H3 lysine dimethylases by Western blot, and showed a significant depletion of total H3 histone, H3K4, H3K27 and H3K36 in TAM-exposed HESCs, with similar but non-significant changes in TAM-exposed NHMECs. Whereas TAM exposure had no discernible effect on 5-meC levels in primate uterus, TAM exposure induced up-regulation of different transcriptional pathways in NHMECs and HESCs, and concomitantly depleted H3 histone lysine dimethylase levels. Therefore, transcriptional dysregulation by TAM, including reduction of histone H3 dimethylase levels, may be related to TAM-induced endometrial carcinogenesis.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Tamoxifen (TAM), used for adjuvant therapy of breast cancer, also increases the risk of endometrial cancer. To compare TAM-induced transcriptional changes we examined human and monkey uterus, as well as cultured normal human mammary epithelial cells (NHMECs) and human endometrial stromal cells (HESCs). Uterine DNA from TAM-exposed women (n=15) and monkeys (Erythrocebus patas n=5, and Macaca fascicularis n=12) showed no difference in 5-methyl-cytosine (5-meC) levels compared to unexposed controls. Studies comparing NHMECs and HESCs exposed to 10 M TAM for 48 hr showed cell-specific differences by microarray, with confirmation by RT-PCR. In TAM-exposed NHMECs there was significant up-regulation of interferon signaling and immune response pathways, while the TAM-exposed HESCs showed significant up-regulation of steroid and fatty acid biosynthesis pathways. Promoter region CpG islands of several genes highly up-regulated by TAM in each cell type (NHMECs: MX1 and STAT1; HESCs: PPARG, SREBF2, HMCGS and Prune2), were examined for 5-meC, but the levels ( 7%), were too low to measure accurately. We also examined several histone H3 lysine dimethylases by Western blot, and showed a significant depletion of total H3 histone, H3K4, H3K27 and H3K36 in TAM-exposed HESCs, with similar but non-significant changes in TAM-exposed NHMECs. Whereas TAM exposure had no discernible effect on 5-meC levels in primate uterus, TAM exposure induced up-regulation of different transcriptional pathways in NHMECs and HESCs, and concomitantly depleted H3 histone lysine dimethylase levels. Therefore, transcriptional dysregulation by TAM, including reduction of histone H3 dimethylase levels, may be related to TAM-induced endometrial carcinogenesis.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Expression profiling of mouse ing2 -/- testis vs WT reveals gene expression differences consistent with spermatogenic arrest and infertility. Ing2 is indispensable for male germ cell development in mice. While mice deficient for Ing2 were born and grew without apparent abnormalities, male, but not female, were infertile, consistent with the highest expression of Ing2 in testes in wild-type mice and in humans. Histological and DNA content analyses in Ing2-/- testes revealed a spermatogenesis arrest at meiotic phase and enhanced apoptosis associated with increased p53, resulting in a decline in mature spermatozoa, which became more severe in older age. HDAC1 accumulation and core histone deacetylation at pachytene stage were impaired in Ing2-/- testes, suggesting that the recruitment of HDAC1 by Ing2 plays a critical role in spermatogenesis. This study establishes Ing2 as a novel mammalian regulator of spermatocyte differentiation, which coordinates spermatogenesis stage-specific histone modifications. This study has implications in understanding human male infertility.
Publication Title
Targeted disruption of Ing2 results in defective spermatogenesis and development of soft-tissue sarcomas.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of RNAs extracted from early passage and late passage (immortalized) mouse embryonic fibroblasts (MEFs)
Publication Title
A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20.
Sample Metadata Fields
Specimen part
View Samples