Transcription profiling by array of head and neck squamous cell carcinoma samples with focus on extracellular matrix components in margin of surgical resecate
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Michal Kolar
PROVIDER: E-MTAB-5852 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Tumor stroma strongly influences behaviour of cancer cells. Here, we study influence of the tumor stroma on transcription activity of head and neck squamous cell carcinoma cells. In particular, we compare transcription activity of the cancer cells in relation to expression of a putative prognostic marker tenascin in the tumor stroma.
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Project description:We studied overall difference in gene expression between head and neck squamous cell carcinoma tumours and normal mucosa. Samples were collected from patients during surgery and almost in all cases, paired samples were collected: tumour tissue and normal mucosa from the opposite side. Tumour samples were TNM staged by pathologist and tested for human papillomavirus infection (HPV) high-risk types 16 and 18 by PCR of E6 and E7 mRNA. If possible, patients were followed up and their disease-free and overall survival is available (up to 11 years after surgery).
2020-12-31 | E-MTAB-8588 | biostudies-arrayexpress
Project description:In this study, we set the presence of smooth muscle actin (SMA)-positive cancer-associated fibroblasts (CAFs) in relation to galectin-1 and its in vivo competitor (galectin-3). In squamous cell carcinomas of head and neck, upregulation of galectin-1 presence is highly significantly correlated to presence of smooth muscle actin-positive cancer-associated fibroblasts in the tumor. In order to pinpoint correlations on the molecular level, we applied microarray analyses to the transcription profiles of the corresponding tumors. Significant correlations of several transcripts were detected with the protein level of galectin-1 in the cancer-associated fibroblasts.
2012-11-01 | E-MTAB-850 | biostudies-arrayexpress
Project description:We model processes of wound healing and tumor growth, by studying the effects of normal and cancer epithelial cells on normal fibroblasts and their reciprocal effect on normal keratinocytes in vitro. We find strong parallels between the two processes and compare our observations with transcriptional analysis of 24 clinical samples of squamous cell carcinoma. This dataset contains the clinical samples, for tissue culture samples, see E-MTAB-1064. Clinical samples of carcinoma tissues were compared to paired normal mucosae.
2013-11-02 | E-MTAB-1065 | biostudies-arrayexpress
Project description:Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary cancer in the liver. ICC is an aggressive cancer with poor prognosis and limited therapeutic strategies. The identification of new drug targets and prognostic biomarkers is an important clinical challenge for ICC. The presence of an abundant stroma is a histological hallmark of ICC. Given the well established role of the stromal compartment in the progression of cancer diseases, we hypothesized that relevant biomarkers could be identified by analyzing the stroma of ICC. By combining laser capture microdissection and gene expression profiling we demonstrated that ICC stromal cells exhibit dramatic genomic changes. We identified a signature of 1,073 non-redundant genes that significantly discriminate the tumor stroma from non tumor fibrous tissue. Functional analysis of differentially expressed genes demonstrated that up-regulated genes in the stroma of ICC were related to cell cycle, extracellular matrix and Transforming Growth Factor beta (TGFM-NM-2) pathways. Tissue microarray analysis using an independent cohort of 40 ICC patients validated at a protein level the increase expression of Collagen 4, Laminin, Osteopontin/SPP1, KIAA0101 and TGFM-NM-22 genes in the stroma of ICC. Statistical analysis of clinical and pathological features demonstrated that the expression of Osteopontin, TGFM-NM-22 and Laminin in the stroma of ICC was significantly correlated with patient overall survival. More importantly, multivariate analysis demonstrated that the stromal expression of Osteopontin was an independent prognostic marker for overall and disease-free survival. Conclusion: The study identifies clinically relevant genomic alterations in the stroma of ICC, including candidates biomarkers for prognosis, supporting the idea that tumor stroma is an important factor for ICC onset and progression. 20 RNA samples were analyzed, from 10 patients with ICC. For each patient, RNA were isolated from laser capture microdissected (LCM) stroma from tumor and non tumor areas.
2013-06-21 | E-GEOD-45001 | biostudies-arrayexpress
Project description:Ovarian cancer is the most lethal malignancy in the United States. In the year 2012, there will be an estimated 22,280 new cases and 15,500 deaths from ovarian cancer in the country (Siegel et al., 2012). While studies on ovarian cancer pathogenesis were mainly focused on the epithelial component of the tumor, understanding in the role of cancer associated fibroblasts (CAFs) in ovarian cancer progression is limited. We hypothesized that comparing the gene expression profiles of different components from laser capture microdissected ovarian tissue will allow us to identify an ovarian CAFs specific gene signature which accounts for the supportive role of CAFs in ovarian cancer progression. In this study, gene expression profiling was completed for 31 cancer stroma samples and 32 samples of epithelial component from high grade serous ovarian cancer patients. 8 microdissected normal ovarian stroma and 6 normal human ovarian surface epithelium (HOSE) samples were also included in the study. By comparing the expression data from cancer stroma against that from normal stroma, cancer cells and HOSE, we identified a set of differential expressed genes in ovarian CAFs which showed correlation with cancer patient survival. Further study on these genes can reveal their roles in ovarian cancer progression and pathogenesis. Ultimately, ovarian CAFs specified genes identified in this study may aid in the classification and enhancement of patient outcome. Transcriptome profiling analyses were performed on 31 laser microdissected cancer associated stroma samples, 32 epithelial tumor samples from high grade serous ovarian cancer patients, 8 microdissected normal ovarian stroma samples and 6 ovarian surface epthelium (HOSE) samples using the Affymetrix human genome U133 Plus 2.0 microarray.
2014-09-11 | E-GEOD-40595 | biostudies-arrayexpress
Project description:The ventromedial nucleus of the hypothalamus (VMH) is thought to a satiety center and a potential target for anti-obesity therapy. Electroconvulsive seizure (ECS) therapy is highly effective in psychiatric diseases including depression, but also implicated beneficial effects on other neurological diseases. Although it has been reported that the neurons in the VMH are strongly activated by ECS stimulation, the effect of ECS in this hypothalamic subnucleus remains unknown. To address this issue, we investigated molecular changes in the VMH in response to ECS by utilizing a method of laser-capture microdissection coupled with microarray analysis, and examined behavioral effects of ECS via VMH activation. ECS significantly induced gene expression not only immediate-early genes such as Fos, Fosb and Jun, but also Bdnf, Adcyap1, and Hrh1 in the VMH after a single or repeated stimulus. Mice received one or 7 times shock of ECS and their brains were collected at 2 h (VMH_1stECS2h, VMH_7thECS2h) or 6 h after shock (VMH_1stECS6h, VMH_7thECS6h). The brains of sham-treated animals were collected at 2 h after treatment(VMH_sham). The VMH was microdissected from dehydrated brain sections, and its total RNA was extracted. RNA samples from two or three animals were pooled to minimize the impact of biological variance. After nucleotide amplification by the ovation amplification, the gene expression profiles were obtained by the Affymetrix microarray analysis. The microarray analysis was performed twice using different sets of animals.
2012-05-29 | E-GEOD-38311 | biostudies-arrayexpress
Project description:Rationale Electroconvulsive seizure (ECS) therapy is a nonchemical treatment for depression. Since ECS up-regulates expression of c-Fos in the paraventricular nucleus of hypothalamus (PVN), the function of which is frequently influenced in depression, we hypothesized that ECS modulates functions of the PVN and contributes to its antidepressant effects. Objectives To identify gene expression changes in the mouse PVN by ECS treatment Material and methods First, we established a method to amplify nucleotides from small quantities of RNA. Mice received one shock of ECS and their brains were collected at 2 or 6 h after shock. The PVN was microdissected from dehydrated brain sections, its total RNA was extracted and microarray analysis was applied. Results At 2 h after ECS, 2.6% (589 genes) of the probes showed more than 2-fold decrease, and 0.9% (205 genes) showed more than 2-fold increase. To confirm the expression changes, genes showing differential expression with a wide range in the microarray were analyzed by qPCR. Among the genes with more than 2-fold change by ECS, down-regulated 94 genes and up-regulated 24 genes have been reported the association with anxiety, bipolar disorder or mood disorder by the Ingenuity knowledge database. The groups of down-regulated genes, which are suggested to modulate the function of the PVN or associate to psychiatric disorders, include neuropeptides (Cck), kinases (Prkcb, Prkcc, Camk2a), transcription factors (Bcl6, Tbr1), transporters (Aqp4) and others (Fmr1). Conclusion The present results indicate that ECS treatment can modulate the functions of PVN via a series of gene expression changes, and may contribute to its antidepressant effects at least in part. Mice received one shock of ECS and their brains were collected at 2 h (PVN_ECS2h_1, PVN_ECS2h_2) or 6 h after shock (PVN_ECS6h_1, PVN_ECS6h_2). The brains of sham-treated animals were collected at 2 h after treatment (PVN_sham_1, PVN_sham_2). The PVN was microdissected from dehydrated brain sections, and its total RNA was extracted. RNA samples from two or three animals were pooled to minimize the impact of biological variance. After nucleotide amplification by the ovation amplification, the gene expression profiles were obtained by the Affymetrix microarray analysis. The microarray analysis was performed twice using different sets of animals.
2012-01-24 | E-GEOD-35259 | biostudies-arrayexpress
Project description:Specific deletion of Tgfbr2 in FSP1+ fibroblasts (Tgfbr2fspKO) induced development of SCC in forestomach with 100% penetrance. Tgfbr2fspKO mice die by 7 weeks with a median survival of 38 days (Log rank p<0.001). Examination of Tgfbr2fspKO forestomach between embryonic day 16 (E16) and 5 weeks of age suggested that hyperplasia began during week 3 and was followed by dysplasia, carcinoma in situ, and invasive squamous cell carcinoma (SCC). The aim of this study was to elucidate genetic aberrations in the tumor associated stroma and SCC tumor using array comparative genomic hybridization (CGH) analysis. Laser capture micro-dissection was performed using formalin-fixed, paraffin-embedded, 5 week old Tgfbr2fspKO forestomach tissues. Genetic loss of cyclin-dependent kinase inhibitor, Cdkn2a/ p16Ink4A was found in laser captured epithelia of all three Tgfbr2fspKO forestomachs. Surprisingly, no genetic change was seen in the tumor associated stroma. Examination of human esophageal SCC showed a down-regulation of TGFβ receptor 2 (TβRII) in the stromal fibroblasts as well as increased inflammation and DNA damage. Published literature showed that loss of Cdkn2a/p16Ink4A tumor suppressor is the common event in human ESCCs. Our study suggests anti-inflammation may be a new therapeutic option in treating human SCCs with down-regulation of TβRII in the stroma. Laser capture microdissection of Tgfbr2flox/flox (n=3) and Tgfbr2fspKO (n=3) forestomach tissues was performed using an Arcturus XT (Life Technologies, CA, USA). Mouse background strain is C57Bl6. Frozen tissue sections on PEN membrane frame slides (Applied Biosystems) were H&E stained followed by dehydration using the standard protocol to improve visualization of the cells at the microscope. The epithelia and stroma were identified by morphology, captured using a low-power infrared laser pulse, and transferred onto a cap (Capsure™ Macro LCM Caps, Life Technologies). The DNA was extracted using a QIAamp DNA micro kit (Qiagen, CA, USA). Array-CGH was performed using test DNA from laser captured epithelia and stroma from Tgfbr2fspKO mice. Reference DNA was laser captured from the epithelia of normal forestomach of Tgfbr2flox/flox mice. DNA was labeled with Cy3 (test) or Cy5 (control) fluorescent dyes (Perkin Elmer, MA, USA) according to the BioPrime array CGH genomic labeling protocol (Invitrogen, Carlsbad, CA) and cleaned using Microcon YM-30 filters (Millipore, Billerica, MA). Hybridization was carried out using Mouse Genome CGH Microarray 4x180 K format from Agilent Technologies (Santa Clara, CA) according to CGH Procedures for Genomic DNA Analysis (Agilent Technologies). Slides were hybridized for 20 hours, washed, and scanned with an Agilent microarray scanner. Data was analyzed using Feature Extraction® and CGH Analytics® software packages (Agilent Technologies).
2012-12-06 | E-GEOD-42773 | biostudies-arrayexpress
Project description:Analysis of a clinical urothelial cancer cohort for their spatial tryptic peptide composition in two different tissue types, tumor and stroma, and two tumor subtypes, muscle-infiltrating and non muscle-infiltrating tumors.
2021-06-04 | PXD026459 | Pride