Adrenocortical Carcinoma Gene Expression Profiling
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PROVIDER: PRJNA121859 | ENA |
REPOSITORIES: ENA
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Project description:microRNa expression profiling in adrenal myelolipoma, adrenocortical carcinoma and adrenocortical adenoma
| PRJNA449060 | ENA
Project description:Background: Adrenocortical carcinoma (ACC) is associated with poor survival rates. The objective of the study was to analyze ACC gene expression profiling data prognostic biomarkers and novel therapeutic targets. Methods: 44 ACC and 4 normal adrenal glands were profiled on Affymetrix U133 Plus 2 expression microarrays and pathway and transcriptional enrichment analysis performed. Protein levels were determined by western blot. Drug efficacy was assessed against ACC cell lines. Previously published expression datasets were analyzed as validation data sets. Results: Pathway enrichment analysis identified marked dysregulation of cyclin-dependent kinases and mitosis. Over-expression of PTTG1, which encodes securin, a negative regulator of p53, was identified as a marker of poor survival. Median survival for patients with tumors expressing high PTTG1 levels (log2 ratio of PTTG1 to average beta-actin <-3.04 ) was 1.8 years compared to 9.0 years if tumors expressed lower levels of PTTG1 (P<0.0001). These findings were confirmed by our analysis of previously published datasets. Treatment of ACC cell lines with vorinostat decreased securin levels and inhibited cell growth (IC50s of 1.69 uM and 0.891 uM, for SW-13 and H295R, respectively). Conclusion: Over-expression of PTTG1 is correlated with poor survival in ACC. PTTG1/securin is a prognostic biomarker and warrants investigation as a therapeutic target.
2013-11-21 | GSE19750 | GEO
Project description:Adrenocortical carcinoma is a rare tumour with a poor prognosis. The currently available medical treatment options of adrenocortical cancer are limited. In the present study we examine the potential antitumoral effects of 9-cis-retinoic acid (9-cisRA) on the adrenocortical cancer cell line NCI-H295R.
2013-02-10 | GSE43090 | GEO
Project description:Adrenocortical carcinoma (ACC) is an aggressive endocrine tumor with a poor 5 year survival rate of 10-20%. We used expression profiling to assess the transcriptional changes associated with ACC as compared to normal adrenal glands with the goal of identifying new targets for treatment. Fourteen ACC tumors were profiled on both Affymetrix U133 Plus 2 or Agilent 22K Human Genome arrays; an additional six tumors were profiled on one or the other array. The data demonstrate a marked dysregulation of the cell cycle control, focused on sister chromatid adhesion and cytokinesis in the G2/M transistion. Genes associated with this pattern, and identified because of coordinate expression with CDC2, were capable of clustering ACC into two clusters that almost completely recapitulated histological grade. Exploration of the data sets by both Gene Set Enrichment Analysis and GeneGo Interactome analysis identified additional dysregulation of the IGF2-IGF1R axis, aside from IGF2 over-expression, as an early event present in low grade tumors. Additionally, p53 and MDM2 were consistently identified as drivers in leading edge analyses of the tumors, implicating the p53 pathway in ACC pathogenesis. Finally, over-expression of PTTG1, which encodes securin, and is involved in sister chromatid adhesion as well as negative regulation of p53, was associated with poor prognosis in our samples. Taken together, these data point toward a tumor type driven in part by dysregulated IGF2 signaling in the context of a lack of a functional p53 response, with potential vulnerabilities in the G2/M transition that may make viable therapeutic targets.
2013-11-21 | GSE19775 | GEO
Project description:Background: Adrenal myelolipoma (AML) is a relatively common and invariably benign tumor composed of adipose tissue and hematopoietic elements. Due to the variable proportion of fat and hematopoietic elements, it is sometimes challenging to differentiate AML from adrenocortical carcinoma (ACC). MicroRNAs have been identified as promising biomarkers in many tumors, including adrenocortical neoplasms, but the microRNA expression of adrenal myelolipoma has not been investigated, yet. Aims: To perform a large scale microRNA expression profiling in adrenal myelolipoma, benign and malignant adrenocortical tumors to identify potential microRNA biomarkers. Methods: Next-generation sequencing (NGS) on 30 formalin-fixed paraffin-embedded archived tissue samples (discovery cohort: 10 adrenocortical adenoma (ACA), 10 ACC and 10 myelolipoma) was performed by Illumina MiSeq. Significantly differentially expressed microRNAs were validated by real-time RT-qPCR in an independent validation cohort comprised of 10 ACA, 10 myelolipoma and 9 ACC samples. Results: We have found relative overexpression of miR- 451a, miR-486-5p, miR-363-3p and miR-150-5p in myelolipoma compared to the other two tumor groups by NGS. For ACC, we have found up-regulation of miR-184, miR-483-5p, miR-431-5p and miR-183-5p compared to myelolipoma and ACA. Validation by RT-qPCR, confirmed significant overexpression of miR-451a, miR-486-5p and miR-150-5p in myelolipomas relative to ACA and ACC, whereas significant overexpression of miR-184 and miR-183-5p was confirmed in ACC relative to the other 2 groups. The overexpression of miR-483-5p has not turned out to be significant in ACC relative to myelolipomas in the validation cohort. Conclusions: Overexpressed miR-451a, miR-486-5p and miR-150-5p might be potential tissue markers of adrenal myelolipoma. The lack of significance in the expression of miR-483-5p between ACC and myelolipoma is remarkable, as miR-483-5p has been considered to be the best marker of adrenal malignancy to date.
2018-04-07 | GSE112804 | GEO
Project description:CXCR4 expression by metastatic adrenocortical carcinoma is heterogeneous among patients and among lesions We used microarrays for 57 ACC metastases from 42 patients to evaluate gene expression in different lesions from same patients and over time, focusing on CXCR4 expression and other genes correlating with CXCR4 expression
2017-11-24 | GSE90713 | GEO
Project description:Adrenocortical carcinoma is a rare tumour with a poor prognosis. The currently available medical treatment options of adrenocortical cancer are limited. In the present study we examine the potential antitumoral effects of 9-cis-retinoic acid (9-cisRA) on the adrenocortical cancer cell line NCI-H295R. For the gene expression profiling, H295R cells were treated for 24h with 9cisRA at a final concentration of 2.5*10-5, 5*10-5 and 7.5*10-5 M and for the contol with the same amount of ethanol.
2013-02-10 | E-GEOD-43090 | biostudies-arrayexpress
Project description:Polybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants in a variety of commercial and household products. They have been detected in the environment and accumulate in mammalian tissues and fluids. PBDE toxicity is thought to be associated with endocrine disruption, developmental neurotoxicity and changes in fetal development. Although humans are exposed to PBDEs, our knowledge of the effects of PBDE metabolites on human cells with respect to health risk is insufficient. Two hydroxylated PBDEs (OH-PBDEs), 2-OH-BDE47 and 2-OH-BDE85, were investigated for their effects on cell viability/proliferation, DNA damage, cell cycle distribution and gene expression profiling in H295R adrenocortical carcinoma cells. We show that the two agents are cytotoxic in a dose-dependent manner only at micromolar concentrations, with 2-OH-BDE85 being more toxic than 2-OH-BDE47. However, no DNA damage was observed for either chemical, suggesting that the biological effects of OH-PBDEs occur primarily via non-genotoxic routes. Furthermore, no evidence of aryl hydrocarbon receptor (AHR)-mediated, dioxin-like toxicity was observed. Instead, we report that a micromolar concentration of OH-PBDEs induces transcriptional changes associated with endoplasmic reticulum stress and the unfolded protein response. We discuss whether OH-PBDE bioaccumulation could result in impairment of the adrenocortical secretory function.
2008-12-25 | GSE8588 | GEO
Project description:Adrenocortical carcinoma (ACC) is an aggressive endocrine tumor with a poor 5 year survival rate of 10-20%. We used expression profiling to assess the transcriptional changes associated with ACC as compared to normal adrenal glands with the goal of identifying new targets for treatment. Fourteen ACC tumors were profiled on both Affymetrix U133 Plus 2 or Agilent 22K Human Genome arrays; an additional six tumors were profiled on one or the other array. The data demonstrate a marked dysregulation of the cell cycle control, focused on sister chromatid adhesion and cytokinesis in the G2/M transistion. Genes associated with this pattern, and identified because of coordinate expression with CDC2, were capable of clustering ACC into two clusters that almost completely recapitulated histological grade. Exploration of the data sets by both Gene Set Enrichment Analysis and GeneGo Interactome analysis identified additional dysregulation of the IGF2-IGF1R axis, aside from IGF2 over-expression, as an early event present in low grade tumors. Additionally, p53 and MDM2 were consistently identified as drivers in leading edge analyses of the tumors, implicating the p53 pathway in ACC pathogenesis. Finally, over-expression of PTTG1, which encodes securin, and is involved in sister chromatid adhesion as well as negative regulation of p53, was associated with poor prognosis in our samples. Taken together, these data point toward a tumor type driven in part by dysregulated IGF2 signaling in the context of a lack of a functional p53 response, with potential vulnerabilities in the G2/M transition that may make viable therapeutic targets. RNA from fifteen adrenocortical carcinomas and a pool of four normal adrenal glands was extracted, labeled, and hybridized to Agilent Human 1A Oligo Microarray (v2) chips. The resulting data was first background subtracted. Each array then had the median intenisty subtracted from each channel, and finally both M and A values were quantile normalized across arrays. All calculations were done in R using the Bioconductor packages of marray and limma.
2013-11-21 | E-GEOD-19775 | biostudies-arrayexpress
Project description:Transcription factor 21 (TCF21) directly binds and regulates SF1 in tumor and normal adrenocortical cells, and both are involved in the development and steroidogenesis of the adrenal cortex. TCF21 is a tumor suppressor gene and its expression is reduced in malignant tumors. In adrenocortical tumors, it is less expressed in adrenocortical carcinomas (ACC) than in adrenocortical adenomas (ACA) and normal tissue. However, a comprehensive analysis to identify TCF21 targets have not yet been conducted in any type of cancer. In this study, we performed Chromatin Immunoprecipitation and Sequencing (ChIP-Seq) in adrenocortical carcinoma cell line (NCI-H295R) overexpressing TCF21, with the aim of identifying TCF21 new targets. The five most frequently identified sequences corresponded to the PRDM7, CNTNAP2, CACNA1B, PTPRN2 and KCNE1B genes. Validation experiments showed that, in NCI-H295R cells, TCF21 regulates gene expression positively in PRDM7 and negatively in CACNA1B. Recently, it was observed that the N-type calcium channel v2.2 (Cav2.2) encoded by CACNA1B gene is important in Angiotensin II signal transduction for corticosteroid biosynthesis in NCI-H295R adrenocortical carcinoma cells. Indeed, TCF21 inhibits CACNA1B and Cav2.2 expression in NCI-H295R. In addition, in a cohort of 55 adult patients with adrenocortical tumor, CACNA1B expression was higher in ACC than ACA, and was related to poor disease-free survival in ACC patients. These results suggest a mechanism of steroidogenesis control by TCF21 in adrenocortical tumor cells, in addition to the control observed through SF1 inhibition. Importantly, steroid production could impair tumor immunogenicity, contributing to the immune resistance described in adrenal cancer.
2022-06-30 | GSE179308 | GEO