Identification Of Gene Expression Profiles Research Articles

Single-cell RNA sequencing reveals common and unique gene expression profiles in primary CD4+ T cells latently infected with HIV under different conditions.

The latent HIV reservoir represents the major barrier to a cure. One curative strategy is targeting diseased cells for elimination based on biomarkers that uniquely define these cells. Single-cell RNA sequencing (scRNA-seq) has enabled the identification of gene expression profiles associated with disease at the single-cell level. Because HIV provirus in many cells during latency is not entirely silent, it became possible to determine gene expression patterns in a subset of cells latently infected with HIV. The primary objective of this study was the identification of the gene expression profiles of single latently infected CD4+ T cells using scRNA-seq. Different conditions of latency establishment were considered. The identified profiles were then explored to prioritize the identified genes for future experimental validation. To facilitate gene prioritization, three approaches were used. First, we characterized and compared the gene expression profiles of HIV latency established in different environments: in cells that encountered an activation stimulus and then returned to quiescence, and in resting cells that were infected directly via cell-to-cell viral transmission from autologous activated, productively infected cells. Second, we characterized and compared the gene expression profiles of HIV latency established with viruses of different tropisms, using an isogenic pair of CXCR4- and CCR5-tropic viruses. Lastly, we used proviral expression patterns in cells from people with HIV to more accurately define the latently infected cells in vitro. Our analyses demonstrated that a subset of genes is expressed differentially between latently infected and uninfected cells consistently under most conditions tested, including cells from people with HIV. Our second important observation was the presence of latency signatures, associated with variable conditions when latency was established, including cellular exposure and responsiveness to a T cell receptor stimulus and the tropism of the infecting virus. Common signatures, specifically genes that encode proteins localized to the cell surface, should be prioritized for further testing at the protein level as biomarkers for the ability to enrich or target latently infected cells. Cell- and tropism-dependent biomarkers may need to be considered in developing targeting strategies to ensure that all the different reservoir subsets are eliminated.

Identification of Gene Expression Profiles Associated with an Increased Risk of Post-Operative Recurrence in Crohn's Disease.

Ileocolonic resection is frequently needed in the course of Crohn's disease [CD] treatment and post-operative recurrence is extremely common. Our main objective was to analyse gene expression in the mucosa of CD patients at the time of surgery and at post-operative endoscopy, in order to identify predictors and mechanisms of early endoscopic recurrence. We conducted transcriptome analyses on ileal mucosa samples collected from inflamed sections of the surgical specimens [n = 200], from ileal resection margins [n = 149] and in the neo-terminal ileum 6 months after surgery [n = 122]; these were compared with non-inflammatory bowel disease controls [n = 25]. The primary endpoint was post-operative endoscopic recurrence at 6 months. We applied regression models to identify gene signatures predicting endoscopic recurrence. Chronic inflammation was associated with strong expression of inflammatory genes [IL-6, IL-8, IL-1B] and decreased expression of genes involved in metabolic processes, but with a high inter-individual heterogeneity. Gene signatures associated with early endoscopic recurrence were mainly characterized by upregulation of TNFα, IFNγ, IL23A and IL17A. Pathway analyses showed that upregulation of mitochondrial dysfunction within the inflamed sections and JAK/STAT at the ileal margin were predictive of post-operative recurrence. A combined model integrating these top pathway signatures improved the prediction of endoscopic recurrence [area under the curve of 0.79]. STAT3 phosphorylation at the surgical ileal margin was associated with severe recurrence at 6 months. We identified several biological pathways in surgical ileal mucosa specimens associated with an increased risk of disease recurrence. Integration of the JAK/STAT and mitochondrial dysfunction pathways in the clinical model improved the prediction of post-operative recurrence.

The Identification of Gene Expression Profiles Associated with Granulomatous Mastitis

Background: Granulomatous mastitis (GM) is a rare chronic inflammatory disease of the breast. The current therapeutic effects of the antibiotic therapy and surgical or immunomodulatory (steroid) treatment are normally poor due to the unclear etiology. Method: This study aimed to identify the differentially expressed mRNAs in GM tissues using RNA sequencing and further explored the functions of differentially expressed mRNAs resulting in GM. Moreover, we revealed the relationship between GM and breast cancer by shared highly expressed genes in GM tissues and breast cancer tissues. Results: A total of 12,115 mRNAs were analyzed in the whole expression profile, and 207 mRNAs (136 upregulated and 71 downregulated mRNAs) were differently expressed between the GM tissues and normal tissues. The enrichment analysis showed that the differentially expressed mRNAs were enriched in the biological processes and played a significant role in the immune system. Besides, the genes expressed significantly highly in breast cancer tissues are found to be enriched with GM genes, which may explain the similar clinical features between breast cancer and GM. We also found that the HSD11B1 gene which was differentially expressed in GM was used as drug target of prednisone, which is a common treatment for GM. Conclusion: This study is the first to use sequencing technology to elucidate the genetic mechanisms of GM. The finding of this study may have potential value in GM diagnosis and also provides potential drug targets for GM treatment.

Molecular approaches to equine sarcoids.

Sarcoids are the most commonly diagnosed skin tumours in equines. Bovine papillomaviruses (BPVs) are the primary causative agent of sarcoids. There has been intensive research to discover the molecular mechanisms that may contribute to the aetiopathogenesis of this disease and tumour suppressors and proto-oncogenes known to play a role in human neoplastic conditions have been investigated in equine sarcoids. Current approaches include the identification of gene expression profiles, characterising sarcoid and normal skin tissues, and an assessment of epigenetic alterations such as microRNA differential expression and DNA methylation status. This review focuses on selected groups of genes that contribute to the molecular mechanisms of sarcoid formation. These genes have the potential to complement current clinical examinations of equine sarcoid disease in diagnosis, prognosis, therapeutic response and screening.

PT181 - Identification of gene expression profile in low risk clear cell renal cell carcinoma to predict tumor progression

PT181 - Identification of gene expression profile in low risk clear cell renal cell carcinoma to predict tumor progression

Identification of gene expression profiles in Leishmania major infection by integrated bioinformatics analyses

Gene expression profiling in mouse models of leishmaniasis has given useful information to understand the molecular pathways active in lesions and to discover new diagnostic/therapeutic targets. Although the host response plays a critical role in protection from leishmaniasis and promoting disease severity, there are still unexplained aspects in the mechanism of non-healing cutaneous lesions, which need biomarkers for both targeted- therapy and diagnosis. To address this, transcriptional profiling of the skin lesions obtained from BALB/c mice infected with Leishmania major and healthy skin from naïve mice were evaluated by bioinformatics analysis, and then the results were validated by Revers Transcriptase-PCR. Five genes among the up-regulated differentially expressed genes named FCGR4, CCL4, CXCL9, Arg1 and IL-1β were found to have relatively high diagnostic value for CL due to L. major. Pathway analysis revealed that Triggering Receptor Expressed On Myeloid Cells 1 (TREM1) signaling pathways are active in cutaneous lesions, providing new insights for the understanding and treatment of leishmaniasis.

Identification of gene expression profiles and immune cell infiltration signatures between low and high tumor mutation burden groups in bladder cancer.

Bladder cancer is one of the most commonly diagnosed tumors and is results from the accumulation of somatic mutations in the DNA. Tumor mutation burden (TMB) has been associated with cancer immunotherapeutic response. In this study, we attempted to explore the correlation between TMB and cancer prognosis. Identify the different expressed genes and immune cell infiltration signatures between low and high TMB group. Mutation data, gene expression profiles and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. Patients were divided into high and low TMB groups, allowing differentially expressed genes (DEGs) to be identified. Functional enrichment and protein-protein interaction (PPI) network analysis were used to identify the functions of the DEGs. And immune cell infiltration signatures were evaluated by CIBERSORT algorithm. These results shown that high TMB was significantly associated with prognosis. We obtained a list of TMB related genes which may influence the infiltrations of immune cells. We also found a higher proportion of CD8 T cells, CD4 T cells and NK cells in the high TMB group. Our data suggest that higher TMB tends to promote the infiltrations of T cells and NK cells and patients with higher TMB may achieve a more favorable prognosis in bladder cancer.

Identification of gene expression profiles in myocardial infarction: a systematic review and meta-analysis

BackgroundMyocardial infarction (MI) is a multifactorial disease with complex pathogenesis, mainly the result of the interplay of genetic and environmental risk factors. The regulation of thrombosis, inflammation and cholesterol and lipid metabolism are the main factors that have been proposed thus far to be involved in the pathogenesis of MI. Traditional risk-estimation tools depend largely on conventional risk factors but there is a need for identification of novel biochemical and genetic markers. The aim of the study is to identify differentially expressed genes that are consistently associated with the incidence myocardial infarction (MI), which could be potentially incorporated into the traditional cardiovascular diseases risk factors models.MethodsThe biomedical literature and gene expression databases, PubMed and GEO, respectively, were searched following the PRISMA guidelines. The key inclusion criteria were gene expression data derived from case-control studies on MI patients from blood samples. Gene expression datasets regarding the effect of medicinal drugs on MI were excluded. The t-test was applied to gene expression data from case-control studies in MI patients.ResultsA total of 162 articles and 174 gene expression datasets were retrieved. Of those a total of 4 gene expression datasets met the inclusion criteria, which contained data on 31,180 loci in 93 MI patients and 89 healthy individuals. Collectively, 626 differentially expressed genes were detected in MI patients as compared to non-affected individuals at an FDR q-value = 0.01. Of those, 88 genes/gene products were interconnected in an interaction network. Totally, 15 genes were identified as hubs of the network.ConclusionsFunctional enrichment analyses revealed that the DEGs and that they are mainly involved in inflammatory/wound healing, RNA processing/transport mechanisms and a yet not fully characterized pathway implicated in RNA transport and nuclear pore proteins. The overlap between the DEGs identified in this study and the genes identified through genetic-association studies is minimal. These data could be useful in future studies on the molecular mechanisms of MI as well as diagnostic and prognostic markers.

Bioinformatics microarray analysis and identification of gene expression profiles associated with cirrhotic liver

Cirrhosis is the endpoint of liver fibrosis that is accompanied by limited regeneration capacity and complications and is the ultimate cause of death in many patients. Despite this, few studies have thoroughly looked at the gene expression profiles in the cirrhotic liver. Hence, this study aims to identify the genes that were differentially expressed in the cirrhotic liver and to explore the putative related signaling pathway and interaction networks. The gene expression profiles of cirrhotic livers and noncirrhotic livers were examined and compared using microarray gene analysis. Proteins encoded by the differentially expressed genes were analyzed for functional clustering and signaling pathway involvement using MetaCore bioinformatics analyses. The Gene Ontology analysis as well as the Kyoto encyclopedia of Genes and Genomes pathway analysis were also performed. A total of 213 significant genes were differentially expressed at more than a two-fold change in cirrhotic livers as compared to noncirrhotic livers. Of these, 105 upregulated genes and 63 downregulated genes were validated through MetaCore bioinformatics analyses. The signaling pathways and major functions of proteins encoded by these differentially expressed genes were further analyzed; results showed that the cirrhotic liver has a unique gene expression pattern related to inflammatory reaction, immune response, and cell growth, and is potentially cancer related. Our findings suggest that the microarray analysis may provide clues to the molecular mechanisms of liver cirrhosis for future experimental studies. However, further exploration of areas regarding therapeutic strategy might be possible to support metabolic activity, decrease inflammation, or enhance regeneration for liver cirrhosis.

Retraction Note to: Identification of gene expression profile in the rat brain resulting from acute alcohol intoxication.

This study aimed to identify gene expression profile in the rat brain resulting from acute alcohol intoxication (AAI). Eighteen SD rats were divided into the alcohol-treated group (n = 9) and saline control group (n = 9). Periorbital blood samples were taken to determine their blood alcohol content by gas chromatography. Tissue sections were analyzed by H and E staining and biochemical assays. Real-time reverse transcription PCR was used to validate microarray data. Statistical analysis was carried out using SPSS18.0 software (Version 18.0, SPSS Inc., Chicago, IL, USA). H and E staining demonstrated that alcohol-treated rats showed no obvious pathological changes in nerve cells compared with those in the control group. Biochemical tests revealed that alcohol-treated rats had lower superoxide dismutase activity than those in the control group (167.3 ± 10.3 U/mg vs. 189.2 ± 5.9 U/mg, P < 0.05). Furthermore, the malondialdehyde levels in alcohol-treated rats were higher than those in the control group (3.48 ± 0.24 mmol/mg vs. 2.51 ± 0.23 mmol/mg, P < 0.05). Microarray data presented 366 up-regulated genes and 300 down-regulated genes in the AAI rat brain. Gene ontology analysis identified 31 genes up-regulated and 39 down-regulated among all differentially expressed genes. Twenty-four pathways showed significant differences, including 12 pathways involved with up-regulated genes and 12 pathways involved with down-regulated genes. Selected genes showed significantly different expression in both alcohol-treated and control groups (P < 0.05). Gene expression analysis enabled clustering of alcohol intoxication-related genes by function. These genes expression may be potential targets for treatment or drug screening for acute alcohol intoxication.

Identification of gene expression profiles associated with prognostic groups of patients with Merkel cell carcinoma

Background Merkel cell carcinoma (MCC) is an aggressive form of skin cancer mostly caused by the Merkel cell polyomavirus [1]. MCC although rare in incidence is associated with poor prognosis. Gene expression studies (GES) have identified a number of genes that are associated with risk of developing MCC. However, their clinical utility to predict risk, response to treatment, or treatment toxicity, remains undefined. There is a need to better understand the biology of MCC and to develop potential new targets with regard to cancer risk and prognostic value [2]. Gene expression profiling and pathway association analysis on GES data can elucidate relevant biological processes, and identify new candidate target genes. Materials and methods We sought to identify differential gene expression and functional associations in MCC. Differentially expressed genes with a P value ≤ 0.05 and a fold change ≥ 2.5 between prognostic groups were identified and pathway association analysis was done for a total of 38 differentially expressed genes from a gene expression profiling study [3] with prognostic groups of MCC patients. The over representation of gene-based associations in each pathway was calculated using Fisher’s exact test. Results Pathways involved in neuropathic pain signaling, glutamate receptor signaling and synaptic long term potentiation were found to be highly enriched with associations. These results suggest that gene expressions associated with these pathways may contribute to MCC development and prognosis.

Identification of gene expression profile in the rat brain resulting from acute alcohol intoxication.

This study aimed to identify gene expression profile in the rat brain resulting from acute alcohol intoxication (AAI). Eighteen SD rats were divided into the alcohol-treated group (n = 9) and saline control group (n = 9). Periorbital blood samples were taken to determine their blood alcohol content by gas chromatography. Tissue sections were analyzed by H and E staining and biochemical assays. Real-time reverse transcription PCR was used to validate microarray data. Statistical analysis was carried out using SPSS18.0 software (Version 18.0, SPSS Inc., Chicago, IL, USA). H and E staining demonstrated that alcohol-treated rats showed no obvious pathological changes in nerve cells compared with those in the control group. Biochemical tests revealed that alcohol-treated rats had lower superoxide dismutase activity than those in the control group (167.3 ± 10.3 U/mg vs. 189.2 ± 5.9 U/mg, P < 0.05). Furthermore, the malondialdehyde levels in alcohol-treated rats were higher than those in the control group (3.48 ± 0.24 mmol/mg vs. 2.51 ± 0.23 mmol/mg, P < 0.05). Microarray data presented 366 up-regulated genes and 300 down-regulated genes in the AAI rat brain. Gene ontology analysis identified 31 genes up-regulated and 39 down-regulated among all differentially expressed genes. Twenty-four pathways showed significant differences, including 12 pathways involved with up-regulated genes and 12 pathways involved with down-regulated genes. Selected genes showed significantly different expression in both alcohol-treated and control groups (P < 0.05). Gene expression analysis enabled clustering of alcohol intoxication-related genes by function. These genes expression may be potential targets for treatment or drug screening for acute alcohol intoxication.

Identification of gene expression profile of neural crest-derived cells isolated from submandibular glands of adult mice

Neural crest cells in the embryo migrate to reach target sites as neural crest-derived cells (NCDCs) where they differentiate into a variety of derivatives. Some NCDCs are maintained in an undifferentiated state throughout the life of the animal and are considered to be a useful cell source for regenerative medicine. However, no established method to obtain NCDCs sufficient for regenerative medicine from adults with high purity has been presented, since their distribution in adult tissues is not fully understood. It is critical to identify reliable markers for NCDCs in adults, as the expressions of P0 and Wnt1, the most reliable NCDC markers, are shut off in the embryonic stage. To analyze the characteristics of NCDCs in adult tissues, we utilized a double transgenic mouse strain, P0-Cre/CAG-CAT-EGFP transgenic mice (P0 mice), in which NCDCs were shown to express EGFP and we were able to recognize GFP-positive cells in those. We focused on the submandibular glands (SMGs), which are known to be derived from the neural crest. GFP-positive cells were shown to be scattered like islands in the SMGs of adult P0 mice. We surgically removed SMGs from adult mice and digested samples into single cell suspensions. GFP-positive cells separated using flow cytometry expressed a high level of Sox10, a marker of embryonic neural crest cells, suggesting successful isolation of NCDCs. To identify candidate marker genes in isolated NCDCs, we performed DNA microarray analyses and real-time PCR analysis of GFP-positive and -negative cells isolated from P0 mice, then selected genes showing differential gene expression patterns. As compared to GFP-negative cells, GFP-positive cells expressed Gpr4 and Ednrb at higher levels, whereas Pdgfra and Pdgfrb were expressed at lower levels. Furthermore, DNA microarray analysis showed that GFP-positive cells were positive for aquaporin 5, a marker for acinar cells. Together, our results indicate that NCDCs in adult SMGs have characteristic gene expression profiles specially their cell surface molecules. Cell sorting using a combination of these specific cell surface proteins would be a useful strategy for isolation of NCDCs from SMGs with high purity.

Abstract A105: Identification of gene expression profiles associated with different types of breast adipose and their relationship to tumorigenesis

Abstract Background: Research over the past decade has shown the importance of the stroma in tumorigenesis, however, having long been thought to function only as an inert energy storage depot, the role of adipose tissue in tumor etiology has been largely ignored. Improved understanding of the role of adipose in tumor development and progression is crucial given the increasing rates of obesity and the use of autologous fat transfer in breast reconstruction. Methods: Adipose, adjacent to and distant from invasive breast tumors, was laser microdissected from 20 post-menopausal women, and from 20 post-menopausal women with non-malignant breast disease. Gene expression data were generated using U133 2.0 microarrays. After quality control and visualization steps, the data were analyzed to identify significant patterns of differential expression between adipose classes, at the individual gene and molecular pathway level. A subset of genes were further analyzed by qRT-PCR in out-of-sample adipose specimens. Results: Pathway analysis revealed significant differences in immune response between non-malignant, distant and tumor adjacent adipose. 141 genes were differentially expressed (FDR &amp;lt;0.05, &amp;gt;2-fold difference) between tumor-adjacent and non-malignant breasts including FCGR2A, FOLR2, LGMN and NLRP3. These four genes were also differentially expressed (FDR &amp;lt;0.05, &amp;gt;2-fold difference) between distant and non-malignant adipose. Within invasive breasts, no genes were differentially expressed using FDR &amp;lt;0.05, however, RRM2, PLA2G7, MMP9, MMP12, CHI3L1, SPP1 were expressed at &amp;gt;3-fold higher levels (P&amp;lt;0.05) in tumor-adjacent compared to distant adipose. Conclusions: Gene expression levels differ in breast adipose, depending on presence of or proximity to tumor cells. Tumor-adjacent and distant adipose from invasive breasts both exhibit increased expression in genes involved in the M2 anti-inflammatory response, suggesting that the microenvironment in an invasive breast has a decreased immune response compared to the non-malignant microenvironment. Genes expressed at higher levels in tumor-adjacent compared to distant adipose are associated with increased cellular proliferation, invasion, migration, angiogenesis and metastasis, suggesting that tumor-adjacent adipose promotes the growth and progression of the tumor. Together, these data suggest that adipose is not an inert component of the breast microenvironment but plays an active role in tumorigenesis. Citation Format: Lori Field, Brenda Deyarmin, Ryan van Laar, Craig Shriver, Rachel Ellsworth. Identification of gene expression profiles associated with different types of breast adipose and their relationship to tumorigenesis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A105.

Identification of gene expression profiles in pancreatic ductal adenocarcinoma. Clinical implications

Identification of gene expression profiles in pancreatic ductal adenocarcinoma. Clinical implications

Identification of Gene Expression Profiles Associated With Cortisol Secretion in Adrenocortical Adenomas

The cortisol secretion of adrenocortical adenomas can be either subtle or overt. The mechanisms leading to the autonomous hypersecretion of cortisol are unknown. The objective of the study was to identify the gene expression profile associated with the autonomous and excessive cortisol secretion of adrenocortical adenomas. The transcriptome of 22 unilateral adrenocortical adenomas (5 nonsecreting, 6 subclinical cortisol producing, 11 cortisol producing) was studied and correlated with cortisol secretion. Phosphodiesterase 8B (PDE8B) expression was measured by Western blot. Unsupervised clustering identified 2 groups of adenomas with a difference in secretion level (P = .008). Cluster 1 included only cortisol-producing adenomas (8 of 11), whereas cluster 2 was an admixture of the nonsecreting, the subclinical cortisol-secreting, and 3 of the 11 cortisol-secreting adenomas (Fisher exact, P = .002). This cluster was driven by genes related to cortisol secretion and to extracellular matrix. More than 3000 genes correlated with cortisol secretion. Among the positively correlated were the steroidogenic enzymes, genes involved in cholesterol metabolism, and glutathione S-transferases. Among the negatively correlated genes were genes related to transcripts translation and the transcription factor GATA-6. The PDE8B, which inactivates the protein kinase A pathway, unexpectedly showed the strongest positive correlation with cortisol secretion, confirmed by Western blot. The protein kinase A-activity to cAMP ratio was increased in adenomas with high PDE8B levels, suggesting counterregulation to limit downstream activation of the pathway. The transcriptome of adrenocortical adenomas reveals a major association with cortisol secretion and identifies specific groups of genes implicated in steroid secretion, suggesting that cAMP signaling alterations might be frequent in cortisol-secreting adenomas.

Identification of gene expression profiles in HeLa cells and HepG2 cells infected with Coxsackievirus B3

Viral infections of host cells cause multiple changes of cellular metabolism including immediate defense mechanisms as well as processes to support viral replication. Coxsackievirus B3 (CVB3) is a member of the Picornavirus family and is responsible for a wide variety of mild or severe infections including acute and chronic inflammations. Thereby, intracellular signaling can be changed very comprehensively. In order to compare the influence of CVB3 replication on gene expression pattern of two different cell lines, DNA microarray systems were used to study a set of 780 genes related to inflammation. Expression analysis of HeLa cells and HepG2 cells infected with CVB3 identified 34 genes whose mRNA levels were altered significantly upon infection. The expression of additional 16 genes in HepG2 cells and 31 genes in HeLa cells were found to be influenced during CVB3 replication as well. All genes expressed differentially were sorted with regard to their functions and interpreted in view of known contributors to the infection process. The activation of the tumor necrosis factor pathways by CVB3 represents one peculiar observation, including apoptosis, stress, and inflammation responses.

Abstract 4266: Identification of gene expression profiles associated with different types of breast adipose and their relationship to tumorigenesis

Abstract Background: Research over the past decade has shown the importance of the stroma in tumorigenesis, however, having long been thought to function only as an inert energy storage depot, the role of adipose tissue in tumorigenesis has been largely ignored. Improved understanding of the role of adipose in tumorigenesis is crucial given the increasing rates of obesity and the use of autologous fat transfer in breast reconstruction. Methods: Adipose, adjacent to and distant from invasive breast tumors, was laser microdissected from 20 post-menopausal women, and from 20 post-menopausal women with non-malignant breast disease. Gene expression data were generated using U133 2.0 microarrays. After quality control and visualization steps, the data were analyzed to identify significant patterns of differential expression between adipose classes, at the individual gene and molecular pathway level. Results: Pathway analysis revealed that immune response differs between non-malignant, distant and tumor adjacent adipose; this response is seen as a gradient with the largest response closest to the tumor. Gene expression differed significantly in adipose from invasive compared to non-malignant breasts with FCGR2A, FOLR2, LGMN, MARCO and NLRP3 expressed at significantly higher levels and HLA-DQB1 and HLA-DQA1 at significantly lower levels in adipose from invasive breasts. Within the invasive breasts, MMP9, PLA2G7, RRM2 and SPP1 were expressed at &amp;gt;3-fold higher levels in adjacent compared to distant adipose. Conclusions: Gene expression levels differ in breast adipose, depending on presence of or proximity to tumor cells. Adipose adjacent to the tumor demonstrated the largest immune response; this response may reflect a reaction to surgical insult from the original biopsy; however, response to surgical injury has been associated with increased ability to metastasize. In addition, within breasts with invasive breast cancer, genes involved in cellular proliferation, degradation of the extracellular matrix and angiogenesis were expressed at higher levels in adjacent compared to distant adipose. Together, these data suggest that adipose is not an inert component of the breast microenvironment but plays an active role in tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4266. doi:1538-7445.AM2012-4266

Identification of a Potential Ovarian Cancer Stem Cell Gene Expression Profile from Advanced Stage Papillary Serous Ovarian Cancer

Identification of gene expression profiles of cancer stem cells may have significant implications in the understanding of tumor biology and for the design of novel treatments targeted toward these cells. Here we report a potential ovarian cancer stem cell gene expression profile from isolated side population of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma. Affymetrix U133 Plus 2.0 microarrays were used to interrogate the differentially expressed genes between side population (SP) and main population (MP), and the results were analyzed by paired T-test using BRB-ArrayTools. We identified 138 up-regulated and 302 down-regulated genes that were differentially expressed between all 10 SP/MP pairs. Microarray data was validated using qRT-PCR and17/19 (89.5%) genes showed robust correlations between microarray and qRT-PCR expression data. The Pathway Studio analysis identified several genes involved in cell survival, differentiation, proliferation, and apoptosis which are unique to SP cells and a mechanism for the activation of Notch signaling is identified. To validate these findings, we have identified and isolated SP cells enriched for cancer stem cells from human ovarian cancer cell lines. The SP populations were having a higher colony forming efficiency in comparison to its MP counterpart and also capable of sustained expansion and differentiation in to SP and MP phenotypes. 50,000 SP cells produced tumor in nude mice whereas the same number of MP cells failed to give any tumor at 8 weeks after injection. The SP cells demonstrated a dose dependent sensitivity to specific γ-secretase inhibitors implicating the role of Notch signaling pathway in SP cell survival. Further the generated SP gene list was found to be enriched in recurrent ovarian cancer tumors.

The identification of gene expression profiles associated with progression of human diabetic neuropathy

Diabetic neuropathy is a common complication of diabetes. While multiple pathways are implicated in the pathophysiology of diabetic neuropathy, there are no specific treatments and no means to predict diabetic neuropathy onset or progression. Here, we identify gene expression signatures related to diabetic neuropathy and develop computational classification models of diabetic neuropathy progression. Microarray experiments were performed on 50 samples of human sural nerves collected during a 52-week clinical trial. A series of bioinformatics analyses identified differentially expressed genes and their networks and biological pathways potentially responsible for the progression of diabetic neuropathy. We identified 532 differentially expressed genes between patient samples with progressing or non-progressing diabetic neuropathy, and found these were functionally enriched in pathways involving inflammatory responses and lipid metabolism. A literature-derived co-citation network of the differentially expressed genes revealed gene subnetworks centred on apolipoprotein E, jun, leptin, serpin peptidase inhibitor E type 1 and peroxisome proliferator-activated receptor gamma. The differentially expressed genes were used to classify a test set of patients with regard to diabetic neuropathy progression. Ridge regression models containing 14 differentially expressed genes correctly classified the progression status of 92% of patients (P < 0.001). To our knowledge, this is the first study to identify transcriptional changes associated with diabetic neuropathy progression in human sural nerve biopsies and describe their potential utility in classifying diabetic neuropathy. Our results identifying the unique gene signature of patients with progressive diabetic neuropathy will facilitate the development of new mechanism-based diagnostics and therapies.