Different gene expression profiles in metastasizing midgut carcinoid tumors

2011 ◽  
Vol 18 (4) ◽  
pp. 479-489 ◽  
Author(s):  
Katarina Edfeldt ◽  
Peyman Björklund ◽  
Göran Åkerström ◽  
Gunnar Westin ◽  
Per Hellman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Metastases ◽  
Tumor Progression ◽  
Expression Profile ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Carcinoid Tumors ◽  
Disease Course ◽  
Primary Tumors ◽  
Midgut Carcinoid

The genetic events leading the progression of midgut carcinoid tumors are largely unknown. The disease course varies from patient to patient, and there is a lack of reliable prognostic markers. In order to identify genes involved in tumor progression, gene expression profiling was performed on tumor specimens. Samples comprised 18 primary tumors, 17 lymph node (LN) metastases, and seven liver metastases from a total of 19 patients. Patients were grouped according to clinical data and histopathology into indolent or progressive course. RNA was subjected to a spotted oligo microarray and B-statistics were performed. Differentially expressed genes were verified using quantitative real-time PCR. Self-organizing maps demonstrated three clusters: 11 primary tumors separated in one cluster, five LN metastases in another cluster, whereas all seven liver metastases, seven primary, and 12 LN metastases formed a third cluster. There was no correlation between indolent and progressive behavior. The primary tumors with Ki67 >5%, with low frequency of the carcinoid syndrome, and a tendency toward shorter survival grouped together. Primary tumors differed in expression profile from their associated LN metastases; thus, there is evidence for genetic changes from primary tumors to metastases.ACTG2, GREM2, REG3A, TUSC2, RUNX1, TPH1, TGFBR2, andCDH6were differentially expressed between clusters and subgroups of tumors. The expression profile that assembles tumors as being genetically similar on the RNA expression level may not be concordant with the clinical disease course. This study reveals differences in gene expression profiles and novel genes that may be of importance in midgut carcinoid tumor progression.

scholarly journals Non-Coding RNAs as Biomarkers of Tumor Progression and Metastatic Spread in Epithelial Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1839
Author(s):  
Karolina Seborova ◽  
Radka Vaclavikova ◽  
Lukas Rob ◽  
Pavel Soucek ◽  
Pavel Vodicka
Keyword(s):  
Ovarian Cancer ◽  
Tumor Progression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Distant Metastases ◽  
Regulatory Elements ◽  
Metastatic Spread ◽  
Response To Treatment ◽  
Primary Tumors ◽  
Non Coding Rnas

Ovarian cancer is one of the most common causes of death among gynecological malignancies. Molecular changes occurring in the primary tumor lead to metastatic spread into the peritoneum and the formation of distant metastases. Identification of these changes helps to reveal the nature of metastases development and decipher early biomarkers of prognosis and disease progression. Comparing differences in gene expression profiles between primary tumors and metastases, together with disclosing their epigenetic regulation, provides interesting associations with progression and metastasizing. Regulatory elements from the non-coding RNA families such as microRNAs and long non-coding RNAs seem to participate in these processes and represent potential molecular biomarkers of patient prognosis. Progress in therapy individualization and its proper targeting also rely upon a better understanding of interactions among the above-listed factors. This review aims to summarize currently available findings of microRNAs and long non-coding RNAs linked with tumor progression and metastatic process in ovarian cancer. These biomolecules provide promising tools for monitoring the patient’s response to treatment, and further they serve as potential therapeutic targets of this deadly disease.

The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2285-2290 ◽  
Author(s):  
James Z. Huang ◽  
Warren G. Sanger ◽  
Timothy C. Greiner ◽  
Louis M. Staudt ◽  
Dennis D. Weisenburger ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Germinal Center ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Germinal Center B Cell ◽  
Cell Gene Expression ◽  
Cell Gene

Recently we have identified subgroups of de novo primary diffuse large B-cell lymphoma (DLBCL) based on complementary DNA microarray-generated gene expression profiles. To correlate the gene expression profiles with cytogenetic abnormalities in these DLBCLs, we examined the occurrence of the t(14;18)(q32;q21) in the 2 distinctive subgroups of DLBCL: one with the germinal center B-cell gene expression signature and the other with the activated B cell–like gene expression signature. The t(14;18) was detected in 7 of 35 cases (20%). All 7 t(14;18)-positive cases had a germinal center B-cell gene expression profile, representing 35% of the cases in this subgroup, and 6 of these 7 cases had very similar gene expression profiles. The expression of bcl-2 and bcl-6 proteins was not significantly different between the t(14;18)-positive and -negative cases, whereas CD10 was detected only in the group with the germinal center B-cell expression profile, and CD10 was most frequently expressed in the t(14;18)-positive cases. This study supports the validity of subdividing DLBCL into 2 major subgroups by gene expression profiling, with the t(14;18) being an important event in the pathogenesis of a subset of DLBCL arising from germinal center B cells. CD10 protein expression is useful in identifying cases of DLBCL with a germinal center B-cell gene expression profile and is often expressed in cases with the t(14;18).

scholarly journals The single-cell transcriptional landscape of lung carcinoid tumors

2021 ◽  
Author(s):  
Philip Bischoff ◽  
Alexandra Trinks ◽  
Jennifer Wiederspahn ◽  
Benedikt Obermayer ◽  
Jan Patrick Pett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Carcinoid Tumor ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Carcinoid Tumors ◽  
Cellular Composition ◽  
Cell Gene Expression ◽  
Cell Gene ◽  
Lung Carcinoid

AbstractLung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread while no consensus treatment exists for metastasized carcinoids. Several recent single-cell studies have provided detailed insights into the cellular heterogeneity of more common lung cancers, such as adeno- and squamous cell carcinoma. However, the characteristics of lung carcinoids on the single-cell level are yet completely unknown.To study the cellular composition and single-cell gene expression profiles in lung carcinoids, we applied single-cell RNA sequencing to three lung carcinoid tumor samples and normal lung tissue. The single-cell transcriptomes of carcinoid tumor cells reflected intertumoral heterogeneity associated with clinicopathological features, such as tumor necrosis and proliferation index. The immune microenvironment was specifically enriched in noninflammatory monocyte-derived myeloid cells. Tumor-associated endothelial cells were characterized by distinct gene expression profiles. A spectrum of vascular smooth muscle cells and pericytes predominated the stromal microenvironment. We found a small proportion of myofibroblasts exhibiting features reminiscent of cancer-associated fibroblasts. Stromal and immune cells exhibited potential paracrine interactions which may shape the microenvironment via NOTCH, VEGF, TGFβ and JAK/STAT signaling. Moreover, single-cell gene signatures of pericytes and myofibroblasts demonstrated prognostic value in bulk gene expression data.Here, we provide first comprehensive insights into the cellular composition and single-cell gene expression profiles in lung carcinoids, demonstrating the non-inflammatory and vessel-rich nature of their tumor microenvironment, and outlining relevant intercellular interactions which could serve as future therapeutic targets.

Early T-Cell Precursor-ALL in Adult T-ALL.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 911-911 ◽  
Author(s):  
Martin Neumann ◽  
Sandra Heesch ◽  
Stefan Schwartz ◽  
Nicola Gökbuget ◽  
Dieter Hoelzer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Real Time ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Real Time Pcr ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Gene Expression Profiles ◽  
Study Group

Abstract Abstract 911 Introduction: Recently, a small subgroup of pediatric acute T-lymphoblastic leukemia (T-ALL) was described, which is closely associated with the gene expression profile of early T-cell precursors (ETPs). This subtype, termed ETP-ALL, showed a highly unfavorable outcome compared to non-ETP(='typical')-ALL. Based on the results of Coustan-Smith et al. (Lancet Oncology, 2009), the Italian national study Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) and St-Jude Children's hospital modified their treatment in children with ETP-ALL to a more intensive regime including stem cell transplantation. ETP-ALL is characterized by a specific immunophenotype (CD1a-, CD8-, CD5weak with expression of stem cell or myeloid markers). Here we explored the existence of ETP-ALL in adults and further studied the molecular characteristics of this specific T-ALL subtype. Patients and methods: We examined the gene expression profiles of 86 adult T-ALL patients obtained from the Microarray Innovations in LEukemia (MILE) multicenter study (HG-U133 Plus 2.0, Affymetrix, Haferlach et al., JCO in press). In addition, bone marrow of 296 patients from the German Acute Lymphoblastic Leukemia Multicenter Study Group (GMALL) were analyzed by flow cytometry and expression levels of BAALC, IGFBP7, MN1, and WT1 were determined by real-time-PCR. Results: Using the published list of differentially expressed genes in ETPs (Coustan-Smith et al. 2009) we performed unsupervised clustering analyses of the 86 T-ALL samples. A cluster of 17 samples (19.8%) displayed an ETP-associated gene expression profile and were defined as ETP-ALL. Comparing the gene expression profiles of ETP-ALL and typical T-ALL, 2065 probe sets were differentially expressed in ETP-ALL (FDR 0.05). In addition to genes used for classification, we also identified genes known to be involved in the pathogenesis of T-ALL (e.g. PROM1, BCL2, LMO2, LYL1). In particular, stem cell associated genes such as, BAALC (2.52-fold, p=0.003), IGFBP7 (2.76-fold, p=0.002) or MN1 (3.41-fold, p<0.001) were upregulated in ETP-ALL, whereas HOX11 (45-fold, p=0.004), a marker for thymic T-ALL, was downregulated. An independent cohort of 297 patient samples from the GMALL study group was examined by flow cytometry and real-time PCR. 19 (6.4%) samples revealed the ETP-ALL immunophenotype. As expected, all patient samples were found in the group of early T-ALL, representing 23.5% of all early T-ALLs. There was a significant correlation between a lower leukocyte count at first diagnosis and the classification of ETP-ALL (p=0.001). Gene expression measured by real-time-PCR was performed for genes associated with poor outcome in T-ALL: BAALC (2.11-fold, p<0.001) and IGFBP7 (3.59-fold, p=0.003) were significantly upregulated in the group of ETP-ALL. Similarly, the genes MN1 (4.52-fold, p<0.001) and WT1 (2.76-fold, p=0.036), described as poor prognostic markers in cytogenetically normal AML, were also upregulated in ETP-ALL. Conclusion: In adult T-ALL, a subset of patients shares the gene expression profil and immunophenotype of ETP-ALL, which is in line with recent findings in pediatric patients. The gene expression profile of this subset is significantly correlated to stem cell associated markers predictive for inferior outcome in T-ALL. Interestingly, adverse factors in CN-AML are also aberrantly expressed in ETP-ALL suggesting a myeloid origin of ETPs and indicating a closer relationship between ETP-ALL and AML. The prognostic impact and the determination of the most appropiate set of markers needs to be further investigated. These results support the GMALL strategy to regard early T-ALL patients as high risk with assignment to stem cell transplantation. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Equity Ownership.

Combining Gene Expression Profiles and Clinical Parameters for Risk Stratification in Medulloblastomas

2004 ◽  
Vol 22 (6) ◽  
pp. 994-998 ◽  
Author(s):  
Ana Fernandez-Teijeiro ◽  
Rebecca A. Betensky ◽  
Lisa M. Sturla ◽  
John Y.H. Kim ◽  
Pablo Tamayo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Expression Profiles ◽  
Univariate Analysis ◽  
Gene Expression Profiles ◽  
Clinical Parameters ◽  
Histologic Subtype ◽  
Clinical Variables ◽  
Outcome Predictions

Purpose Stratification of risk in patients with medulloblastoma remains a challenge. As clinical parameters have been proven insufficient for accurately defining disease risk, molecular markers have become the focus of interest. Outcome predictions on the basis of microarray gene expression profiles have been the most accurate to date. We ask in a multivariate model whether clinical parameters enhance survival predictions of gene expression profiles. Patients and Methods In a cohort of 55 young patients (whose medulloblastoma samples have been analyzed previously for gene expression profile), associations between clinical and gene expression variables and survival were assessed using Cox proportional hazards models. Available clinical variables included age, stage (ie, the presence of disseminated disease at diagnosis), sex, histologic subtype, treatment, and status. Results Univariate analysis demonstrated expression profiles to be the only significant clinical prognostic factor (P = .03). In multivariate analysis, gene expression profiles predicted outcome independent of other criteria. Clinical criteria did not significantly contribute additional information for outcome predictions, although an exploratory analysis noted a trend for decreased survival of patients with metastases at diagnosis but favorable gene expression profile. Conclusion Gene expression profiling predicts medulloblastoma outcome independent of clinical variables. These results need to be validated in a larger prospective study.

scholarly journals Global gene expression profiling in mouse plasma cell tumor precursor and bystander cells reveals potential intervention targets for plasma cell neoplasia

Blood ◽  
2012 ◽  
Vol 119 (4) ◽  
pp. 1018-1028 ◽  
Author(s):  
Jason LeGrand ◽  
Eun Sung Park ◽  
Hongyang Wang ◽  
Shalu Gupta ◽  
James D. Owens ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Progression ◽  
Plasma Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mrna Translation ◽  
Global Gene Expression ◽  
Cell Tumor ◽  
Plasma Cell Tumor

Abstract Tumor progression usually proceeds through several sequential stages, any of which could be targets for interrupting the progression process if one understood these steps at the molecular level. We extracted nascent plasma cell tumor (PCT) cells from within inflammatory oil granulomas (OG) isolated from IP pristane-injected BALB/c.iMycEμ mice at 5 different time points during tumor progression. We used laser capture microdissection to collect incipient PCT cells and analyzed their global gene expression on Affymetrix Mouse Genome 430A microarrays. Two independent studies were performed with different sets of mice. Analysis of the expression data used ANOVA and Bayesian estimation of temporal regulation. Genetic pathway analysis was performed using MetaCore (GeneGo) and IPA (Ingenuity). The gene expression profiles of PCT samples and those of undissected OG samples from adjacent sections showed that different genes and pathways were mobilized in the tumor cells during tumor progression, compared with their stroma. Our analysis implicated several genetic pathways in PCT progression, including biphasic (up- and then down-regulation) of the Spp1/osteopontin-dependent network and up-regulation of mRNA translation/protein synthesis. The latter led to a biologic validation study that showed that the AMPK-activating diabetes drug, metformin, was a potent specific PCT inhibitor in vitro.

scholarly journals Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets

2006 ◽  
Vol 13 (2) ◽  
pp. 541-558 ◽  
Author(s):  
G Capurso ◽  
S Lattimore ◽  
T Crnogorac-Jurcevic ◽  
F Panzuto ◽  
M Milione ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Metastases ◽  
Cell Lines ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Therapeutic Targets ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Striking Similarity ◽  
Metastatic Lesions

The intrinsic nature of tumour behaviour (stable vs progressive) and the presence of liver metastases are key factors in determining the outcome of patients with a pancreatic endocrine tumour (PET). Previous expression profile analyses of PETs were limited to non-homogeneous groups or to primary lesions only. The aim of this study was to investigate the gene expression profiles of a more uniform series of sporadic, non-functioning (NF) PETs with progressive disease and, for the first time, their liver metastases, on the Affymetrix human genome U133A and B GeneChip set. Thirteen NF PET samples (eight primaries and five liver metastases) from ten patients with progressive, metastatic disease, three cell lines (BON, QGP and CM) and four purified islet samples were analysed. The same samples were employed for confirmation of candidate gene expression by means of quantitative RT-PCR, while a further 37 PET and 15 carcinoid samples were analysed by immunohistochemistry. Analysis of genes differentially expressed between islets and primaries and metastases revealed 667 up- and 223 down-regulated genes, most of which have not previously been observed in PETs, and whose gene ontology molecular function has been detailed. Overexpression of bridging integrator 1 (BIN1) and protein Z dependent protease inhibitor (SERPINA10) which may represent useful biomarkers, and of lymphocyte specific protein tyrosine kinase (LCK) and bone marrow stromal cell antigen (BST2) which could be used as therapeutic targets, has been validated. When primary tumours were compared with metastatic lesions, no significantly differentially expressed genes were found, in accord with cluster analysis which revealed a striking similarity between primary and metastatic lesions, with the cell lines clustering separately. We have provided a comprehensive list of differentially expressed genes in a uniform set of aggressive NF PETs. A number of dysregulated genes deserve further in-depth study as potentially promising candidates for new diagnostic and treatment strategies. The analysis of liver metastases revealed a previously unknown high level of similarity with the primary lesions.

Translation of gene expression profiles into a nine antibody IHC multivariate index assay for colorectal carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21042-21042
Author(s):  
M. T. Schreeder ◽  
R. S. Seitz ◽  
R. Beck ◽  
B. Z. Ring ◽  
D. T. Ross
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Early Stage Disease ◽  
Primary Tumors ◽  
Pathologic Stage ◽  
Predicting Outcome ◽  
Antibody Panel

21042 Introduction: Pathologic stage is the most powerful predictor of outcome in colorectal cancer. However, in early stage disease there continues to be a need for better identification of patients at high risk of disease progression after surgical resection. We have undertaken a large scale effort translating gene expression profiles into immunohistochemical biomarkers that classify carcinoma in novel ways. Herein we report the identification of a colorectal tailored antibody “panel of diversity” that distinguishes tumor heterogeneity and propose a multivariate index assay (MIA) for predicting outcome. Methods: 744 stage I-III consecutive colon cancer patients treated by the CCIH between 1992 and 2000 were identified. Clinical followup through 2005 was obtained from the tumor registry and verified by chart review . Tissue micorarrays (TMA) were constructed from these patients resected primary tumors. Over 700 antibodies targeted by carcinoma gene expression experiments or literature review were first screened on a 30 case TMA. Of these, 34 were selected as showing subjectively high quality stains and the ability to classify patient populations. These antibodies were used to stain the clinical TMA and scored using a semi-quantitative scale. We used a number of approaches including Cox, RPART, and Bayesian to derive candidate MIA's to predict recurrence. Results: 13 antibodies showed a significant or near significant association with either overall recurrence or recurrence at 5 years. We have previously shown these antibodies to have similar prognostic abilities in other solid tumor carcinomas. We propose a model combining nine markers (p53, CCNA2, TFF3, RERG, AKR1C1, TLE3, IRX3, SYP, TTC7) as an MIA for predicting outcome in Stage II patients. The model is independent of pathologic stage. Conclusions: This colon tailored antibody ‘panel of diversity’ is a tool for characterizing the biologic diversity in colon cancer cohorts. The identification of nine prognostic markers that can be effectively combined using an MIA suggests that combination of multiple markers will be useful for developing sensitive and specific prognostic assays. The model proposed herein should be validated using additional cohorts to evaluate its overall clinical utility. No significant financial relationships to disclose.

RNA-seq analysis of non-muscular invasive bladder cancer to reveal different gene expression profiles between smoking and non-smoking patients.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 478-478
Author(s):  
Zhichao Fu ◽  
Shenghua Liu ◽  
Jianfei Wang ◽  
Ning He ◽  
Yadong Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Tumor Progression ◽  
Urothelial Carcinoma ◽  
Differentially Expressed Genes ◽  
Poor Prognosis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Rna Seq

478 Background: Bladder cancer is the ninth most common malignancy in the world, approximately 75% of patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). Smoking has been established to be a carcinogenic risk factor of bladder cancer. Nevertheless, the detailed relationship between smoking and progression of NMIBC are poorly understood. In this study, we revealed high expressed genes in smoking patients were significantly related to tumor progression in NMIBC patients. Methods: A total of 54 NMIBC patients including 19 never smokers and 35 smokers (current smokers and previous smokers) were enrolled in this study.The gene expression profiles were obtained by RNA-seq and the differentially expressed genes between smoking and non-smoking patients were identified using DESeq2 .The further analysis of the association between genes expression and patient survival in NMIBC cohorts(Jakob et al., 2016)and IMvigor 210 cohorts(Jonathan et al., 2016)by Kaplan-Meier survival estimate. Results: We identified 46 differentially expressed genes (p<0.05) in smoking and non-somking NMIBC patients. IDO1 and KRT14 gene, which related to bladder cancer progression and poor prognosis, was identified significantly higher expressed in somking group compared with non-smoking and they have a logFC of 2.6,3.9 with FDR 1.83E-5,3.40E-5 respectively. The expression of other genes, including KRT6A, CASP14, SERPINA1, MYO3A and IL20RB, were significantly higher in smoking patients compared to non-somking. Notably, survival data analysis from 476 NMIBC cohorts showed that IL20RB had a significant relationship with poor PFS(p = 0.021) and in the Mvigor 210 Cohort including 310 advanced or metastatic urothelial carcinoma patients treated with atezolizumab, we found that the high expression of IL20RB was significantly related to poor OS(p = 0.002). Conclusions: We identified 14 genes related to tumor progression were significantly higher in smoking NMIBC patients than in non-smoking. Among these genes, the expression of IL20RB was related to the poor prognosis of NMIBC, and it may correlates with reduced clinical benefit of immunotherapeutic in patients with urothelial carcinoma.

Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer

2015 ◽  
Vol 362 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Wendy Onstenk ◽  
Anieta M. Sieuwerts ◽  
Marleen Weekhout ◽  
Bianca Mostert ◽  
Esther A. Reijm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metastatic Breast ◽  
Primary Tumors
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