Identification of novel neuroendocrine-specific tumour genes.
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ABSTRACT:
SUBMITTER: Hofsli E
PROVIDER: S-EPMC2570516 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Targeting growth-regulatory pathways is a promising approach in cancer treatment. A prerequisite to the development of such therapies is characterisation of tumour growth regulation in the particular tumour cell type of interest. In order to gain insight into molecular mechanisms underlying proliferative responses in neuroendocrine (NE) gastrointestinal (GI) tumours, we investigated gene expression in human carcinoid BON cells after exposure to gastrin, hepatocyte growth factor (HGF), pituitary adenylate cyclase-activating polypeptide or epidermal growth factor. We particularly focused on gastrin- and HGF-induced gene expression, and identified 95 gastrin- and 101 HGF-responsive genes. The majority of these genes are known mediators of processes central in tumour biology, and a number of them have been associated with poor prognosis and metastasis in cancer patients. Furthermore, we identified 12 genes that were regulated by all four factors, indicating that they may be universally regulated during NE GI tumour cell proliferation. Our findings provide useful hypotheses for further studies aimed to search for new therapeutic targets as well as tumour markers in NE GI tumours.
| S-EPMC2361991 | biostudies-literature
Project description:Neuroendocrine liver metastases (LM-NEN) develop in a considerable proportion of patients with gastroenteropancreatic neuroendocrine neoplasms. There is a paucity of experimental models that accurately recapitulate this complex metastatic human liver microenvironment precluding scientific and clinical advancements. Here, we describe the development of a novel personalised immunocompetent precision cut tumour slice (PCTS) model for LM-NEN using resected human liver tissue. The histological assessment throughout the culture demonstrated that slices maintain viability for at least 7 days and retain the cellular heterogeneity of the original tumour. Essential clinical features, such as patient-specific histoarchitecture, tumour grade, neuroendocrine differentiation and metabolic capacity, are preserved in the slices. The PCTS also replicate the tumor-specific immunological profile as shown by the innate and adaptive immunity markers analysis. Furthermore, the study of soluble immune checkpoint receptors in the culture supernatants proves that these immunomodulators are actively produced by LM-NEN and suggests that this process is epithelium-dependent. This model can be employed to investigate these pathways and provides a powerful platform for mechanistic, immunological and pre-clinical studies.
| S-EPMC9326114 | biostudies-literature
Project description:BackgroundOne of the important goals of microarray research is the identification of genes whose expression is considerably higher or lower in some tissues than in others. We would like to have ways of identifying such tissue-specific genes.ResultsWe describe a method, ROKU, which selects tissue-specific patterns from gene expression data for many tissues and thousands of genes. ROKU ranks genes according to their overall tissue specificity using Shannon entropy and detects tissues specific to each gene if any exist using an outlier detection method. We evaluated the capacity for the detection of various specific expression patterns using synthetic and real data. We observed that ROKU was superior to a conventional entropy-based method in its ability to rank genes according to overall tissue specificity and to detect genes whose expression pattern are specific only to objective tissues.ConclusionROKU is useful for the detection of various tissue-specific expression patterns. The framework is also directly applicable to the selection of diagnostic markers for molecular classification of multiple classes.
| S-EPMC1501047 | biostudies-literature
Project description:(This section will be revisited in good time prior to publication, for final approval) Research within the field of functional genomics provides a more profound understanding of living organisms, by elucidating the interaction between genes and gene products. This is of increasing importance in many fields, and especially within cancer research. With the use of microarray technology, the gene expression of a vast number of genes can be measured simultaneously. This allows us insight into tumor biology, and an opportunity to obtain knowledge of diagnostic and prognostic value, as well as hints towards the causes of cancer. In this study the gene expression in a selection of human neuroendocrine (NE) and non-neuroendocrine tumor cell lines were compared. Both qualitative and quantitative methods were applied to get an insight into the NE tumor biology. NE cells are found in practically every organ and tissue in the body and are assigned to synthesize peptide hormones and take up amino acids and transform these into biogenic amines by carboxylation. NE tumors arise after malignant transformation of neuroendocrine cells and are usually highly differentiated and have a low growth rate, which makes this a high prevalence tumor type. These rather rare tumors characteristically express NE markers, such as chromogranin A, and contains characteristic dense-secretory core granules. By using cDNA microarray analysis, the gene expression profiles of various NE tumor cell lines (e. g. carcinoid, neuroblastoma, medullary thyroid carcinoma and endocrine pancreatic tumor) were compared with those of non-NE tumor cells. As a reference the commercially available Universal human RNA reference (Stratagene) was used. Verification of the results were done by real time RT-PCR analysis after the NE nature of the cell lines was stated by immunohistochemical, electron microscopic and light microscopic examinations. A large number of genes were differentially expressed in NE cell lines vs. the non-NE cell lines, and were found to be of interest in NE tumor biology. Some of these genes were previously known in NE tumor biology, whereas the vast majority of the specified genes are novel in the context of NE tumor biology. Genes with little previous information were also identified and thought to be an asset in the search of new NE markers. A feasible prospective of the study would be expansion with additional samples cell lines and a more thorough verification with real time RT-PCR analysis. This would enhance the credibility and thus the utility of the findings. Future studies on the biological functions of the candidate genes and the mechanisms of their regulation, will hopefully enable suggestions of new NE markers of prognostic or diagnostic value, and eventually new drug targets. Keywords: neuroendocrine, neuroendocrine markers, gene expression profiling, cDNA microarray The hybridisation was performed by an experienced laboratory technician Eli Helge, (Dept. of Laboratory Medicine, Children`s and Women`s health, NTNU) at the microarray core facility. Three separate runs with 10, 11 and 3 slides was needed to obtain the 20 hybridisations (dyeswap x 10 cell lines) planned for this study. Of the 10 cell lines 6 were neuroendocrine and 4 were non-neuroendocrine. For comparison between these two groups the universal human reference RNA (Stratagene) was used as the "control" on each slide. An adapted version of the 3DNA Array 350 protocol (Genisphere) was used. The slides were scanned with a ScanArrayTMExpressHT (Packard BioScience) twice immediately after the hybridisation was completed to avoid photo bleaching of the fluorescent dyes.
| S-ECPF-GEOD-4328 | biostudies-other
Project description:(This section will be revisited in good time prior to publication, for final approval) Research within the field of functional genomics provides a more profound understanding of living organisms, by elucidating the interaction between genes and gene products. This is of increasing importance in many fields, and especially within cancer research. With the use of microarray technology, the gene expression of a vast number of genes can be measured simultaneously. This allows us insight into tumor biology, and an opportunity to obtain knowledge of diagnostic and prognostic value, as well as hints towards the causes of cancer. In this study the gene expression in a selection of human neuroendocrine (NE) and non-neuroendocrine tumor cell lines were compared. Both qualitative and quantitative methods were applied to get an insight into the NE tumor biology. NE cells are found in practically every organ and tissue in the body and are assigned to synthesize peptide hormones and take up amino acids and transform these into biogenic amines by carboxylation. NE tumors arise after malignant transformation of neuroendocrine cells and are usually highly differentiated and have a low growth rate, which makes this a high prevalence tumor type. These rather rare tumors characteristically express NE markers, such as chromogranin A, and contains characteristic dense-secretory core granules. By using cDNA microarray analysis, the gene expression profiles of various NE tumor cell lines (e. g. carcinoid, neuroblastoma, medullary thyroid carcinoma and endocrine pancreatic tumor) were compared with those of non-NE tumor cells. As a reference the commercially available Universal human RNA reference (Stratagene) was used. Verification of the results were done by real time RT-PCR analysis after the NE nature of the cell lines was stated by immunohistochemical, electron microscopic and light microscopic examinations. A large number of genes were differentially expressed in NE cell lines vs. the non-NE cell lines, and were found to be of interest in NE tumor biology. Some of these genes were previously known in NE tumor biology, whereas the vast majority of the specified genes are novel in the context of NE tumor biology. Genes with little previous information were also identified and thought to be an asset in the search of new NE markers. A feasible prospective of the study would be expansion with additional samples cell lines and a more thorough verification with real time RT-PCR analysis. This would enhance the credibility and thus the utility of the findings. Future studies on the biological functions of the candidate genes and the mechanisms of their regulation, will hopefully enable suggestions of new NE markers of prognostic or diagnostic value, and eventually new drug targets. Keywords: neuroendocrine, neuroendocrine markers, gene expression profiling, cDNA microarray The hybridisation was performed by an experienced laboratory technician Eli Helge, (Dept. of Laboratory Medicine, Children`s and Women`s health, NTNU) at the microarray core facility. Three separate runs with 10, 11 and 3 slides was needed to obtain the 20 hybridisations (dyeswap x 10 cell lines) planned for this study. Of the 10 cell lines 6 were neuroendocrine and 4 were non-neuroendocrine. For comparison between these two groups the universal human reference RNA (Stratagene) was used as the "control" on each slide. An adapted version of the 3DNA Array 350 protocol (Genisphere) was used. The slides were scanned with a ScanArrayTMExpressHT (Packard BioScience) twice immediately after the hybridisation was completed to avoid photo bleaching of the fluorescent dyes.
2010-06-24 | E-GEOD-4328 | biostudies-arrayexpress
Project description:CALM-NET was a phase IV exploratory study in the UK that aimed to evaluate if the presence of circulating tumour cells (CTCs) at baseline predicted symptomatic response in patients with midgut neuroendocrine tumours (NETs) treated with lanreotide autogel (LAN). Adults with functional, well/moderately differentiated (Ki-67 <20%) midgut NETs received LAN 120 mg/28 days for 1 year. CTCs were present in blood if enumeration was >0. Primary endpoint was the clinical value of baseline CTCs to predict symptomatic response (decrease in diarrhoea or flushing of ≥50% frequency, or ≥1 severity level). Other endpoints included progression-free survival (PFS) and correlations between plasma and urinary biomarkers (including 5-hydroxyindoleacetic acid [5-HIAA]). Fifty patients were enrolled; 40 completed the study. Baseline CTCs were present in 22 (45.8%) patients (missing baseline CTC status n = 2). Overall, 87.5% (95% confidence interval [CI]: 73.9; 94.5) of patients had a symptomatic response; a 5.9-fold higher odds of symptomatic response in patients without CTC versus patients with CTC at baseline was observed, although this was not statistically significant (odds ratio: 0.17 [95% CI: 0.02; 1.65], p = .126). One-year PFS rate was 66.4% (95% CI: 48.8; 79.2). Biomarker concentrations did not correlate to baseline CTC status. However, there was a strong correlation between plasma and urinary 5-HIAA (Spearman correlation coefficients ≥0.87 [p < .001], all time points). In conclusion, patients without CTC at baseline may be more likely to achieve a symptomatic response following LAN treatment than patients with CTC. Plasma 5-HIAA correlated with urinary 5-HIAA during LAN treatment. ClinicalTrials.gov identifier: NCT02075606.
| S-EPMC9285714 | biostudies-literature
Project description:(This section will be revisited in good time prior to publication, for final approval) Research within the field of functional genomics provides a more profound understanding of living organisms, by elucidating the interaction between genes and gene products. This is of increasing importance in many fields, and especially within cancer research. With the use of microarray technology, the gene expression of a vast number of genes can be measured simultaneously. This allows us insight into tumor biology, and an opportunity to obtain knowledge of diagnostic and prognostic value, as well as hints towards the causes of cancer. In this study the gene expression in a selection of human neuroendocrine (NE) and non-neuroendocrine tumor cell lines were compared. Both qualitative and quantitative methods were applied to get an insight into the NE tumor biology. NE cells are found in practically every organ and tissue in the body and are assigned to synthesize peptide hormones and take up amino acids and transform these into biogenic amines by carboxylation. NE tumors arise after malignant transformation of neuroendocrine cells and are usually highly differentiated and have a low growth rate, which makes this a high prevalence tumor type. These rather rare tumors characteristically express NE markers, such as chromogranin A, and contains characteristic dense-secretory core granules. By using cDNA microarray analysis, the gene expression profiles of various NE tumor cell lines (e. g. carcinoid, neuroblastoma, medullary thyroid carcinoma and endocrine pancreatic tumor) were compared with those of non-NE tumor cells. As a reference the commercially available Universal human RNA reference (Stratagene) was used. Verification of the results were done by real time RT-PCR analysis after the NE nature of the cell lines was stated by immunohistochemical, electron microscopic and light microscopic examinations. A large number of genes were differentially expressed in NE cell lines vs. the non-NE cell lines, and were found to be of interest in NE tumor biology. Some of these genes were previously known in NE tumor biology, whereas the vast majority of the specified genes are novel in the context of NE tumor biology. Genes with little previous information were also identified and thought to be an asset in the search of new NE markers. A feasible prospective of the study would be expansion with additional samples cell lines and a more thorough verification with real time RT-PCR analysis. This would enhance the credibility and thus the utility of the findings. Future studies on the biological functions of the candidate genes and the mechanisms of their regulation, will hopefully enable suggestions of new NE markers of prognostic or diagnostic value, and eventually new drug targets. Keywords: neuroendocrine, neuroendocrine markers, gene expression profiling, cDNA microarray
2008-12-18 | GSE4328 | GEO
Project description:In this case report, we describe a 40-year-old patient with a large grade 2 pancreatic neuroendocrine tumour (pNET) with spleen metastasis. Albeit radical resection, he developed liver metastasis after 2 years, for which he underwent radio frequency ablation and embolization, and was treated successfully with different subsequent lines of systemic therapy. Eight years after the initial diagnosis, he was admitted for symptomatic and refractory hypercalcaemia, due to calcitriol synthesis by the liver metastasis. After tumour load reduction by hemihepatectomy, there was an initial normalization of hypercalcaemia, until it recurred after 18 months. In this period, the liver metastasis had progressed despite chemo- and immunotherapy. Patient underwent an additional extend hemihepatectomy, from which he recovered well with normalization of calcium levels. This case illustrates the hormonal plasticity of pNETs and shows how prolonged survival can be achieved for metastatic pNET by multimodality approach.
| S-EPMC6900336 | biostudies-literature
Project description:Devil facial tumour (DFT) disease, a transmissible cancer where the infectious agent is the tumour itself, has caused a dramatic decrease in Tasmanian devil numbers in the wild. The purpose of this study was to take a candidate gene/pathway approach to identify potentially perturbed genes or pathways in DFT. A fusion of chromosome 1 and X is posited as the initial event leading to the development of DFT, with the rearranged chromosome 1 material now stably maintained as the tumour spreads through the population. This hypothesis makes chromosome 1 a prime chromosome on which to search for mutations involved in tumourigenesis. As DFT1 has a Schwann cell origin, we selected genes commonly implicated in tumour pathways in human nerve cancers, or cancers more generally, to determine whether they were rearranged in DFT1, and mapped them using molecular cytogenetics. Many cancer-related genes were rearranged, such as the region containing the tumour suppressor NF2 and a copy gain for ERBB3, a member of the epidermal growth factor receptor family of receptor tyrosine kinases implicated in proliferation and invasion of tumours in humans. Our mapping results have provided strong candidates not previously detected by sequencing DFT1 genomes.
| S-EPMC5562891 | biostudies-literature
Project description:Background: Therapy-related neuroendocrine prostate cancer (NEPC) is a lethal castration-resistant prostate cancer (CRPC) subtype that, at present, lacks well-characterized molecular biomarkers. The clinical diagnosis of this disease is dependent on biopsy and histological assessment: methods that are experience-based and easily misdiagnosed due to tumor heterogeneity. The development of robust diagnostic tools for NEPC may assist clinicians in making medical decisions on the choice of continuing anti-androgen receptor therapy or switching to platinum-based chemotherapy. Methods: Gene expression profiles and clinical characteristics data of 208 samples of metastatic CRPC, including castration-resistant prostate adenocarcinoma (CRPC-adeno) and castration-resistant neuroendocrine prostate adenocarcinoma (CRPC-NE), were obtained from the prad_su2c_2019 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was subsequently used to construct a free-scale gene co-expression network to study the interrelationship between the potential modules and clinical features of metastatic prostate adenocarcinoma and to identify hub genes in the modules. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to build a model to predict the clinical characteristics of CRPC-NE. The findings were then verified in the nepc_wcm_2016 dataset. Results: A total of 51 co-expression modules were successfully constructed using WGCNA, of which three co-expression modules were found to be significantly associated with the neuroendocrine features and the NEPC score. In total, four novel genes, including NPTX1, PCSK1, ASXL3, and TRIM9, were all significantly upregulated in NEPC compared with the adenocarcinoma samples, and these genes were all associated with the neuroactive ligand receptor interaction pathway. Next, the expression levels of these four genes were used to construct an NEPC diagnosis model, which was successfully able to distinguish CRPC-NE from CRPC-adeno samples in both the training and the validation cohorts. Moreover, the values of the area under the receiver operating characteristic (AUC) were 0.995 and 0.833 for the training and validation cohorts, respectively. Conclusion: The present study identified four specific novel biomarkers for therapy-related NEPC, and these biomarkers may serve as an effective tool for the diagnosis of NEPC, thereby meriting further study.
| S-EPMC8503838 | biostudies-literature