Project description:Small intestinal neuroendocrine tumors (SI-NETs) arise from serotonin-producing enterochromaffin cells. SI-NETs are often well-differentiated tumors and most patients have regional or distant metastases at initial presentation. MicroRNAs (miRs) are post-transcriptional regulators which are important in diverse biological processes and can function as tumor suppressor genes or oncogenes. This study aims to identify an exclusive SI-NETs miR profile that may have a critical role in development, diagnosis, prognosis and progression of these malignancies.
Project description:Small intestine neuroendocrine tumors are the commonest neuroendocrine tumors of the GI tract. Next gen sequencing of the whole exome was undertaken to identify SNPs and SCNA in these tumor samples. Subsequent bioinformatic anlaysis was done where the reads ratios of tumor/normal were log2 tranformed, segments indentified with DNAcopy (R package) and regions of SCNA were identified. Amplification of chr 4, 5, 14 and 20 was observed. The validation of these SCNAs was done with arrayCGH. The results of array CGH is in concordeance with the exome sequencing data. DNA from matched tumor and normal sample of SI-NETs was done by spin column method. Libraries were constructed and exome enriched for next gen sequencing. The same gDNA was hybridized with Cy5 and Cy3 and subsequent analysis was done. This study represents the CGH portion of the study.
Project description:Small intestine neuroendocrine tumors are the commonest neuroendocrine tumors of the GI tract. Next gen sequencing of the whole exome was undertaken to identify SNPs and SCNA in these tumor samples. Subsequent bioinformatic anlaysis was done where the reads ratios of tumor/normal were log2 tranformed, segments indentified with DNAcopy (R package) and regions of SCNA were identified. Amplification of chr 4, 5, 14 and 20 was observed. The validation of these SCNAs was done with arrayCGH. The results of array CGH is in concordeance with the exome sequencing data.
Project description:Small intestinal neuroendocrine tumors (SI-NETs) arise from serotonin-producing enterochromaffin cells. SI-NETs are often well-differentiated tumors and most patients have regional or distant metastases at initial presentation. MicroRNAs (miRs) are post-transcriptional regulators which are important in diverse biological processes and can function as tumor suppressor genes or oncogenes. This study aims to identify an exclusive SI-NETs miR profile that may have a critical role in development, diagnosis, prognosis and progression of these malignancies.
Project description:Although there has been increased knowledge about the molecular biology of neuroendocrine tumors (NETs), little is known about thymic carcinoids and even less about those with excessive hormone disorders, such as ectopic ACTH syndrome. This study was designed to gain insights into molecular networks underlying the tumorigenesis of thymic carcinoids with ACTH secretion. By an approach integrating cDNA microarray and methods of computational biology, we compare gene expression profile between ACTH-producing thymic carcinoids and normal thymus. Totally there are 63 biological categories increased and 108 decreased in thymic carcinoids. Cell proliferation was stimulated which may explain the relatively uncontrolled cell growth of the tumor. Dysregulation of Notch signaling pathway was likely underlying the neuroendocrine features of this type of tumors. Moreover, the inhibition of the immunity and the increased neuropeptide signaling molecules, POMC and its sorting molecule CPE, made the clinical manifestation reasonable and thus validated the array data. In conclusion, thymic carcinoids have distinguished gene expression pattern from the normal thymus and they are characterized by deregulations of a series of biofunctions, which may be involved in the development of neuroendocrine tumor. This study hence has provided not only a detailed comprehension of the molecular pathogenesis of thymic carcinoid with ectopic ACTH syndrome, but also a road map to approach thymic neuroendocrine tumors at the system level. Transcriptome profilings were performed to identify differentially expressed cDNAs between five samples (NCs) from thymic tumor-suffering patients with ectopic ACTH syndrome (i.e., NC1, NC2, NC3, NC4, NC5, NC6) and six samples (ACs) of the noncancerous thymuses (i.e., AC1, AC2, AC3, AC4, AC5).
Project description:Assessment of mesenteric fibrosis (MF) presence and severity in small-intestinal neuroendocrine tumors (SI-NETs) remains a diagnostic challenge. To explore possible biomarkers for MF presence, a proteomic analysis was performed of the tumor and stroma compartment of primary SI-NETs and paired mesenteric metastasis.
Project description:Small intestinal neuroendocrine tumors (SI-NETs) arise from serotonin-producing enterochromaffin cells. SI-NETs are often well-differentiated tumors and most patients have regional or distant metastases at initial presentation. MicroRNAs (miRs) are post-transcriptional regulators which are important in diverse biological processes and can function as tumor suppressor genes or oncogenes. This study aims to identify an exclusive SI-NETs miR profile that may have a critical role in development, diagnosis, prognosis and progression of these malignancies. Five human NET cell lines, one octreotide-treated CNDT2.5 cells, one microdissected normal enterochromaffin cells, three snap-frozen normal ileum specimens and 15 SI-NET specimens at different stage of malignancy, five primary tumors, five mesentery metastases and five liver metastases, were included in this study. Total RNA was hybridized onto Affymetrix GeneChipM-BM-. miR arrays for genome-wide profiling. Array data summarization, normalization, and quality control were performed using miRNA QC Tool software.
Project description:Pancreatic Neuroendocrine tumors are challenging to diagnose and often detected at advanced stages due to lack of specific and sensitive biomarkers. This study utilized proteomics as a valuable approach for cancer biomarker discovery, therefore, mass spectrometry-based proteomic profiling was conducted on plasma samples from 12 subjects (3 controls; 9 PanNET patients) to identify potential proteins capable of effectively distinguish PanNET from healthy controls. 13.2% of proteins were uniquely identified in PanNET, while 60% were commonly expressed in PanNET and controls. 17 proteins exhibiting significant differential expression between PanNET and controls were identified with downstream analysis.