scholarly journals Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2054
Author(s):  
Michele Simbolo ◽  
Mirna Bilotta ◽  
Andrea Mafficini ◽  
Claudio Luchini ◽  
Daniela Furlan ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Expression Profiling ◽  
Mutational Analysis ◽  
Expression Profiles ◽  
Tumor Grade ◽  
Proliferation Index ◽  
Specific Expression ◽  
Major Predictor ◽  
Data Call

Pancreatic neuroendocrine tumors (PanNETs) display variable aggressive behavior. A major predictor of survival is tumor grade based on the Ki67 proliferation index. As information on transcriptomic profiles of PanNETs with different tumor grades is limited, we investigated 29 PanNETs (17 G1, 7 G2, 5 G3) for their expression profiles, mutations in 16 PanNET relevant genes and LINE-1 DNA methylation profiles. A total of 3050 genes were differentially expressed between tumors with different grades (p < 0.05): 1279 in G3 vs. G2; 2757 in G3 vs. G1; and 203 in G2 vs. G1. Mutational analysis showed 57 alterations in 11 genes, the most frequent being MEN1 (18/29), DAXX (7/29), ATRX (6/29) and MUTYH (5/29). The presence and type of mutations did not correlate with the specific expression profiles associated with different grades. LINE-1 showed significantly lower methylation in G2/G3 versus G1 tumors (p = 0.007). The expression profiles of matched primaries and metastasis (nodal, hepatic and colorectal wall) of three cases confirmed the role of Ki67 in defining specific expression profiles, which clustered according to tumor grades, independently from anatomic location or patient of origin. Such data call for future exploration of the role of Ki67 in tumor progression, given its involvement in chromosomal stability.

scholarly journals TET2/IDH1/2/WT1 and NPM1 Mutations Influence the RUNX1 Expression Correlations in Acute Myeloid Leukemia

Medicina ◽  
2020 ◽  
Vol 56 (12) ◽  
pp. 637
Author(s):  
Sergiu Pasca ◽  
Ancuta Jurj ◽  
Ciprian Tomuleasa ◽  
Mihnea Zdrenghea
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mutational Analysis ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Runx1 Expression ◽  
Acute Myeloid

Background and objectives: Mutational analysis has led to a better understanding of acute myeloid leukemia (AML) biology and to an improvement in clinical management. Some of the most important mutations that affect AML biology are represented by mutations in genes related to methylation, more specifically: TET2, IDH1, IDH2 and WT1. Because it has been shown in numerous studies that mutations in these genes lead to similar expression profiles and phenotypes in AML, we decided to assess if mutations in any of those genes interact with other genes important for AML. Materials and Methods: We downloaded the clinical data, mutational profile and expression profile from the TCGA LAML dataset via cBioPortal. Data were analyzed using classical statistical methods and functional enrichment analysis software represented by STRING and GOrilla. Results: The first step we took was to assess the 196 AML cases that had a mutational profile available and observe the mutations that overlapped with TET2/IDH1/2/WT1 mutations. We observed that RUNX1 mutations significantly overlap with TET2/IDH1/2/WT1 mutations. Because of this, we decided to further investigate the role of RUNX1 mutations in modulating the level of RUNX1 mRNA and observed that RUNX1 mutant cases presented higher levels of RUNX1 mRNA. Because there were only 16 cases of RUNX1 mutant samples and that mutations in this gene determined a change in mRNA expression, we further observed the correlation between RUNX1 and other mRNAs in subgroups regarding the presence of hypermethylating mutations and NPM1. Here, we observed that both TET2/IDH1/2/WT1 and NPM1 mutations increase the number of genes negatively correlated with RUNX1 and that these genes were significantly linked to myeloid activation. Conclusions: In the current study, we have shown that NPM1 and TET2/IDH1/2/WT1 mutations increase the number of negative correlations of RUNX1 with other transcripts involved in myeloid differentiation.

MicroRNA Expression Profiles in Acute Myeloid Leukemia with Common Translocations.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3181-3181
Author(s):  
Zejuan Li ◽  
Jun Lu ◽  
Miao Sun ◽  
Shuangli Mi ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Expression Profiling ◽  
Myeloid Leukemia ◽  
Target Genes ◽  
Expression Profiles ◽  
Genetic Alterations ◽  
In Vivo Models ◽  
Normal Controls ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. It is estimated that 13,410 cases will be diagnosed and 8,990 will die of AML in the United States in 2007 (http://seer.cancer.gov). AML is a genetically diverse hematopoietic malignancy with variable response to treatment. Expression profiling of protein-coding genes using DNA microarray in AML has resulted in inconsistent data from different laboratories. Therefore, further validation of these observations in large cohorts and in independent studies is definitely required before clinical application becomes feasible. Recently, Golub and colleagues described a new, bead-based flow cytometric microRNA (miRNAs, miRs) expression profiling method that could successfully classify tumors. MiRNAs are endogenous ∼22 nucleotide non-coding RNAs, which can function as oncogenes and tumor suppressors. To provide new insights into the complex genetic alterations in leukemogenesis and to identify novel markers for diagnosis and treatment of AML, we performed a genome-wide analysis of miRNA expression profiles using the bead-based method on 54 AML samples with common translocations including t(15;17), t(8;21), inv(16), and 11q23 rearrangement, along with normal controls. In both unsupervised and supervised hierarchical cluster analyses, we observed that t(15;17) samples grouped together as one cluster, as do the 11q23 rearrangement samples. Interestingly, t(8;21) and inv(16), both CBF (core-binding factor) AMLs, grouped together as a unique cluster. Forty-one miRNAs exhibited significantly differential expression between different subtypes of AMLs, and/or between AMLs and normal controls. Notably, expression signature of a minimal number of two, three, and seven miRNAs could be used for class prediction of CBF, t(15;17), and 11q23 rearrangement AMLs, respectively, with an overall diagnostic accuracy of 94–96%. We further showed that overexpression of the two discriminatory miRNAs in CBF AML is associated with epigenetic regulation, rather than DNA copy number amplification. Moreover, several important target genes of these discriminatory miRNAs have also been validated. We are currently exploring the role of these discriminatory miRNAs and their critical target genes in the development of AML using in vitro and in vivo models. This work will enhance our understanding of the biological role of these miRNAs and their targets in leukemogenesis.

Long Noncoding RNA Expression Profiling By Microarray in Diffuse Large B-Cell Lymphoma and Preliminary Bioinformatics Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5286-5286
Author(s):  
Honghui Huang ◽  
Fei Xiao ◽  
Lijing Shen ◽  
Xiaofeng Han ◽  
Fangyuan Chen ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Profiling ◽  
Kegg Pathway ◽  
Expression Profiles ◽  
B Cell Lymphoma ◽  
Differentially Expressed ◽  
Newly Diagnosed ◽  
Disease States ◽  
Mrna Expression Profiling

Abstract Objective: Application of high-throughput genomics technology to analysis the differences in lncRNA/mRNA expression profiles between the patients with diffuse large B cell lymphoma (DLBCL) and reactive hyperplasia of lymph node (RLN), and between different disease states of DLBCL, in order to explore the role of the aberrantly expressed lncRNAs in the pathogenesis of DLBCL. Materials and methods: Tumor tissue samples from five newly diagnosed DLBCL, 3 relapsed DLBCL patients and 4 samples of RLN were collected. Agilent Human lncRNA/mRNA Microarray (4×180K) was used to profile differentially expression of lncRNA/mRNAs. Bioinformatics methods were performed for data analysis, including screening of differentially expressed lncRNA/mRNAs, gene ontology (GO) and KEGG pathway enrichment analysis, and lncRNA/mRNA co-expression network construction. Portion of dysregulated lncRNAs from the microarray data analysis was selected for validation using quantitative real-time polymerase chain reaction (qRT-PCR). Results: (1) In patients with newly diagnosed DLBCL, compared to RLN, a total of 5,806 dysregulated lncRNAs were identified (P<0.05, FC≥2-fold). Among these, 2,650 lncRNAs were significantly upregulated, while 3,156 lncRNAs were significantly downregulated. From the mRNA expression profiling data, 5,628 differently expressed mRNAs were found (P<0.05, FC≥2-fold). Among them, 2,045 were significantly upregulated and 3,583 downregulated. The most enriched GO term and KEGG pathway annotation associated with DLBCL was cell cycle regulation. The coding and non-coding gene expression network construction showed the significantly correlation between lnc-FAM27B-22:1 and mRNAs, including CDCA7L, CEBPB, CHRDL1 and SMIM9. We speculated that lnc-FAM27B-22:1 might have a critical function in pathogenesis of DLBCL. (2) In patients with primary refractory DLBCL, compared with chemo-sensitive patients, a total of 425 dysregulated lncRNAs were identified(P<0.05, FC≥2-fold). Among these, 124 lncRNAs were significantly upregulated, while 301 lncRNAs were significantly downregulated. From the mRNA expression profiling data, 251 differently expressed mRNAs were found(P<0.05, FC≥2-fold). Among them, 90 were significantly upregulated and 106 downregulated. The most enriched GO terms targeted by dysregulated transcripts were involved in a variety of functions. KEGG pathway analysis showed that 25 pathways corresponded to dysregulated transcripts and the most enriched networks correlated with tumor were Wnt and P53 signaling pathway. (3) In patients with relapsed DLBCL, compared with newly diagnosed patients, a total of 605 dysregulated lncRNAs were identified(P<0.05, FC≥2-fold). Among these, 169 lncRNAs were significantly upregulated, while 436 lncRNAs were significantly downregulated. From the mRNA expression profiling data, 365 differently expressed mRNAs were found(P<0.05, FC≥2-fold). Among them, 201 were significantly upregulated and 164 downregulated. The most enriched GO terms targeted by dysregulated transcripts were involved in a variety of functions. KEGG pathway analysis showed that 24 pathways corresponded to dysregulated transcripts and the most enriched network correlated with tumor was JAK-STAT signaling pathway. (4) Fourteen dysregulated lncRNAs expressions were analyzed in the same sample series using qRT-PCR to validate the microarray analysis results. In all but one lncRNA, consistent trend of expression changes was observed in two methods. Conclusions: In patients with newly diagnosed DLBCL versus RLN, and between different disease states of DLBCL, the lncRNA/mRNA expression profiles were significantly altered. Differentially expressed mRNAs are involved in a number of biological functions and signaling pathways. It prompt lncRNA may play an important role in the mechanism of occurrence, drug resistance and relapse of DLBCL. The above results provide the theory basis for the further study on the role of differentially expressed lncRNA in the development of DLBCL and its potential application as the possible biomarkers of early diagnosis and prognosis. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Drosophila Forkhead/Fox transcription factor Jumeau mediates specific cardiac progenitor cell divisions by regulating expression of the kinesin Nebbish

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew J. Kump ◽  
Manoj Panta ◽  
Kristopher R. Schwab ◽  
Mark H. Inlow ◽  
Shaad M. Ahmad
Keyword(s):  
Cell Division ◽  
Progenitor Cell ◽  
Expression Profiles ◽  
Loss Of Function ◽  
Phenotypic Analysis ◽  
Specific Expression ◽  
Cardiac Progenitor Cell ◽  
Cell Divisions ◽  
Downstream Effectors

AbstractForkhead (Fkh/Fox) domain transcription factors (TFs) mediate multiple cardiogenic processes in both mammals and Drosophila. We showed previously that the Drosophila Fox gene jumeau (jumu) controls three categories of cardiac progenitor cell division—asymmetric, symmetric, and cell division at an earlier stage—by regulating Polo kinase activity, and mediates the latter two categories in concert with the TF Myb. Those observations raised the question of whether other jumu-regulated genes also mediate all three categories of cardiac progenitor cell division or a subset thereof. By comparing microarray-based expression profiles of wild-type and jumu loss-of-function mesodermal cells, we identified nebbish (neb), a kinesin-encoding gene activated by jumu. Phenotypic analysis shows that neb is required for only two categories of jumu-regulated cardiac progenitor cell division: symmetric and cell division at an earlier stage. Synergistic genetic interactions between neb, jumu, Myb, and polo and the rescue of jumu mutations by ectopic cardiac mesoderm-specific expression of neb demonstrate that neb is an integral component of a jumu-regulated subnetwork mediating cardiac progenitor cell divisions. Our results emphasize the central role of Fox TFs in cardiogenesis and illustrate how a single TF can utilize different combinations of other regulators and downstream effectors to control distinct developmental processes.

scholarly journals Pearl Sac Gene Expression Profiles Associated With Pearl Attributes in the Silver-Lip Pearl Oyster, Pinctada maxima

2021 ◽  
Vol 11 ◽  
Author(s):  
Carmel McDougall ◽  
Felipe Aguilera ◽  
Ali Shokoohmand ◽  
Patrick Moase ◽  
Bernard M. Degnan
Keyword(s):  
Gene Expression ◽  
Expression Profiling ◽  
Structural Characteristics ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Pearl Oyster ◽  
Pearl Sac ◽  
Pinctada Maxima ◽  
Microtubule Function

Pearls are highly prized biomineralized gemstones produced by molluscs. The appearance and mineralogy of cultured pearls can vary markedly, greatly affecting their commercial value. To begin to understand the role of pearl sacs—organs that form in host oysters from explanted mantle tissues that surround and synthesize pearls—we undertook transcriptomic analyses to identify genes that are differentially expressed in sacs producing pearls with different surface and structural characteristics. Our results indicate that gene expression profiles correlate with different pearl defects, suggesting that gene regulation in the pearl sac contributes to pearl appearance and quality. For instance, pearl sacs that produced pearls with surface non-lustrous calcification significantly down-regulate genes associated with cilia and microtubule function compared to pearl sacs giving rise to lustrous pearls. These results suggest that gene expression profiling can advance our understanding of processes that control biomineralization, which may be of direct value to the pearl industry, particularly in relation to defects that result in low value pearls.

scholarly journals Differential expression of circulating exosomal microRNAs in refractory intracranial atherosclerosis associated with antiangiogenesis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hao Jiang ◽  
Juan F. Toscano ◽  
Shlee S. Song ◽  
Konrad H. Schlick ◽  
Oana M. Dumitrascu ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Biological Functions ◽  
Specific Expression ◽  
Blood Samples ◽  
Intracranial Atherosclerotic Disease ◽  
Antiangiogenic Factors ◽  
Ischemic Events ◽  
Generation Sequencing

AbstractIntracranial atherosclerotic disease (ICAD) is a common cause of stroke with high rates of ischemic recurrence. We aimed to investigate the role of circulating exosomal microRNAs (e-miRNAs) in recurrent ischemic events in ICAD. Consecutive patients with severe ICAD undergoing intensive medical management (IMM) were prospectively enrolled. Those with recurrent ischemic events despite IMM during 6-month follow up were algorithmically matched to IMM responders. Baseline blood e-miRNA expression levels of the matched patients were measured using next generation sequencing. A total of 122 e-miRNAs were isolated from blood samples of 10 non-responders and 11 responders. Thirteen e-miRNAs predicted IMM failure with 90% sensitivity and 100% specificity. Ingenuity pathway analysis (IPA) determined 10 of the 13 e-miRNAs were significantly associated with angiogenesis-related biological functions (p < 0.025) and angiogenic factors that have been associated with recurrent ischemic events in ICAD. These e-miRNAs included miR-122-5p, miR-192-5p, miR-27b-3p, miR-16-5p, miR-486-5p, miR-30c-5p, miR-10b-5p, miR-10a-5p, miR-101-3p, and miR-24-3p. As predicted by IPA, the specific expression profiles of these 10 e-miRNAs in non-responders had a net result of inhibition of the angiogenesis-related functions and up expression of the antiangiogenic factors. This study revealed distinct expression profiles of circulating e-miRNAs in refractory ICAD, suggesting an antiangiogenic mechanism underlying IMM failure.

Sign in / Sign up

Export Citation Format

Share Document