Characterizing the heterogeneity in 5-aminolevulinic acid–induced fluorescence in glioblastoma

OBJECTIVE5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence is an effective surgical adjunct for the intraoperative identification of tumor tissue during resection of high-grade gliomas. The use of 5-ALA-induced PpIX fluorescence in glioblastoma (GBM) has been shown to double the extent of gross-total resection and 6-month progression-free survival. The heterogeneity of 5-ALA-induced PpIX fluorescence observed during surgery presents a technical and diagnostic challenge when utilizing this tool intraoperatively. While some regions show bright fluorescence after 5-ALA administration, other regions do not, despite that both regions of the tumor may be histopathologically indistinguishable. The authors examined the biological basis of this heterogeneity using computational methods.METHODSThe authors collected both fluorescent and nonfluorescent GBM specimens from a total of 14 patients undergoing surgery and examined their gene expression profiles.RESULTSIn this study, the authors found that the gene expression patterns characterizing fluorescent and nonfluorescent GBM surgical specimens were profoundly different and were associated with distinct cellular functions and different biological pathways. Nonfluorescent tumor tissue tended to resemble the neural subtype of GBM; meanwhile, fluorescent tumor tissue did not exhibit a prominent pattern corresponding to known subtypes of GBM. Consistent with this observation, neural GBM samples from The Cancer Genome Atlas database exhibited a significantly lower fluorescence score than nonneural GBM samples as determined by a fluorescence gene signature developed by the authors.CONCLUSIONSThese results provide a greater understanding regarding the biological basis of differential fluorescence observed intraoperatively and can provide a basis to identify novel strategies to maximize the effectiveness of fluorescence agents.

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The Association between TIF1 Family Members and Cancer Stemness in Solid Tumors

Cancers ◽

10.3390/cancers13071528 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1528

Author(s):

Patrycja Czerwinska ◽

Nikola Agata Wlodarczyk ◽

Anna Maria Jaworska ◽

Andrzej Adam Mackiewicz

Keyword(s):

Gene Expression ◽

Stem Cell ◽

Solid Tumors ◽

Cancer Progression ◽

Expression Profiles ◽

Expression Patterns ◽

Family Members ◽

The Cancer Genome Atlas ◽

Tumor Type ◽

Cancer Stemness

Cancer progression entails a gradual loss of a differentiated phenotype in parallel with the acquisition of stem cell-like features. Cancer de-differentiation and the acquisition of stemness features are mediated by the transcriptional and epigenetic dysregulation of cancer cells. Here, using publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and harnessing several bioinformatic tools, we characterized the association between Transcriptional Intermediary Factor 1 (TIF1) family members and cancer stemness in 27 distinct types of solid tumors. We aimed to define the prognostic value for TIF1 members in predicting a stem cell-like cancer phenotype and patient outcome. Our results demonstrate that high expression of only one member of the TIF1 family, namely TIF1β (also known as Tripartite Motif protein 28, TRIM28) is consequently associated with enriched cancer stemness across the tested solid tumor types, resulting in a worse prognosis for cancer patients. TRIM28 is highly expressed in higher grade tumors that exhibit stem cell-like traits. In contrast to other TIF1 members, only TIF1β/TRIM28-associated gene expression profiles were robustly enriched with stemness markers regardless of the tumor type. Our work demonstrates that TIF1 family members exhibit distinct expression patterns in stem cell-like tumors, despite their structural and functional similarity. Among other TIF1 members, only TRIM28 might serve as a marker of cancer stemness features.

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Extracting a Biologically Relevant Latent Space from Cancer Transcriptomes with Variational Autoencoders

10.1101/174474 ◽

2017 ◽

Cited By ~ 14

Author(s):

Gregory P. Way ◽

Casey S. Greene

Keyword(s):

Neural Network ◽

Gene Expression ◽

Deep Neural Network ◽

Expression Profiles ◽

Expression Patterns ◽

The Cancer Genome Atlas ◽

Neural Network Models ◽

Neural Network Approach ◽

Biologically Relevant ◽

Latent Space

The Cancer Genome Atlas (TCGA) has profiled over 10,000 tumors across 33 different cancer-types for many genomic features, including gene expression levels. Gene expression measurements capture substantial information about the state of each tumor. Certain classes of deep neural network models are capable of learning a meaningful latent space. Such a latent space could be used to explore and generate hypothetical gene expression profiles under various types of molecular and genetic perturbation. For example, one might wish to use such a model to predict a tumor’s response to specific therapies or to characterize complex gene expression activations existing in differential proportions in different tumors. Variational autoencoders (VAEs) are a deep neural network approach capable of generating meaningful latent spaces for image and text data. In this work, we sought to determine the extent to which a VAE can be trained to model cancer gene expression, and whether or not such a VAE would capture biologically-relevant features. In the following report, we introduce a VAE trained on TCGA pan-cancer RNA-seq data, identify specific patterns in the VAE encoded features, and discuss potential merits of the approach. We name our method “Tybalt” after an instigative, cat-like character who sets a cascading chain of events in motion in Shakespeare’s “Romeo and Juliet”. From a systems biology perspective, Tybalt could one day aid in cancer stratification or predict specific activated expression patterns that would result from genetic changes or treatment effects.

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Hub Gene Identification and Prognostic Model Establishment for Patients with HBV-related Hepatocellular Carcinoma

10.21203/rs.3.rs-269454/v1 ◽

2021 ◽

Author(s):

Lianmei Wang ◽

Jing Liu ◽

Zhong Xian ◽

Jingzhuo Tian ◽

Chunying Li ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Prognostic Model ◽

Expression Profiles ◽

Expression Patterns ◽

Cyclin B1 ◽

Mitotic Checkpoint ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Hub Genes

Abstract Hepatocellular carcinoma (HCC) is associated with poor 5-year survival. Chronic infection with hepatitis B virus (HBV) contributes to ~ 50% of HCC cases. Establishment of a prognostic model is pivotal for clinical therapy of HBV-related HCC (HBV–HCC). We downloaded gene-expression profiles from Gene expression omnibus (GEO) datasets with HBV-HCC patients and the corresponding controls. Integration of these differentially expressed genes (DEGs) was achieved with the Robustrankaggreg (RRA) method. DEGs functional analyses and pathway analyses was performed using the Gene ontology (GO) database, and the Kyoto encyclopedia of genes and genomes (KEGG) database respectively. DNA topoisomerase II alpha (TOP2A), Disks large-associated protein 5 (DLGAP5), RAD51 associated protein 1 (RAD51AP1), ZW10 interactor (ZWINT), BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B), Cyclin B1 (CCNB1), Forkhead box M1 (FOXM1), Cyclin B2 (CCNB2), Aurora kinase A (AURKA), and Cyclin-dependent kinase 1 (CDK1) were identified as the top-ten hub genes. These hub-genes were verified by the Liver cancer-riken, JP project from international cancer genome consortium (ICGC-LIRI-JP) project, The Cancer genome atlas (TCGA) HCC cohort, and Human protein profiles dataset. FOXM1 and CDK1 were found to be prognostic-related molecules for HBV-HCC patients. The expression patterns of FOXM1 and CDK1were consistently in human and mouse. Furthermore, a nomogram model based on histology grade, pathology stage, sex and, expression of FOXM1 and CDK1 was built to predict the prognosis for HBV–HCC patients. The nomogram model could be used to predict the prognosis of HBV-HCC cases.

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Screening of gene markers related to the prognosis of metastatic skin cutaneous melanoma based on Logit regression and survival analysis

BMC Medical Genomics ◽

10.1186/s12920-021-00923-0 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Guoliang Jia ◽

Zheyu Song ◽

Zhonghang Xu ◽

Youmao Tao ◽

Yuanyu Wu ◽

...

Keyword(s):

Gene Expression ◽

Cutaneous Melanoma ◽

Expression Profiles ◽

The Cancer Genome Atlas ◽

Training Dataset ◽

Validation Dataset ◽

Survival Prognosis ◽

Gene Markers ◽

Clinical Prognosis ◽

Logit Regression

Abstract Background Bioinformatics was used to analyze the skin cutaneous melanoma (SKCM) gene expression profile to provide a theoretical basis for further studying the mechanism underlying metastatic SKCM and the clinical prognosis. Methods We downloaded the gene expression profiles of 358 metastatic and 102 primary (nonmetastatic) CM samples from The Cancer Genome Atlas (TCGA) database as a training dataset and the GSE65904 dataset from the National Center for Biotechnology Information database as a validation dataset. Differentially expressed genes (DEGs) were screened using the limma package of R3.4.1, and prognosis-related feature DEGs were screened using Logit regression (LR) and survival analyses. We also used the STRING online database, Cytoscape software, and Database for Annotation, Visualization and Integrated Discovery software for protein–protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses based on the screened DEGs. Results Of the 876 DEGs selected, 11 (ZNF750, NLRP6, TGM3, KRTDAP, CAMSAP3, KRT6C, CALML5, SPRR2E, CD3G, RTP5, and FAM83C) were screened using LR analysis. The survival prognosis of nonmetastatic group was better compared to the metastatic group between the TCGA training and validation datasets. The 11 DEGs were involved in 9 KEGG signaling pathways, and of these 11 DEGs, CALML5 was a feature DEG involved in the melanogenesis pathway, 12 targets of which were collected. Conclusion The feature DEGs screened, such as CALML5, are related to the prognosis of metastatic CM according to LR. Our results provide new ideas for exploring the molecular mechanism underlying CM metastasis and finding new diagnostic prognostic markers.

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Comprehensive Comparison of Amnion Stromal Cells and Chorion Stromal Cells by RNA-Seq

International Journal of Molecular Sciences ◽

10.3390/ijms22041901 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1901

Author(s):

Brielle Jones ◽

Chaoyang Li ◽

Min Sung Park ◽

Anne Lerch ◽

Vimal Jacob ◽

...

Keyword(s):

Gene Expression ◽

Stromal Cells ◽

Expression Profiles ◽

Expression Patterns ◽

Principal Component ◽

Differentially Expressed ◽

Inflammatory Factor ◽

Next Generation Sequencing Technology ◽

Angiogenic Potential ◽

Anti Inflammatory

Mesenchymal stromal cells derived from the fetal placenta, composed of an amnion membrane, chorion membrane, and umbilical cord, have emerged as promising sources for regenerative medicine. Here, we used next-generation sequencing technology to comprehensively compare amniotic stromal cells (ASCs) with chorionic stromal cells (CSCs) at the molecular and signaling levels. Principal component analysis showed a clear dichotomy of gene expression profiles between ASCs and CSCs. Unsupervised hierarchical clustering confirmed that the biological repeats of ASCs and CSCs were able to respectively group together. Supervised analysis identified differentially expressed genes, such as LMO3, HOXA11, and HOXA13, and differentially expressed isoforms, such as CXCL6 and HGF. Gene Ontology (GO) analysis showed that the GO terms of the extracellular matrix, angiogenesis, and cell adhesion were significantly enriched in CSCs. We further explored the factors associated with inflammation and angiogenesis using a multiplex assay. In comparison with ASCs, CSCs secreted higher levels of angiogenic factors, including angiogenin, VEGFA, HGF, and bFGF. The results of a tube formation assay proved that CSCs exhibited a strong angiogenic function. However, ASCs secreted two-fold more of an anti-inflammatory factor, TSG-6, than CSCs. In conclusion, our study demonstrated the differential gene expression patterns between ASCs and CSCs. CSCs have superior angiogenic potential, whereas ASCs exhibit increased anti-inflammatory properties.

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Discovering Distinct Patterns in Gene Expression Profiles

Journal of Integrative Bioinformatics ◽

10.1515/jib-2008-105 ◽

2008 ◽

Vol 5 (2) ◽

Cited By ~ 1

Author(s):

Li Teng ◽

Laiwan Chan

Keyword(s):

Gene Expression ◽

Large Scale ◽

Expression Profiles ◽

Expression Patterns ◽

Gene Expression Profiles ◽

Clustering Methods ◽

Gene Expressions ◽

Real Gene ◽

Large Scale Dataset ◽

Coexpressed Genes

SummaryTraditional analysis of gene expression profiles use clustering to find groups of coexpressed genes which have similar expression patterns. However clustering is time consuming and could be diffcult for very large scale dataset. We proposed the idea of Discovering Distinct Patterns (DDP) in gene expression profiles. Since patterns showing by the gene expressions reveal their regulate mechanisms. It is significant to find all different patterns existing in the dataset when there is little prior knowledge. It is also a helpful start before taking on further analysis. We propose an algorithm for DDP by iteratively picking out pairs of gene expression patterns which have the largest dissimilarities. This method can also be used as preprocessing to initialize centers for clustering methods, like K-means. Experiments on both synthetic dataset and real gene expression datasets show our method is very effective in finding distinct patterns which have gene functional significance and is also effcient.

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Comparison of gene expression in fresh and frozen–thawed human preimplantation embryos

Reproduction ◽

10.1530/rep-12-0047 ◽

2012 ◽

Vol 144 (5) ◽

pp. 569-582 ◽

Cited By ~ 31

Author(s):

Lisa Shaw ◽

Sharon F Sneddon ◽

Daniel R Brison ◽

Susan J Kimber

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Expression Patterns ◽

Developmental Expression ◽

Preimplantation Embryos ◽

Human Embryos ◽

Molecular Events ◽

Reliable Source ◽

Human Preimplantation Embryos ◽

Early Human

Identification and characterisation of differentially regulated genes in preimplantation human embryonic development are required to improve embryo quality and pregnancy rates in IVF. In this study, we examined expression of a number of genes known to be critical for early development and compared expression profiles in individual preimplantation human embryos to establish any differences in gene expression in fresh compared to frozen–thawed embryos used routinely in IVF. We analysed expression of 19 genes by cDNA amplification followed by quantitative real-time PCR in a panel of 44 fresh and frozen–thawed human preimplantation embryos. Fresh embryos were obtained from surplus early cleavage stage embryos and frozen–thawed embryos from cryopreserved 2PN embryos. Our aim was to determine differences in gene expression between fresh and frozen–thawed human embryos, but we also identified differences in developmental expression patterns for particular genes. We show that overall gene expression among embryos of the same stage is highly variable and our results indicate that expression levels between groups did differ and differences in expression of individual genes was detected. Our results show that gene expression from frozen–thawed embryos is more consistent when compared with fresh, suggesting that cryopreserved embryos may represent a reliable source for studying the molecular events underpinning early human embryo development.

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CFTR ΔF508 mutation has minimal effect on the gene expression profile of differentiated human airway epithelia

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00065.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. L545-L553 ◽

Cited By ~ 29

Author(s):

Joseph Zabner ◽

Todd E. Scheetz ◽

Hakeem G. Almabrazi ◽

Thomas L. Casavant ◽

Jian Huang ◽

...

Keyword(s):

Gene Expression ◽

Cystic Fibrosis ◽

Large Scale ◽

Expression Profiles ◽

Expression Patterns ◽

Primary Cultures ◽

Gene Expression Profiles ◽

Filter Method ◽

Tissue Destruction ◽

Airway Epithelia

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial chloride channel regulated by phosphorylation. Most of the disease-associated morbidity is the consequence of chronic lung infection with progressive tissue destruction. As an approach to investigate the cellular effects of CFTR mutations, we used large-scale microarray hybridization to contrast the gene expression profiles of well-differentiated primary cultures of human CF and non-CF airway epithelia grown under resting culture conditions. We surveyed the expression profiles for 10 non-CF and 10 ΔF508 homozygote samples. Of the 22,283 genes represented on the Affymetrix U133A GeneChip, we found evidence of significant changes in expression in 24 genes by two-sample t-test ( P < 0.00001). A second, three-filter method of comparative analysis found no significant differences between the groups. The levels of CFTR mRNA were comparable in both groups. There were no significant differences in the gene expression patterns between male and female CF specimens. There were 18 genes with significant increases and 6 genes with decreases in CF relative to non-CF samples. Although the function of many of the differentially expressed genes is unknown, one transcript that was elevated in CF, the KCl cotransporter (KCC4), is a candidate for further study. Overall, the results indicate that CFTR dysfunction has little direct impact on airway epithelial gene expression in samples grown under these conditions.

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Regional variations in ABC transporter expression along the mouse intestinal tract

Physiological Genomics ◽

10.1152/physiolgenomics.00150.2003 ◽

2004 ◽

Vol 17 (1) ◽

pp. 11-20 ◽

Cited By ~ 40

Author(s):

David M. Mutch ◽

Pascale Anderle ◽

Muriel Fiaux ◽

Robert Mansourian ◽

Karine Vidal ◽

...

Keyword(s):

Gene Expression ◽

Abc Transporter ◽

Expression Profile ◽

Abc Transporters ◽

Intestinal Tract ◽

Expression Profiles ◽

Expression Patterns ◽

Assessment Model ◽

Differentially Expressed ◽

Distal Intestine

The ATP-binding cassette (ABC) family of proteins comprise a group of membrane transporters involved in the transport of a wide variety of compounds, such as xenobiotics, vitamins, lipids, amino acids, and carbohydrates. Determining their regional expression patterns along the intestinal tract will further characterize their transport functions in the gut. The mRNA expression levels of murine ABC transporters in the duodenum, jejunum, ileum, and colon were examined using the Affymetrix MuU74v2 GeneChip set. Eight ABC transporters (Abcb2, Abcb3, Abcb9, Abcc3, Abcc6, Abcd1, Abcg5, and Abcg8) displayed significant differential gene expression along the intestinal tract, as determined by two statistical models (a global error assessment model and a classic ANOVA, both with a P < 0.01). Concordance with semiquantitative real-time PCR was high. Analyzing the promoters of the differentially expressed ABC transporters did not identify common transcriptional motifs between family members or with other genes; however, the expression profile for Abcb9 was highly correlated with fibulin-1, and both genes share a common complex promoter model involving the NFκB, zinc binding protein factor (ZBPF), GC-box factors SP1/GC (SP1F), and early growth response factor (EGRF) transcription binding motifs. The cellular location of another of the differentially expressed ABC transporters, Abcc3, was examined by immunohistochemistry. Staining revealed that the protein is consistently expressed in the basolateral compartment of enterocytes along the anterior-posterior axis of the intestine. Furthermore, the intensity of the staining pattern is concordant with the expression profile. This agrees with previous findings in which the mRNA, protein, and transport function of Abcc3 were increased in the rat distal intestine. These data reveal regional differences in gene expression profiles along the intestinal tract and demonstrate that a complete understanding of intestinal ABC transporter function can only be achieved by examining the physiologically distinct regions of the gut.

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Gene expression analysis of the pro-oestrous-stage rat uterus reveals neuroligin 2 as a novel steroid-regulated gene

Reproduction Fertility and Development ◽

10.1071/rd04040 ◽

2004 ◽

Vol 16 (8) ◽

pp. 763 ◽

Cited By ~ 8

Author(s):

Han-Seung Kang ◽

Chae-Kwan Lee ◽

Ju-Ran Kim ◽

Seong-Jin Yu ◽

Sung-Goo Kang ◽

...

Keyword(s):

Gene Expression ◽

Northern Blot ◽

Blot Analysis ◽

Northern Blot Analysis ◽

Expression Profiles ◽

Expression Patterns ◽

Oestrous Cycle ◽

Mrna Levels ◽

Rat Uterus ◽

Ovx Rats

In the present study, differential gene expression in the uteri of ovariectomised (OVX) and pro-oestrous rats (OVX v. pro-oestrus pair) was investigated using cDNA expression array analysis. Differential uterine gene expression in OVX rats and progesterone (P4)-injected OVX rats (OVX v. OVX + P4 pair) was also examined. The uterine gene expression profiles of these two sets of animals were also compared for the effects of P4 treatment. RNA samples were extracted from uterine tissues and reverse transcribed in the presence of [α32P]-dATP. Membrane sets of rat arrays were hybridised with cDNA probe sets. Northern blot analysis was used to validate the relative gene expression patterns obtained from the cDNA array. Of the 1176 cDNAs examined, 23 genes showed significant (>two-fold) changes in expression in the OVX v. pro-oestrus pair. Twenty of these genes were upregulated during pro-oestrus compared with their expression in the OVX rat uterus. In the OVX v. OVX + P4 pair, 22 genes showed significant (>two-fold) changes in gene expression. Twenty of these genes were upregulated in the OVX + P4 animals. The genes for nuclear factor I–XI, afadin, neuroligin 2, semaphorin Z, calpain 4, cyclase-associated protein homologue, thymosin β-4X and p8 were significantly upregulated in the uteri of the pro-oestrus and OVX + P4 rats of both experimental pairs compared with the OVX rat uteri. These genes appear to be under the control of P4. One of the most interesting findings of the present study is the unexpected and marked expression of the neuroligin 2 gene in the rat uterus. This gene is expressed at high levels in the central nervous system and acts as a nerve cell adhesion factor. According to Northern blot analysis, neuroligin 2 gene expression was higher during the pro-oestrus and metoestrus stages than during the oestrus and dioestrus stages of the oestrous cycle. In addition, neuroligin 2 mRNA levels were increased by both 17β-oestradiol (E2) and P4, although P4 administration upregulated gene expression to a greater extent than injection of E2. These results indicate that neuroligin 2 gene expression in the rat uterus is under the control of both E2 and P4, which are secreted periodically during the oestrous cycle.

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