Analysis of Individual Gene Expression Levels Indicates the Impact of Physiological Functions on Gene Expression Profiling Scores

2017 ◽  
Vol 36 (4) ◽  
pp. S396-S397
Author(s):  
S.A. Hall ◽  
S. Pinney ◽  
J. Sninsky ◽  
M. Machrus ◽  
R. Woodward ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Physiological Functions ◽  
Expression Levels ◽  
Individual Gene ◽  
The Impact ◽  
Gene Expression Levels

scholarly journals Impact of RNA degradation on measurements of gene expression

2014 ◽  
Author(s):  
Irene Gallego Romero ◽  
Athma A. Pai ◽  
Jenny Tung ◽  
Yoav Gilad
Keyword(s):  
Gene Expression ◽  
Expression Profiling ◽  
Rna Extraction ◽  
Rna Degradation ◽  
Significant Loss ◽  
Whole Genome ◽  
Expression Levels ◽  
Rna Quality ◽  
The Impact ◽  
Gene Expression Levels

The use of low quality RNA samples in whole-genome gene expression profiling remains controversial. It is unclear if transcript degradation in low quality RNA samples occurs uniformly, in which case the effects of degradation can be normalized, or whether different transcripts are degraded at different rates, potentially biasing measurements of expression levels. This concern has rendered the use of low quality RNA samples in whole-genome expression profiling problematic. Yet, low quality samples are at times the sole means of addressing specific questions – e.g., samples collected in the course of fieldwork. We sought to quantify the impact of variation in RNA quality on estimates of gene expression levels based on RNA-seq data. To do so, we collected expression data from tissue samples that were allowed to decay for varying amounts of time prior to RNA extraction. The RNA samples we collected spanned the entire range of RNA Integrity Number (RIN) values (a quality metric commonly used to assess RNA quality). We observed widespread effects of RNA quality on measurements of gene expression levels, as well as a slight but significant loss of library complexity in more degraded samples. While standard normalizations failed to account for the effects of degradation, we found that a simple linear model that controls for the effects of RIN can correct for the majority of these effects. We conclude that in instances where RIN and the effect of interest are not associated, this approach can help recover biologically meaningful signals in data from degraded RNA samples.

scholarly journals Gene expression profiling ofLeishmania (Leishmania) donovani: overcoming technical variation and exploiting biological variation

Parasitology ◽  
2007 ◽  
Vol 135 (2) ◽  
pp. 183-194 ◽  
Author(s):  
S. DECUYPERE ◽  
M. VANAERSCHOT ◽  
S. RIJAL ◽  
V. YARDLEY ◽  
L. MAES ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Molecular Characterization ◽  
Expression Profiling ◽  
Leishmania Donovani ◽  
Expression Levels ◽  
Intracellular Amastigotes ◽  
Gene Expression Levels

SUMMARYGene expression profiling is increasingly used in the field of infectious diseases for characterization of host, pathogen and the nature of their interaction. The purpose of this study was to develop a robust, standardized method for comparative expression profiling and molecular characterization ofLeishmania donovaniclinical isolates. The limitations and possibilities associated with expression profiling in intracellular amastigotes and promastigotes were assessed through a series of comparative experiments in which technical and biological parameters were scrutinized. On a technical level, our results show that it is essential to use parasite harvesting procedures that involve minimal disturbance of the parasite's environment in order to ‘freeze’ gene expression levels instantly; this is particularly a delicate task for intracellular amastigotes and for specific ‘sensory’ genes. On the biological level, we demonstrate that gene expression levels fluctuate duringin vitrodevelopment of both intracellular amastigotes and promastigotes. We chose to use expression-curves rather than single, specific, time-point measurements to capture this biological variation. Intracellular amastigote protocols need further refinement, but we describe a first generation tool for high-throughput comparative molecular characterization of patients' isolates, based on the changing expression profiles of promastigotes duringin vitrodifferentiation.

scholarly journals Codon usage is an important determinant of gene expression levels largely through its effects on transcription

2016 ◽  
Vol 113 (41) ◽  
pp. E6117-E6125 ◽  
Author(s):  
Zhipeng Zhou ◽  
Yunkun Dang ◽  
Mian Zhou ◽  
Lin Li ◽  
Chien-hung Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Codon Usage ◽  
Important Determinant ◽  
Mrna Translation ◽  
Mrna Levels ◽  
Protein Coding ◽  
Expression Levels ◽  
Highly Expressed Genes ◽  
The Impact ◽  
Gene Expression Levels

Codon usage biases are found in all eukaryotic and prokaryotic genomes, and preferred codons are more frequently used in highly expressed genes. The effects of codon usage on gene expression were previously thought to be mainly mediated by its impacts on translation. Here, we show that codon usage strongly correlates with both protein and mRNA levels genome-wide in the filamentous fungus Neurospora. Gene codon optimization also results in strong up-regulation of protein and RNA levels, suggesting that codon usage is an important determinant of gene expression. Surprisingly, we found that the impact of codon usage on gene expression results mainly from effects on transcription and is largely independent of mRNA translation and mRNA stability. Furthermore, we show that histone H3 lysine 9 trimethylation is one of the mechanisms responsible for the codon usage-mediated transcriptional silencing of some genes with nonoptimal codons. Together, these results uncovered an unexpected important role of codon usage in ORF sequences in determining transcription levels and suggest that codon biases are an adaptation of protein coding sequences to both transcription and translation machineries. Therefore, synonymous codons not only specify protein sequences and translation dynamics, but also help determine gene expression levels.

scholarly journals Evaluation of UHRF1 and P16INK4A expression levels in newly diagnosed AML patients

2018 ◽  
Vol 5 (9) ◽  
pp. 2658-2663 ◽  
Author(s):  
Vahid Amiri ◽  
Mohamadhossein Mohammadi ◽  
Mohammad Reza Khosravi Farsani ◽  
Arshia Gharehbaghian ◽  
Abbas Hajifathali ◽  
...  
Keyword(s):  
Gene Expression ◽  
Negative Correlation ◽  
Leukemic Cells ◽  
Control Group ◽  
Newly Diagnosed ◽  
Expression Levels ◽  
Age Related ◽  
P16ink4a Gene ◽  
The Impact ◽  
Gene Expression Levels

Introduction: Gene mutation is an infrequent cause of tumor suppressor gene (TSG) defect in de novo AML patients. Instead, it seems that leukemic cells employ epigenetic tricks to attenuate the negative impacts of intact TSGs. Ordinarily, critical TSGs, such as p16INK4A, is hyper-methylated in AML blasts under the impact of master epigenetic regulators, such as UHRF1. In this study, we investigated the correlation between UHRF1 and p16INK4A gene expression levels in newly diagnosed AML patients. Methods: Bone marrow and peripheral blood samples were obtained from 50 newly diagnosed AML patients and 18 healthy normal control subjects. Gene expression levels of UHRF1 and P16INK4A were surveyed using SYBR Green Quantitative Real-time PCR. Statistical analyses were done using SPSS statistical software 21.0. Results: P16INK4A gene expression showed reduced levels in 80.64% of patients above 45 years of age, while only 32% of patients below 45 years had reduced expression levels. The Spearman correlation test also demonstrated a significant negative correlation between UHRF1 and p16INK4A gene expression levels in AML patients, which was not observed in the control group (r=0.343 and P= 0.015). Conclusion: Regarding the age-related patterns of UHRF1 and p16INK4A gene expression, and also the presence of negative correlation between them, we conclude that UHRF1 may potentially be involved in p16INK4A down-regulation in elderly AML patients, which may subsequently facilitate the progression of AML in older ages.  

scholarly journals Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling

2021 ◽  
Vol 22 (16) ◽  
pp. 8485
Author(s):  
Iranzu Gómez de Segura ◽  
Patricia Ahechu ◽  
Javier Gómez-Ambrosi ◽  
Amaia Rodríguez ◽  
Beatriz Ramírez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Extracellular Matrix ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Mrna Levels ◽  
Expression Levels ◽  
The Impact ◽  
Ht 29 ◽  
Gene Expression Levels

Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. Results: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 α3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.

The basal subtype to predict clinical benefit from neoadjuvant chemotherapy: Final results from a phase II clinical trial of DDMVAC plus bevacizumab.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 291-291 ◽  
Author(s):  
Arlene O. Siefker-Radtke ◽  
Woonyoung Choi ◽  
Sima P. Porten ◽  
Yu Shen ◽  
Ashish M. Kamat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Neoadjuvant Chemotherapy ◽  
Bone Metastases ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Urothelial Cancer ◽  
Basal Subtype ◽  
Clinical Trial Results ◽  
The Impact

291 Background: Gene expression profiling (GEP) suggests 3 main subtypes of urothelial cancer: basal, which historically has the worst prognosis with high proliferation and HIF-1 expression; p53-like, with decreased proliferation and increased markers of extracellular matrix (ECM); and luminal which has increased proliferation compared to p53-like tumors. We hypothesized that GEP of transurethral resections (TUR) and cystectomy specimens from patients on a neoadjuvant trial would predict benefit from chemotherapy. Methods: Sixty patients enrolled on a neoadjuvant trial of DDMVAC+B. TUR and cystectomy specimens were available for gene expression profiling in 39 and 33 patients, respectively, with matched specimens in 23 patients. The validation set consisted of 49 patients treated with perioperative MVAC on a previously published clinical trial. Results: Chemotherapy was quite active with pT0N0 and ≤ pT1N0 down-staging rates of 38% and 53%, respectively. Basal tumors had improved survival compared to luminal and p53-like (5-year OS 91%, 73% and 36%, p=0.015). A validation cohort of patients treated with perioperative MVAC confirmed this survival benefit (5-year OS basal, luminal, and p53-like 77%, 57%, and 57%, respectively, p =0.027). The use of bevacizumab in basal tumors did not confirm evidence of significant benefit in these small numbers of patients (5-year OS bevacizumab: 91% vs MVAC: 77%, p=0.68) Bone metastases within 2 years associated exclusively with the p53-like subtype (p53-like: 100%, luminal: 0%, basal 0%, p≤0.001). The p53-like subtype was enriched at cystectomy (basal to p53-like in 3/5 (60%), luminal to p53-like in 5/7 (71%), suggesting chemo-resistance in p53-like tumors. Conclusions: In contrast to historical expectations, the basal subtype was predictive of clinical outcomes from neoadjuvant chemotherapy, reflecting the impact of chemotherapy on highly proliferative tumors. Bone metastases were associated with the p53-like subtype which is enriched for ECM. We can no longer think of urothelial cancer as one disease; subtyping should be considered for all tumors, and may have implications on selecting therapy. Clinical trial information: NCT00506155.

Genetic variants in R-Spondin/RNF43 complex and gene expression levels to predict efficacy of cetuximab (cet) in patients (pts) with metastatic colorectal cancer (mCRC): Data from the FIRE-3 phase III trial.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 190-190
Author(s):  
Francesca Battaglin ◽  
Yi Xiao ◽  
Joshua Millstein ◽  
Andreas Seeber ◽  
Hiroyuki Arai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Variants ◽  
Multivariable Analysis ◽  
Colorectal Carcinogenesis ◽  
Phase Iii ◽  
First Line ◽  
Tissue Samples ◽  
Expression Levels ◽  
The Impact ◽  
Gene Expression Levels

190 Background: Wnt signaling deregulation is a primary driver of colorectal carcinogenesis. RNF43 is a key suppressor of Wnt activation while R-Spodin inhibits RNF43 activity. RNF43 mutations are associated with the serrated neoplasia pathway, BRAF mutation and MSI. We hypothesized that genetic variants in the R-Spodin/RNF43 complex and corresponding genes expression levels may predict cetuximab efficacy in mCRC pts. Methods: Genomic DNA from blood samples of pts enrolled in the randomized FIRE-3 trial was genotyped through the OncoArray, a custom array manufactured by Illumina. The impact on outcome of 17 functional SNPs within RNF43/ ZNRF3, LGR4/5 and RSPO1/2/3 was analyzed in 129 pts treated with first-line FOLFIRI/cet and 107 pts treated with FOLFIRI/bevacizumab (bev). Gene expression levels were measured from tumor tissue samples from 102 pts in the cet arm by HTG EdgeSeq Oncology Biomarker Panel. False discovery rate (FDR) for gene expression analysis was computed using the Benjamini-Hochberg approach (significant Q < 0.1). Results: In the cet cohort, pts with the C/C genotype of ZNRF3 rs132531 had significantly shorter overall survival compared to any T allele carriers (mOS: 20.3 vs 52 mo) in both univariable (HR 3.61, 95% CI 1.65-7.88, P < .001) and multivariable analysis (adjusted P = .01). Conversely, RSPO1 rs4652964 any G allele carriers showed increased tumor response (TR) rates compared to the A/A genotype (83 vs 66 %, P = .04). These associations were not observed in bev arm. Lower gene expression levels of RNF43 were associated with shorter PFS in pts with right-sided tumors receiving FOLFIRI/cet ( P = .006, Q < 0.1). RSPO1 expression levels were also associated with TR in the same subgroup (70 vs 10% in high vs low; P = .001, Q < .05). RNF43 expression was associated with TR in pts with left-sided tumors (82% in high vs 58% in low, P = .014, Q = 0.1). Conclusions: Our results provide the first evidence that germline polymorphisms and tumor gene expression levels of RNF43/ ZNRF3 and RSPO1 may have a predictive value in mCRC pts receiving first-line cetuximab-based treatment and contribute to modulate anti-EGFRs activity.

Gene Expression Profiling in Extranodal NK/T-Cell Lymphoma

2020 ◽  
Author(s):  
Ji Yun Lee ◽  
Joo Hyun Kim ◽  
Heejin Bang ◽  
Junhun Cho ◽  
Young Hyeh Ko ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Gene Expression Profiling ◽  
Natural Killer ◽  
Expression Profiling ◽  
Target Genes ◽  
Prognostic Markers ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
Expression Levels

Abstract Extranodal natural killer T-cell lymphoma (ENKTL) is an aggressive malignancy with a dismal prognosis. In the present study, gene expression profiling was performed to provide more information on ENKTL molecular signature and offer a rationale for further investigation of prognostic markers in ENKTL. NanoString nCounter Analysis encompassing 133 target genes was used to compare gene expression levels of 43 ENKTL tumor samples. The majority of the patients were under 60 years of age (79.1%); 32 (74.4%) patients had nasal type ENKTL and 23 patients (53.5%) had intermediate/high risk ENKTL based on the prognostic index for natural killer cell lymphoma (PINK). The median follow-up was 15.9 months and the median overall survival (OS) was 16.1 months (95% CI, 13.0–69.8). EGR1 upregulation was consistently identified in the localized stage with a low risk of prognostic index based on the PINK. Among the six significantly relevant genes for EGR1 expression, high expression levels of genes, including CD59, GAS1, CXCR7, and RAMP3, were associated with a good survival prognosis. The in vitro test showed EGR1 modulated the transcriptional activity of the target genes including CD59, GAS1, CXCR7, and RAMP3. Downregulation of EGR1 and its target genes significantly inhibited apoptosis and decreased chemosensitivity and attenuated radiation-induced apoptosis. The findings showed EGR1 may be a candidate for prognostic markers in ENKTL. Considerable additional characterization may be necessary to fully understand EGR1.

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