scholarly journals BRAFnon-V600E more frequently co-occurs with IDH1/2 mutations in adult patients with gliomas than in patients harboring BRAFV600E but without a survival advantage

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Wang ◽  
Maode Wang ◽  
Haitao Jiang ◽  
Tuo Wang ◽  
Rong Da
Keyword(s):  
Survival Advantage ◽  
The Cancer Genome Atlas ◽  
Molecular Characteristics ◽  
Cancer Type ◽  
Loop Groups ◽  
Significant Difference ◽  
Activation Segment ◽  
Using Data ◽  
Homozygous Deletions ◽  
Adult Glioma

Abstract Background The effects of BRAFnon-V600E and BRAFV600E on the outcomes and the molecular characteristics of adult glioma patients are unknown and need to be explored, although BRAFV600E has been extensively studied in pediatric glioma. Methods Co-occurring mutations and copy number alterations of associated genes in the MAPK and p53 pathways were investigated using data from The Cancer Genome Atlas (TCGA) public database retrieved by cBioPortal. The prognosis of available adult glioma cohorts with BRAFV600E and BRAFnon-V600E mutations were also investigated. Results Ninety patients with BRAFV600E or BRAFnon-V600E were enrolled in this study, and data from 52 nonredundant patients were investigated. Glioblastoma multiform was the most common cancer type, with BRAFnon-V600E and BRAFV600E. TP53 (56.00% vs. 7.41%), IDH1/2 (36.00% vs. 3.70%), and ATRX (32.00% vs. 7.41%) exhibited more mutations in BRAFnon-V600E than in BRAFV600E, and TP53 was an independent risk factor (56.00% vs. 7.41%). Both BRAFnon-V600E and BRAFV600E frequently overlapped with CDKN2A/2B homozygous deletions (HDs), but there was no significant difference. Survival analysis showed no difference between the BRAFnon-V600E and BRAFV600E cohorts, even after excluding the survival benefit of IDH1/2 mutations and considering the BRAFnon-V600E mutations in the glycine-rich loop (G-loop) and in the activation segment. The estimated mean survival of patients with BRAFnon-V600E & IDH1/2WT with mutations in the G-loop groups was the shortest. Conclusions BRAFnon-V600E exhibited a stronger association with IDH1/2 mutations than BRAFV600E, but no survival advantage was found.

scholarly journals BRAFnon-V600E more frequently co-occurs with IDH1/2 mutation in adult patients with gliomas than patients harboring BRAFV600E, but without survival advantage

2021 ◽  
Author(s):  
Rong Da ◽  
Maode Wang ◽  
Haitao Jiang ◽  
Tuo Wang ◽  
Wei Wang
Keyword(s):  
Survival Advantage ◽  
Molecular Characteristics ◽  
Cancer Type ◽  
Loop Groups ◽  
Pediatric Glioma ◽  
Significant Difference ◽  
Activation Segment ◽  
Homozygous Deletions ◽  
Common Cancer Type ◽  
Adult Glioma

Abstract Background The effect of BRAFnon−V600E and BRAFV600E on the outcome and the molecular characteristics in adult glioma patients is unknown and needs to be explored, although BRAFV600E has been extensively studied in pediatric glioma. Methods Co-occurring mutations and copy number alterations of associated genes in the MAPK and p53 pathways were retrieved and investigated using the cBioPortal. The prognosis of available adult glioma cohorts with BRAFV600E and BRAFnon−V600E mutations was also investigated. Results Glioblastoma multiform was the most common cancer type with BRAF non−V600E and BRAFV600E. TP53 (56.00% vs. 7.41%), IDH1/2 (36.00% vs. 3.70%), and ATRX (32.00% vs. 7.41%) exhibited more mutations in BRAFnon−V600E than in BRAFV600E, and TP53 was the independent risk factor (56.00% vs. 7.41%). Both BRAFnon−V600E and BRAFV600E frequently overlapped with CDKN2A/2B homozygous deletions (HD), whereas there was no significant difference. Survival analysis showed no difference between BRAF non−V600E and BRAFV600E cohorts, even excluded the effects of IDH1/2 mutations, and concerned the BRAFnon−V600E mutations in the glycine-rich loop (G-loop) and in the activation segment. The estimated mean survival of BRAFnon−V600E and IDH1/2WT with mutations in the G-loop groups was the shortest. Conclusions BRAF non−V600E exhibited a higher association with IDH1/2 mutation than BRAFV600E, but no survival advantage was found.

scholarly journals Pan-Cancer Analysis Reveals Distinct Metabolic Reprogramming in Different Epithelial–Mesenchymal Transition Activity States

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1778
Author(s):  
Ji-Yong Sung ◽  
Jae-Ho Cheong
Keyword(s):  
Energy Metabolism ◽  
Epithelial Mesenchymal Transition ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Cancer Type ◽  
Mesenchymal Transition ◽  
Significant Difference ◽  
Cancer Types ◽  
Using Data ◽  
Patient Prognosis

Epithelial–mesenchymal transition (EMT) is critical for cancer development, invasion, and metastasis. Its activity influences metabolic reprogramming, tumor aggressiveness, and patient survival. Abnormal tumor metabolism has been identified as a cancer hallmark and is considered a potential therapeutic target. We profiled distinct metabolic signatures by EMT activity using data from 9452 transcriptomes across 31 different cancer types from The Cancer Genome Atlas. Our results demonstrated that ~80 to 90% of cancer types had high carbohydrate and energy metabolism, which were associated with the high EMT group. Notably, among the distinct EMT activities, metabolic reprogramming in different immune microenvironments was correlated with patient prognosis. Nine cancer types showed a significant difference in survival with the presence of high EMT activity. Stomach cancer showed elevated energy metabolism and was associated with an unfavorable prognosis (p < 0.0068) coupled with high expression of CHST14, indicating that it may serve as a potential drug target. Our analyses highlight the prevalence of cancer type-dependent EMT and metabolic reprogramming activities and identified metabolism-associated genes that may serve as potential therapeutic targets.

Genomic profile of gastric cancer in the United States versus East Asia.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 45-45
Author(s):  
Gregory A. Gilmore ◽  
Mohamad Barakat ◽  
Uzair Bashir Chaudhary ◽  
Jeffrey P. Gregg ◽  
Amir Fathi
Keyword(s):  
United States ◽  
Gastric Cancer ◽  
Tumor Biology ◽  
The United States ◽  
The Cancer Genome Atlas ◽  
Cancer Type ◽  
Asian Ethnicity ◽  
Recurrent Mutations ◽  
Significant Difference ◽  
The Us

45 Background: Gastric cancer is the fourth most common cancer type and is the third leading cause of cancer deaths worldwide. Much heterogenicity exists in gastric cancer including geographic variation, with significantly higher incidence in Eastern Asia and a well-known but poorly understood relationship with Asian ethnicity. It has thus been hypothesized that differences in incidence and survival between United States and Asia may be related to a difference in the underlying tumor biology. Methods: We sought to compare the mutational frequencies by comparison of proportions of the 25 most frequent mutations between a US and Chinese population. The US population was derived from The Cancer Genome Atlas (TCGA) PanCancer Atlas comprising 440 patients and the Chinese from a University of Hong Kong Study comprising 100 patients. Results: We found there was a statistically significant difference (P ≤ 0.05) in the frequency of recurrent mutations between US and China population in 14 of the 25 most common genes mutations (table). Conclusions: This data suggests an underlying difference in the mutational profile of gastric cancers in the US as compared with Asia. These findings thus may help to describe the differences in incidence, histology, and outcomes that has been well described in the literature between these two regions of the world. [Table: see text]

scholarly journals MPC-04 MOLECULAR FEATURES AND CLINICAL OUTCOMES OF ELDERLY GLIOBLASTOMA PATIENTS: ANALYSES OF KANSAI NETWORK AND TCGA COHORTS

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii22-ii23
Author(s):  
Junya Fukai ◽  
Hideyuki Arita ◽  
Toru Umehara ◽  
Ema Yoshioka ◽  
Tomoko Shofuda ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Clinical Outcomes ◽  
The Cancer Genome Atlas ◽  
Molecular Characteristics ◽  
Molecular Features ◽  
Negative Prognostic Factor ◽  
Significant Difference ◽  
The Difference ◽  
Potential Factors ◽  
Survival Differences

Abstract INTRODUCTION Aging is a negative prognostic factor in glioblastoma (GB) and the genetic background in clinical outcome of elderly GB could exist. This study investigates the difference of elderly patients from younger ones regarding molecular characteristics as well as clinical outcomes in IDH-wildtype GB. METHODS We collected adult cases diagnosed with IDH-wildtype GB and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network) (212 cases) and The Cancer Genome Atlas (TCGA) project (359 cases). Clinical and pathological characteristics were analyzed retrospectively and compared between elderly cases (≥70 years) and younger ones (≤50 years). Molecular analysis included copy number alterations (CNAs) of eight genes (EGFR, PDGFRA, PTEN, CDKN2A, CDK4, MDM2, TP53, NFKBIA). RESULTS Included in the study were 92 (≥70 years)/33 (≤50 years) cases of Kansai Network and 88 (≥70 years)/69 (≤50 years) cases of TCGA. Median overall survival was 12.8 (≥70 years)/ 21.0 (≤50 years) months in Kansai Network cohort and 8.8 (≥70 years)/ 21.09 (≤50 years) months in TCGA cohort. MGMT promoter was methylated in 50 (54.3%) (≥70 years)/14 (42.4%) (≤50 years) tumors in Kansai Network and 34 (48.6%) (≥70 years)/16 (36.4%) (≤50 years) tumors in TCGA. TERT promoter was mutated in 51 (55.4%) (≥70 years)/13 (39.4%) (≤50 years) tumors in Kansai Network and unknown in TCGA. Significant difference of CNA profiles between ≥70 years and ≤50 years was as follows: PTEN del, 43 (46.7%)/8 (24.2%); CDK4 amp, 17 (18.5%)/1 (3.0%) in Kansai Network and CDKN2A del, 69 (78.4%)/ 42 (60.9%) in TCGA. CONCLUSION Elderly patients have several potential factors for poor prognosis and different molecular profiles might explain the survival differences among generations.

scholarly journals Pan-Cancer Analysis of Alternative Lengthening of Telomere Activity

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2207 ◽  
Author(s):  
Ji-Yong Sung ◽  
Hee-Woong Lim ◽  
Je-Gun Joung ◽  
Woong-Yang Park
Keyword(s):  
Telomerase Activity ◽  
Telomere Maintenance ◽  
The Cancer Genome Atlas ◽  
Cancer Type ◽  
Alternative Lengthening ◽  
Significant Difference ◽  
Cancer Types ◽  
Antigen Presenting ◽  
Telomere Lengthening ◽  
Alt Activity

Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism that extends telomeres in cancer cells. It influences tumorigenesis and patient survival. Despite the clinical significance of ALT in tumors, the manner in which ALT is activated and influences prognostic outcomes in distinct cancer types is unclear. In this work, we profiled distinct telomere maintenance mechanisms (TMMs) using 8953 transcriptomes of 31 different cancer types from The Cancer Genome Atlas (TCGA). Our results demonstrated that approximately 29% of cancer types display high ALT activity with low telomerase activity in the telomere-lengthening group. Among the distinct ALT mechanisms, homologous recombination was frequently observed in sarcoma, adrenocortical carcinoma, and kidney chromophobe. Five cancer types showed a significant difference in survival in the presence of high ALT activity. Sarcoma patients with elevated ALT had unfavorable risks (p < 0.038) coupled with a high expression of TOP2A, suggesting this as a potential drug target. On the contrary, glioblastoma patients had favorable risks (p < 0.02), and showed low levels of antigen-presenting cells. Together, our analyses highlight cancer type-dependent TMM activities and ALT-associated genes as potential therapeutic targets.

scholarly journals Biochemical and molecular characterization of Alternaria alternata isolates highly resistant to procymidone from broccoli and cabbage

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Bingran Wang ◽  
Tiancheng Lou ◽  
Lingling Wei ◽  
Wenchan Chen ◽  
Longbing Huang ◽  
...  
Keyword(s):  
Alternaria Alternata ◽  
Single Point ◽  
Sodium Dodecyl ◽  
Cross Resistance ◽  
Molecular Characteristics ◽  
Single Point Mutation ◽  
Wide Range ◽  
Significant Difference ◽  
Leaf Blights ◽  
High Level

AbstractAlternaria alternata, a causal agent of leaf blights and spots on a wide range of hosts, has a high risk of developing resistance to fungicides. Procymidone, a dicarboximide fungicide (DCF), has been widely used in controlling Alternaria leaf blights in China for decades. However, the resistance of A. alternata against DCFs has rarely been reported from crucifer plants. A total of 198 A. alternata isolates were collected from commercial fields of broccoli and cabbage during 2018–2019, and their sensitivities to procymidone were determined. Biochemical and molecular characteristics were subsequently compared between the high-level procymidone-resistant (ProHR) and procymidone-sensitive (ProS) isolates, and also between ProHR isolates from broccoli and cabbage. Compared with ProS isolates, the mycelial growth rate, sporulation capacity and virulence of most ProHR isolates were reduced; ProHR isolates displayed an increased sensitivity to osmotic stresses and a reduced sensitivity to sodium dodecyl sulfate (SDS); all ProHR isolates showed a reduced sensitivity to hydrogen peroxide (H2O2) except for the isolate B102. Correlation analysis revealed a positive cross-resistance between procymidone and iprodione, or fludioxonil. When treated with 10 μg/mL of procymidone, both mycelial intracellular glycerol accumulations (MIGAs) and relative expression of AaHK1 in ProS isolates were higher than those in ProHR isolates. Sequence alignment of AaHK1 from ten ProHR isolates demonstrated that five of them possessed a single-point mutation (P94A, V612L, E708K or Q924STOP), and four isolates had an insertion or a deletion in their coding regions. No significant difference in biochemical characteristics was observed among ProHR isolates from two different hosts, though mutations in AaHK1 of the cabbage-originated ProHR isolates were distinct from those of the broccoli-originated ProHR isolates.

scholarly journals Performance Comparison of Deep Learning Autoencoders for Cancer Subtype Detection Using Multi-Omics Data

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2013
Author(s):  
Edian F. Franco ◽  
Pratip Rana ◽  
Aline Cruz ◽  
Víctor V. Calderón ◽  
Vasco Azevedo ◽  
...  
Keyword(s):  
Deep Learning ◽  
Data Fusion ◽  
Similarity Measures ◽  
Research Problem ◽  
Optimal Number ◽  
Performance Comparison ◽  
The Cancer Genome Atlas ◽  
Cancer Type ◽  
Omics Data ◽  
Cancer Subtype

A heterogeneous disease such as cancer is activated through multiple pathways and different perturbations. Depending upon the activated pathway(s), the survival of the patients varies significantly and shows different efficacy to various drugs. Therefore, cancer subtype detection using genomics level data is a significant research problem. Subtype detection is often a complex problem, and in most cases, needs multi-omics data fusion to achieve accurate subtyping. Different data fusion and subtyping approaches have been proposed over the years, such as kernel-based fusion, matrix factorization, and deep learning autoencoders. In this paper, we compared the performance of different deep learning autoencoders for cancer subtype detection. We performed cancer subtype detection on four different cancer types from The Cancer Genome Atlas (TCGA) datasets using four autoencoder implementations. We also predicted the optimal number of subtypes in a cancer type using the silhouette score and found that the detected subtypes exhibit significant differences in survival profiles. Furthermore, we compared the effect of feature selection and similarity measures for subtype detection. For further evaluation, we used the Glioblastoma multiforme (GBM) dataset and identified the differentially expressed genes in each of the subtypes. The results obtained are consistent with other genomic studies and can be corroborated with the involved pathways and biological functions. Thus, it shows that the results from the autoencoders, obtained through the interaction of different datatypes of cancer, can be used for the prediction and characterization of patient subgroups and survival profiles.

scholarly journals The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy

2021 ◽  
Vol 18 (9) ◽  
pp. 5038
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Maria Clara La Rosa ◽  
Claudia La Mastra ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pilot Study ◽  
Alcohol Consumption ◽  
Telomere Length ◽  
Molecular Mechanisms ◽  
Epidemiological Studies ◽  
Potential Association ◽  
Significant Difference ◽  
Periconceptional Period ◽  
Using Data

Several studies—albeit with still inconclusive and limited findings—began to focus on the effect of drinking alcohol on telomere length (TL). Here, we present results from a systematic review of these epidemiological studies to investigate the potential association between alcohol consumption, alcohol-related disorders, and TL. The analysis of fourteen studies—selected from PubMed, Medline, and Web of Science databases—showed that people with alcohol-related disorders exhibited shorter TL, but also that alcohol consumption per se did not appear to affect TL in the absence of alcohol abuse or dependence. Our work also revealed a lack of studies in the periconceptional period, raising the need for evaluating this potential relationship during pregnancy. To fill this gap, we conducted a pilot study using data and samples form the Mamma & Bambino cohort. We compared five non-smoking but drinking women with ten non-smoking and non-drinking women, matched for maternal age, gestational age at recruitment, pregestational body mass index, and fetal sex. Interestingly, we detected a significant difference when analyzing relative TL of leukocyte DNA of cord blood samples from newborns. In particular, newborns from drinking women exhibited shorter relative TL than those born from non-drinking women (p = 0.024). Although these findings appeared promising, further research should be encouraged to test any dose–response relationship, to adjust for the effect of other exposures, and to understand the molecular mechanisms involved.

scholarly journals Inhibition of Kynurenine Metabolism and Its Effect in Mitochondrial Function in Hepatocellular Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 124-125
Author(s):  
Raul Castro-Portuguez ◽  
Samuel Freitas ◽  
George Sutphin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mitochondrial Function ◽  
De Novo ◽  
Principal Component ◽  
Kynurenine Pathway ◽  
The Cancer Genome Atlas ◽  
Wilcoxon Test ◽  
Nad Synthesis ◽  
Significant Difference ◽  
Kynurenine Metabolism

Abstract Hepatocellular carcinoma (HCC) is the most prevalent cancer in the liver. The majority of ingested tryptophan is processed in the liver through the kynurenine pathway, the endpoint of which is de novo NAD+ biosynthesis. Dysregulation of tryptophan-kynurenine metabolism and NAD+ synthesis may promote mitochondrial malfunction, tumor reprogramming, and carcinogenesis. Using a publicly available gene expression dataset from liver hepatocellular carcinoma (LIHC) samples available through The Cancer Genome Atlas (TCGA; n = 371), we employed Principal Component Analysis (PCA), hierarchical clustering, gene-pattern expression profiling, and survival analysis to cluster patients and determine overall survival. Our analysis of genes encoding kynurenine pathway enzymes determined that patients with high QPRT expression had a poor prognosis with decreased median survival, with no effect on the maximum survival. There is a significant difference in the survival between patients with high QPRT expression relative to patients with high HAAO/AFMID expression (HR = 1.2, [95% CI 0.5-1.8] P = 0.0181, Gehan-Breslow-Wilcoxon Test). Patients with high QPRT expression have higher survival rates compared with low QPRT expression (HR = 1.4, [95% CI 0.9-2.2] P = 0.0344, Gehan-Breslow-Wilcoxon Test). To test the consequences of kynurenine-pathway inhibition in mitochondrial function and morphology we use 4-Cl-3HAA, an irreversible HAAO inhibitor, and observed a small increase in mitochondrial fragmentation in HepG2 cells after 24 hours of treatment. We conclude that kynurenine metabolism may be useful as a biomarker to predict patient prognosis among HCC patients. In ongoing work, we are testing QPRT inhibitors in cell culture as a potential adjuvant for chemotherapies.

scholarly journals Lockdown, slow down: impact of the COVID-19 pandemic on physical activity—an observational study

Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001600
Author(s):  
Joanne Kathryn Taylor ◽  
Haarith Ndiaye ◽  
Matthew Daniels ◽  
Fozia Ahmed
Keyword(s):  
Physical Activity ◽  
New York ◽  
Heart Association ◽  
Evaluation Study ◽  
Activity Data ◽  
Cardiac Devices ◽  
Significant Difference ◽  
New York Heart Association ◽  
Using Data ◽  
The Uk

AimsIn response to the COVID-19 pandemic, the UK was placed under strict lockdown measures on 23 March 2020. The aim of this study was to quantify the effects on physical activity (PA) levels using data from the prospective Triage-HF Plus Evaluation study.MethodsThis study represents a cohort of adult patients with implanted cardiac devices capable of measuring activity by embedded accelerometery via a remote monitoring platform. Activity data were available for the 4 weeks pre-implementation and post implementation of ‘stay at home’ lockdown measures in the form of ‘minutes active per day’ (min/day).ResultsData were analysed for 311 patients (77.2% men, mean age 68.8, frailty 55.9%. 92.2% established heart failure (HF) diagnosis, of these 51.2% New York Heart Association II), with comorbidities representative of a real-world cohort.Post-lockdown, a significant reduction in median PA equating to 20.8 active min/day was seen. The reduction was uniform with a slightly more pronounced drop in PA for women, but no statistically significant difference with respect to age, body mass index, frailty or device type. Activity dropped in the immediate 2-week period post-lockdown, but steadily returned thereafter. Median activity week 4 weeks post-lockdown remained significantly lower than 4 weeks pre-lockdown (p≤0.001).ConclusionsIn a population of predominantly HF patients with cardiac devices, activity reduced by approximately 20 min active per day in the immediate aftermath of strict COVID-19 lockdown measures.Trial registration numberNCT04177199.

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