Expression Status and Prognostic Roles of m6A-related Genes in Multiple Myeloma: YTHDF2 as the independent prognostic factor

2021 ◽  
Author(s):  
Rui Liu ◽  
Ying Shen ◽  
Xiaman Wang ◽  
Dong Wu ◽  
Meng Zhai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Prognostic Factor ◽  
Molecular Mechanisms ◽  
Roc Curves ◽  
Independent Prognostic Factor ◽  
Differentially Expressed ◽  
Cox Regression Analysis ◽  
Differentially Expressed Mrna ◽  
Expression Status

Abstract Background: N6-methyladenosine is the most abundant RNA modification, which plays a prominent role in multiple biology processes, including tumorigenesis. Multiple myeloma (MM) is the second most frequent hematological cancer. However, the expression status and value of m6A-related genes in multiple myeloma remain elusive.Methods: m6A-related gene expression data and clinical information of MM patients were obtained from the Gene Expression Omnibus (GEO) database. Based on differentially expressed analysis, protein-protein interaction (PPI) analysis, Pearson correlation analysis, Kaplan-Meier survival analysis and Cox regression analysis, the prognostic m6A-associated genes were identified. The receiver operation characteristic (ROC) curves were used to verify the prognostic and diagnostic efficiency. The molecular mechanisms were investigated by differentially expressed mRNA and microRNA analyses with the help of online database ENCORI and POSTAR.Results: Among 22 m6A-related genes, HNRNPC, RBM15B, RBM15, YTHDF3, YTHDF2, HNRNPA2B1 and IGF2BP2 were significantly upregulated, while ZC3H13, FTO, IGF2BP3, ALKBH5 and YTHDC1 were significantly downregulated in MM patients. The high expression of HNRNPC, HNRNPA2B1, YTHDF2 and the low expression of ZC3H13 were associated with adverse survival. Furthermore, the expression level of YTHDF2 was the independent prognostic factor of MM. ROC curves suggested the great prediction performance for MM patients. Differentially expressed mRNA and microRNA analyses indicated the probable involvement of miR-205/YTHDF2/EGR1 axis.Conclusions: Our study first systematically analyzed the expression status of m6A-related genes in multiple myeloma, identified HNRNPC, HNRNPA2B1, YTHDF2 and ZC3H13 that could be the potential prognostic biomarkers, especially YTHDF2, which may be implicated in the miR-205/YTHDF2/EGR1 axis.

scholarly journals Identification of Potential Biomarkers From Hepatocellular Carcinoma With MT1 Deletion

2021 ◽  
Vol 27 ◽  
Author(s):  
Ruohao Zhang ◽  
Miao Huang ◽  
Hong Wang ◽  
Shengming Wu ◽  
Jiali Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Independent Prognostic Factor ◽  
Comparative Genomic ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Cox Regression Analysis ◽  
Potential Biomarkers

Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. Metallothioneins (MTs) are metal-binding proteins involved in multiple biological processes such as metal homeostasis and detoxification, as well as in oncogenesis. Copy number variation (CNV) plays a vital role in pathogenesis and carcinogenesis. Nevertheless, there is no study on the role of MT1 CNV in HCC.Methods: Array-based Comparative Genomic Hybridization (aCGH) analysis was performed to obtain the CNV data of 79 Guangxi HCC patients. The prognostic effect of MT1-deletion was analyzed by univariate and multivariate Cox regression analysis. The differentially expressed genes (DEGs) were screened based on The Gene Expression Omnibus database (GEO) and the Liver Hepatocellular Carcinoma of The Cancer Genome Atlas (TCGA-LIHC). Then function and pathway enrichment analysis, protein-protein interaction (PPI) and hub gene selection were applied on the DEGs. Lastly, the hub genes were validated by immunohistochemistry, tissue expression and prognostic analysis.Results: The MT1-deletion was demonstrated to affect the prognosis of HCC and can act as an independent prognostic factor. 147 common DEGs were screened. The most significant cluster of DEGs identified by Molecular Complex Detection (MCODE) indicated that the expression of four MT1s were down-regulated. MT1X and other five hub genes (TTK, BUB1, CYP3A4, NR1I2, CYP8B1) were associated with the prognosis of HCC. TTK, could affect the prognosis of HCC with MT1-deletion and non-deletion. NR1I2, CYP8B1, and BUB1 were associated with the prognosis of HCC with MT1-deletion.Conclusions: In the current study, we demonstrated that MT1-deletion can be an independent prognostic factor in HCC. We identified TTK, BUB1, NR1I2, CYP8B1 by processing microarray data, for the first time revealed the underlying function of MT1 deletion in HCC, MT1-deletion may influence the gene expression in HCC, which may be the potential biomarkers for HCC with MT1 deletion.

Insights into the seasonal adaptive mechanisms of Chinese alligators (Alligator sinensis) from transcriptomic analyses

2018 ◽  
Vol 66 (2) ◽  
pp. 93 ◽  
Author(s):  
Hongji Sun ◽  
Xianbo Zuo ◽  
Long Sun ◽  
Peng Yan ◽  
Fang Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Differentially Expressed ◽  
Model Organisms ◽  
Seasonal Adaptation ◽  
Cold Temperatures ◽  
Chinese Alligator ◽  
Adaptive Mechanisms ◽  
Alligator Sinensis

The Chinese alligator (Alligator sinensis) is an endemic and rare species in China, and is considered to be one of the most endangered vertebrates in the world. It is known to hibernate, an energy-saving strategy against cold temperatures and food deprivation. Changes in gene expression during hibernation remain largely unknown. To understand these complex seasonal adaptive mechanisms, we performed a comprehensive survey of differential gene expression in heart, skeletal muscle, and kidney of hibernating and active Chinese alligators using RNA-Sequencing. In total, we identified 4780 genes differentially expressed between the active and hibernating periods. GO and KEGG pathway analysis indicated the likely role of these differentially expressed genes (DEGs). The upregulated DEGs in the active Chinese alligator, CSRP3, MYG and PCKGC, may maintain heart and skeletal muscle contraction, transport and storage of oxygen, and enhance the body’s metabolism, respectively. The upregulated DEGs in the dormant Chinese alligator, ADIPO, CIRBP and TMM27, may improve insulin sensitivity and glucose/lipid metabolism, protect cells against harmful effects of cold temperature and hypoxia, regulate amino acid transport and uptake, and stimulate the proliferation of islet cells and the secretion of insulin. These results provide a foundation for understanding the molecular mechanisms of the seasonal adaptation required for hibernation in Chinese alligators, as well as effective information for other non-model organisms research.

scholarly journals Insight into Molecular Profile Changes after Skeletal Muscle Contusion Using Microarray and Bioinformatics Analyses

2020 ◽  
Author(s):  
Na Li ◽  
Ru-feng Bai ◽  
Chun Li ◽  
Li-hong Dang ◽  
Qiu-xiang Du ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Healing Process ◽  
Differentially Expressed ◽  
Molecular Profile ◽  
Wound Age ◽  
Functional Modules

Abstract Background: Muscle trauma frequently occurs in daily life. However, the molecular mechanisms of muscle healing, which partly depend on the extent of the damage, are not well understood. This study aimed to investigate gene expression profiles following mild and severe muscle contusion, and to provide more information about the molecular mechanisms underlying the repair process.Methods: A total of 33 rats were divided randomly into control (n = 3), mild contusion (n = 15), and severe contusion (n = 15) groups; the contusion groups were further divided into five subgroups (1, 3, 24, 48, and 168 h post-injury; n = 3 per subgroup). Then full genome microarray of RNA isolated from muscle tissue was performed to access the gene expression changes during healing process.Results: A total of 2,844 and 2,298 differentially expressed genes were identified in the mild and severe contusion groups, respectively. The analysis of the overlapping differentially expressed genes showed that there are common mechanisms of transcriptomic repair of mild and severe contusion within 48 h post-contusion. This was supported by the results of principal component analysis, hierarchical clustering, and weighted gene co‐expression network analysis of the 1,620 coexpressed genes in mildly and severely contused muscle. From these analyses, we discovered that the gene profiles in functional modules and temporal clusters were similar between the mild and severe contusion groups; moreover, the genes showed time-dependent patterns of expression, which allowed us to identify useful markers of wound age. We then performed an analysis of the functions of genes (including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway annotation, and protein–protein interaction network analysis) in the functional modules and temporal clusters, and the hub genes in each module–cluster pair were identified. Interestingly, we found that genes downregulated within 24−48 h of the healing process were largely associated with metabolic processes, especially oxidative phosphorylation of reduced nicotinamide adenine dinucleotide phosphate, which has been rarely reported. Conclusions: These results improve our understanding of the molecular mechanisms underlying muscle repair, and provide a basis for further studies of wound age estimation.

scholarly journals Prognostic Value and Regulatory Network of Immune-Related Genes in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Xiang Zhou ◽  
Keying Zhang ◽  
Fa Yang ◽  
Chao Xu ◽  
Jianhua Jiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Risk Model ◽  
Cox Regression ◽  
Wilcoxon Test ◽  
Differentially Expressed ◽  
Cox Regression Analysis ◽  
Immune Related Genes

Abstract Background: Hepatocellular carcinoma (HCC) is a disease with higher morbidity, mortality, and poor prognosis in the whole world. Understanding the crosslink between HCC and the immune system is essential for people to uncover a few potential and valuable therapeutic strategies. This study aimed to reveal the correlation between HCC and immune-related genes and establish a clinical evaluation model. Methods: We had analyzed the clinical information consisted of 373 HCC and 49 normal samples from the cancer genome atlas (TCGA). The differentially expressed genes (DEGs) were selected by the Wilcoxon test and the immune-related differentially expressed genes (IRDEGs) in DEGs were identified by matching DEGs with immune-related genes downloaded from the ImmPort database. Furthermore, the univariate Cox regression analysis and multivariate Cox regression analysis were performed to construct a prognostic risk model. Then, twenty-two types of tumor immune-infiltrating cells (TIICs) were downloaded from Tumor Immune Estimation Resource (TIMER) and were used to construct the correlational graphs between the TIICs and risk score by the CIBERSORT. Subsequently, the transcription factors (TFs) were gained in the Cistrome website and the differentially expressed TFs (DETFs) were achieved. Finally, the KEGG pathway analysis and GO analysis were performed to further understand the molecular mechanisms between DETFs and PDIRGs.Results: In our study, 5839 DEGs, 326 IRDEGs, and 31 prognosis-related IRDEGs (PIRDEGs) were identified. And 8 optimal PIRDEGs were employed to construct a prognostic risk model by multivariate Cox regression analysis. The correlation between risk genes and clinical characterizations and TIICs has verified that the prognostic model was effective in predicting the prognosis of HCC patients. Finally, several important immune-related pathways and molecular functions of the eight PIRDEGs were significantly enriched and there was a distinct association between the risk IRDEGs and TFs. Conclusion: The prognostic risk model showed a more valuable predicting role for HCC patients, and produced many novel therapeutic targets and strategies for HCC.

scholarly journals Identification of a Novel Gene Model-Based Homologous Recombination Deficiency Score to Improve Survival Prediction of TNBC.

2021 ◽  
Author(s):  
Wenxiang Zhang ◽  
Bolun Ai ◽  
Xiangyi Kong ◽  
Xiangyu Wang ◽  
Jie Zhai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Homologous Recombination ◽  
Risk Score ◽  
Cox Regression ◽  
Roc Curves ◽  
Cox Regression Analysis ◽  
Homologous Recombination Deficiency ◽  
Ajcc Stage ◽  
Kaplan Meier

Abstract Background Triple-negative breast cancer (TNBC) is a specific histological type of breast cancer with a poor prognosis, early recurrence, which lacks durable chemotherapy responses and effective targeted therapies. We aimed to construct an accurate prognostic risk model based on homologous recombination deficiency (HRD) - gene expression profiles for improving prognosis prediction of TNBC. Methods Triple-negative breast cancer RNA sequencing data and sample clinical information were downloaded from the breast invasive carcinoma (BRCA) cohort in the Cancer Genome Atlas (TCGA) database. Combined with the HRD database, tumor samples were divided into two sets. We screened differentially expressed genes (DEGs) and then identified HRD-related prognostic genes using weighted gene co-expression network analysis (WGCNA) and Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were used to identifying key prognostic genes. Risk scores were calculated and compared with HRD score, Kaplan–Meier (KM) survival analysis were used to assess its prognostic power. GSE103091 dataset from GEO (Gene Expression Omnibus) database was used to validate the signature. Univariate and multivariate Cox regression were performed to independently verify the prognosis of the risk score. A nomogram was constructed and revealed by time-dependent ROC curves to guide clinical practice. Results We found that HRD tumor samples (HRD score > = 42) in TNBC patients were associated with poor overall survival (p = 0.027). We identified a total of 147 differential genes including 203 up-regulated and 213 down-regulated genes, among which 29 were prognosis-related genes. Through the LASSO method, 6 key prognostic genes ((MUCL1, IVL, FAM46C, CHI3L1, PRR15L, and CLEC3A) were selected and a 6-gene risk score was constructed. We found risk score was negatively associated with homologous recombination deficiency (HRD) scores (r = -0.22, p = 0.019). Compared with the low-risk group, Kaplan-Meier survival analysis shows that the high-risk group has an obvious poorer prognosis (P < 0.0001). Finally, we integrated the risk score model and clinical factors of TNBC (AJCC-stage, HRD score, T stage, and N stage) to construct a compound nomogram. Time-dependent ROC curves showed the risk score performed better in 1-, 3- and 5-year survival predictions compared with AJCC-stage. Conclusions Based on HRD gene expression data, our six HRD-related gene signature and nomogram could be practical and reliable tools for predicting OS in patients with TNBC.

scholarly journals Prognostic Significance of Sarcopenia in Patients with Unresectable Advanced Esophageal Cancer

2019 ◽  
Vol 8 (10) ◽  
pp. 1647 ◽  
Author(s):  
Sachiyo Onishi ◽  
Masahiro Tajika ◽  
Tsutomu Tanaka ◽  
Yutaka Hirayama ◽  
Kazuo Hara ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Japanese Patients ◽  
Independent Prognostic Factor ◽  
Cancer Center ◽  
Advanced Esophageal Cancer ◽  
Cox Regression Analysis ◽  
Group 2

The prognostic significance of sarcopenia in unresectable advanced esophageal cancer remains unclear. Our study retrospectively evaluated 176 consecutive Japanese patients with esophageal squamous cell carcinoma who had been diagnosed with unresectable advanced cancer in Aichi Cancer Center Hospital between January 2007 and December 2014. Skeletal muscle mass was calculated from abdominal computed tomography (CT) scans before treatment, and patients were divided into sarcopenic and non-sarcopenic groups. Sarcopenia was present in 101 patients (57.4%). Eighty-two patients in the sarcopenic group and 63 patients in the non-sarcopenic group died during follow-up (mean: 20.3 months). The overall survival (OS) rate was significantly lower in the sarcopenic group compared to the non-sarcopenic group (2-year OS: 9.8% vs. 23.7%, p < 0.01). Cox regression analysis revealed only pretreatment sarcopenia as an independent prognostic factor (hazard ratio (HR): 1.48, 95% confidence interval (CI): 1.04–2.10, p = 0.03). In the sarcopenic group, withdrawn cases, for whom the planned treatment was discontinued for some reason, showed a significantly lower OS rate compared to complete cases (1-year OS: 11.0% vs. 59.9%, p < 0.01). The most common reason for discontinuation was aspiration pneumonia (64.5%). Presence of sarcopenia was an independent prognostic factor for unresectable advanced esophageal cancer. Identifying the presence of sarcopenia prior to treatment may improve the prognosis.

scholarly journals Positive tumour CD47 expression is an independent prognostic factor for recurrence in resected non-small cell lung cancer

ESMO Open ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. e000823
Author(s):  
Yan Xu ◽  
Ji Li ◽  
Bing Tong ◽  
Minjiang Chen ◽  
Xiaoyan Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factor ◽  
Infectious Diseases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Independent Prognostic Factor ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Resected Nsclc

BackgroundImmunotherapy is a promising advance in oncology. Limited information exists regarding the interrelationship between CD47 expression and tumour-associated macrophage-related immuno-microenvironment in patients with non-small cell lung cancer (NSCLC). These factors may predict novel immunotherapy efficacy.Patients and methodsCD47 and PD-L1 expression was retrospectively assessed in 191 resected NSCLC specimens via immunohistochemistry. Forty-six patients with pulmonary infectious diseases were enrolled as the control group. The infiltration of macrophages (M2 and M1) and CD8+ T-lymphocytes was evaluated via dual-immunofluorescence staining. Targeted DNA sequencing was performed on NSCLC specimens. Survival analysis was performed using the Cox model.ResultsUsing 2+/3+ as a CD47 positive (CD47pos) expression cut-off, the prevalence of CD47pos expression in NSCLC was 33.0% (63/191), significantly higher than in pulmonary infectious diseases. CD47pos expression was significantly higher in female, non-smoking and adenocarcinoma patients (p=0.020, p<0.001 and p<0.001, respectively). Furthermore, CD47pos expression was significantly correlated with epidermal growth factor receptor mutation (p<0.001). The expression of CD47 (H-score) in NSCLC was negatively correlated with tumour PD-L1 expression (p=0.0346) and tumour mutation burden (p=0.0107). CD47pos expression was independently correlated with poor disease-free survival in patients with resected NSCLC in multivariate Cox regression analysis (p=0.035).ConclusionThis study revealed the demographic, molecular and immuno-microenvironment characteristics of CD47 expression in NSCLC. We identified tumour CD47pos expression as an independent prognostic factor for recurrence in resected NSCLC. Our findings illustrate the potential of anti-CD47 treatment in NSCLC.

Socioeconomic Status Is an Independent Prognostic Factor for Overall Survival in Patients With Multiple Myeloma: Real-World Data From a Cohort of 223 Patients

2020 ◽  
Vol 20 (10) ◽  
pp. 704-711
Author(s):  
Stergios Intzes ◽  
Marianthi Symeonidou ◽  
Konstantinos Zagoridis ◽  
Zoe Bezirgiannidou ◽  
Aikaterini Pentidou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Socioeconomic Status ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Real World ◽  
Independent Prognostic Factor ◽  
Real World Data ◽  
World Data

scholarly journals Gene expression vs. sequence divergence: comparative transcriptome sequencing among natural Rhinolophus ferrumequinum populations with different acoustic phenotypes

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Hanbo Zhao ◽  
Hui Wang ◽  
Tong Liu ◽  
Sen Liu ◽  
Longru Jin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Geographic Variation ◽  
Molecular Mechanisms ◽  
Sequence Divergence ◽  
Orthologous Gene ◽  
Differentially Expressed ◽  
Nucleotide Polymorphisms ◽  
Genetic Lineages ◽  
Rhinolophus Ferrumequinum ◽  
Horseshoe Bat

Abstract Background Although the sensory drive hypothesis can explain the geographic variation in echolocation frequencies of some bat species, the molecular mechanisms underlying this phenomenon are still unclear. The three lineages of greater horseshoe bat (Rhinolophus ferrumequinum) in China (northeast, central-east, and southwest) have significant geographic variation in resting frequencies (RF) of echolocation calls. Because their cochleae have an acoustic fovea that is highly sensitive to a narrow range of frequencies, we reported the transcriptomes of cochleae collected from three genetic lineages of R. ferrumequinum, which is an ideal organism for studying geographic variation in echolocation signals, and tried to understand the mechanisms behind this bat phenomenon by analyzing gene expression and sequence variation. Results A total of 8190 differentially expressed genes (DEGs) were identified. We identified five modules from all DEGs that were significantly related to RF or forearm length (FL). DEGs in the RF-related modules were significantly enriched in the gene categories involved in neural activity, learning, and response to sound. DEGs in the FL-related modules were significantly enriched in the pathways related to muscle and actin functions. Using 21,945 single nucleotide polymorphisms, we identified 18 candidate unigenes associated with hearing, five of which were differentially expressed among the three populations. Additionally, the gene ERBB4, which regulates diverse cellular processes in the inner ear such as cell proliferation and differentiation, was in the largest module. We also found 49 unigenes that were under positive selection from 4105 one-to-one orthologous gene pairs between the three R. ferrumequinum lineages and three other Chiroptera species. Conclusions The variability of gene expression and sequence divergence at the molecular level might provide evidence that can help elucidate the genetic basis of geographic variation in echolocation signals of greater horseshoe bats.

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