scholarly journals ITGB2 Expression is Negatively Correlated with the Prognosis of Acute Myeloid Leukemia

2021 ◽  
Author(s):  
Jianan Zhou ◽  
Bobin Chen ◽  
Pei Li
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Regression Analysis ◽  
Mast Cells ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
Ppi Network ◽  
Cox Regression Analysis ◽  
Acute Myeloid

Abstract Objective: Acute myeloid leukemia (AML) is a clonal malignant hematological neoplasm with a poor prognosis and high heterogeneity. Many studies have been conducted on the diagnosis and treatment of AML, but the immune microenvironmental mechanisms underlying AML disease progression have not been fully elucidated. The aim of this study was to find the potential genes in tumor microenvironmental mechanisms underlying the initiation and progression of AML through relevant biological informatics analysis, and investigate the potential influence of the gene in tumor microenvironment (TME).Methods: AML samples of genes were retrieved from The Cancer Genome Atlas (TCGA) databases. The number of tumor-infiltrating immune cells (TIC) as well as immune and stromal components in AML cases was calculated using the ESTIMATE and CIBERSORT algorithms. Two methods, COX regression analysis and protein-protein interaction (PPI) network, were applied to obtain related genes, and the intersection of related genes was taken to obtain differentially expressed genes (DEGs). Gene Set Enrichment Analysis (GSEA) was used for explore the biological signaling pathway. CIBERSORT analysis for the proportion of TICs was performed to reveal that TICs which are related of the target gene.Results: Cross-tabulation analysis of univariate COX regression analysis and PPI network known the β2 integrin factor (ITGB2) as a major predictor of AML prognosis. High expression of ITGB2 was correlated with low survival of AML patients. GSEA revealed that the higher the ITGB2 gene expression, the more active the immune-related activity. CIBERSORT analysis of the TICs ratio revealed that 9 kinds of TICs were negatively correlated with the expression of ITGB2, including CD4 memory resting T cells, CD8 T cells, naive B cells, resting NK cells, Plasma cells, follicular helper T cells, resting Mast cells, Eosinophils and activated mast cells. Only monocytes were positively correlated with ITGB2 expression. These results provided further evidence that ITGB2 levels may determine the prognosis of AML patients by modulating the immune status of TME, which provides an additional suggestion for the treatment of AML.

scholarly journals Prognosis and Characterization of Immune Microenvironment in Acute Myeloid Leukemia Through Identification of an Autophagy-Related Signature

2021 ◽  
Vol 12 ◽  
Author(s):  
Denggang Fu ◽  
Biyu Zhang ◽  
Shiyong Wu ◽  
Yinghua Zhang ◽  
Jingwu Xie ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Regression Analysis ◽  
High Risk ◽  
Signaling Pathways ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Prognostic Predictor ◽  
Risk Patients ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has an unfavorable outcome and a high rate of relapse. Autophagy plays a vital role in the development of and therapeutic responses to leukemia. This study identifies a potential autophagy-related signature to monitor the prognoses of patients of AML. Transcriptomic profiles of AML patients (GSE37642) with the relevant clinical information were downloaded from Gene Expression Omnibus (GEO) as the training set while TCGA-AML and GSE12417 were used as validation cohorts. Univariate regression analyses and multivariate stepwise Cox regression analysis were respectively applied to identify the autophagy-related signature. The univariate Cox regression analysis identified 32 autophagy-related genes (ARGs) that were significantly associated with the overall survival (OS) of the patients, and were mainly rich in signaling pathways for autophagy, p53, AMPK, and TNF. A prognostic signature that comprised eight ARGs (BAG3, CALCOCO2, CAMKK2, CANX, DAPK1, P4HB, TSC2, and ULK1) and had good predictive capacity was established by LASSO–Cox stepwise regression analysis. High-risk patients were found to have significantly shorter OS than patients in low-risk group. The signature can be used as an independent prognostic predictor after adjusting for clinicopathological parameters, and was validated on two external AML sets. Differentially expressed genes analyzed in two groups were involved in inflammatory and immune signaling pathways. An analysis of tumor-infiltrating immune cells confirmed that high-risk patients had a strong immunosuppressive microenvironment. Potential druggable OS-related ARGs were then investigated through protein–drug interactions. This study provides a systematic analysis of ARGs and develops an OS-related prognostic predictor for AML patients. Further work is needed to verify its clinical utility and identify the underlying molecular mechanisms in AML.

scholarly journals Regulatory Networks of Prognostic mRNAs in Pediatric Acute Myeloid Leukemia

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Hao Zhang ◽  
Liqin Cheng ◽  
Cong Liu
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Score ◽  
Regulatory Network ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Ppi Network ◽  
Pediatric Acute Myeloid Leukemia ◽  
Cox Regression Analysis ◽  
Pediatric Aml ◽  
Acute Myeloid

Acute myeloid leukemia (AML) in children refers to a malignant tumor caused by the abnormal proliferation of immature myeloid cells in the bone marrow and peripheral blood. The prognosis of patients with pediatric acute myeloid leukemia (AML) remains poor, highlighting the need for improved targeted therapy. The expression data of lncRNAs, mRNAs, and miRNAs and survival information of pediatric AML patients were collected from The Cancer Genome Atlas (TCGA) database. Cox regression analysis was used to screen the lncRNAs, mRNAs, and miRNAs that significantly affect the overall survival (OS) of patients as OS-related genes (included lncRNAs, mRNAs, and miRNAs). Enrichment analysis and protein-protein interaction (PPI) network construction were performed for the OS-related mRNAs. We further established a ceRNAs regulatory network. In addition, the potential prognostic role of genes was further evaluated by risk score. We have identified 5275 lncRNAs, 176 miRNAs, and 6221 mRNAs that significantly affect the prognosis of pediatric AML patients. It is worth noting that OS-related mRNAs are mainly involved in ribosome, RNA transport, and spliceosome. We identified the top 10 most connected mRNAs in the PPI network as important mRNAs and constructed a ceRNAs regulatory network (including NCBP2, RPLP0, UBC, RPS2, and RPS9). The risk score and nomogram results suggest that NCBP2 may be a risk factor for pediatric AML, while RPLP0, UBC, RPS2, and RPS9 may be protective factors. Our results construct 5 gene signals as new prognostic indicators for predicting the survival of pediatric AML patients. Our research has demonstrated the ceRNAs regulatory network may become a new target for pediatric AML treatment.

scholarly journals High EVI1 Expression Predicts Adverse Outcomes in Children With De Novo Acute Myeloid Leukemia

2021 ◽  
Vol 11 ◽  
Author(s):  
Yongzhi Zheng ◽  
Yan Huang ◽  
Shaohua Le ◽  
Hao Zheng ◽  
Xueling Hua ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Regression Analysis ◽  
Myeloid Leukemia ◽  
Pediatric Patients ◽  
Cox Regression ◽  
De Novo ◽  
Adverse Outcomes ◽  
Cox Regression Analysis ◽  
Pediatric Aml ◽  
Acute Myeloid

BackgroundA high ecotropic viral integration site 1 (EVI1) expression (EVI1high) is an independent prognostic factor in adult acute myeloid leukemia (AML). However, little is known of the prognostic value of EVI1high in pediatric AML. This study aimed to examine the biological and prognostic significance of EVI1high in uniformly treated pediatric patients with AML from a large cohort of seven centers in China.MethodsA diagnostic assay was developed to determine the relative EVI1 expression using a single real-time quantitative polymerase chain reaction in 421 newly diagnosed pediatric AML patients younger than 14 years from seven centers in southern China. All patients were treated with a uniform protocol, but only 383 patients were evaluated for their treatment response. The survival data were included in the subsequent analysis (n = 35 for EVI1high, n = 348 for EVI1low).ResultsEVI1high was found in 9.0% of all 421 pediatric patients with de novo AML. EVI1high was predominantly found in acute megakaryoblastic leukemia (FAB M7), MLL rearrangements, and unfavorable cytogenetic aberrance, whereas it was mutually exclusive with t (8; 21), inv (16)/t (16; 16), CEBPA, NPM1, or C-KIT mutations. In the univariate Cox regression analysis, EVI1high had a significantly adverse 5-year event-free survival (EFS) and overall survival (OS) [hazard ratio (HR) = 1.821 and 2.401, p = 0.036 and 0.005, respectively]. In the multivariate Cox regression analysis, EVI1high was an independent prognostic factor for the OS (HR = 2.447, p = 0.015) but not EFS (HR = 1.556, p = 0.174). Furthermore, EVI1high was an independent adverse predictor of the OS and EFS of patients with MLL rearrangements (univariate analysis: HR = 9.921 and 7.253, both p < 0.001; multivariate analysis: HR = 7.186 and 7.315, p = 0.005 and 0.001, respectively). Hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) provided EVI1high patients with a tendential survival benefit when compared with chemotherapy as a consolidation (5-year EFS: 68.4% vs. 50.8%, p = 0.26; 5-year OS: 65.9% vs. 54.8%, p = 0.45).ConclusionIt could be concluded that EVI1high can be detected in approximately 10% of pediatric AML cases. It is predominantly present in unfavorable cytogenetic subtypes and predicts adverse outcomes. Whether pediatric patients with EVI1high AML can benefit from HSCT in CR1 needs to be researched further.

scholarly journals Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5824-5831 ◽  
Author(s):  
Ana Flávia Tibúrcio Ribeiro ◽  
Marta Pratcorona ◽  
Claudia Erpelinck-Verschueren ◽  
Veronika Rockova ◽  
Mathijs Sanders ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Gene Expression Signature ◽  
Mutation Status ◽  
Cox Regression Analysis ◽  
Prognostic Effect ◽  
Or Gene ◽  
Acute Myeloid

Abstract The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3Amutant AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3Awild-type AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations, this association is particularly evident (OS: P = .013; HR, 2.09; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3Amutant AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3Awild-type AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.

scholarly journals Expression Levels of Human Equilibrative Nucleoside Transporter 1 and Deoxycytidine Kinase Enzyme as Prognostic Factors in Patients with Acute Myeloid Leukemia Treated with Cytarabine

Chemotherapy ◽  
2016 ◽  
Vol 61 (6) ◽  
pp. 313-318 ◽  
Author(s):  
Myrna Candelaria ◽  
Carmen Corrales-Alfaro ◽  
Olga Gutiérrez-Hernández ◽  
José Díaz-Chavez ◽  
Juan Labardini-Méndez ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Performance Status ◽  
Deoxycytidine Kinase ◽  
Nucleoside Transporter ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Equilibrative Nucleoside Transporter ◽  
Acute Myeloid

Background: Cytarabine (Ara-C) is the primary drug in different treatment schemas for acute myeloid leukemia (AML) and requires the human equilibrative nucleoside transporter (hENT1) to enter cells. The deoxycytidine kinase (dCK) enzyme limits its activation rate. Therefore, decreased expression levels of these genes may influence the response rate to this drug. Methods: AML patients without previous treatment were enrolled. The expression of hENT1 and dCK genes was analyzed using RT-PCR. Clinical parameters were registered. All patients received Ara-C + doxorubicin as an induction regimen (7 + 3 schema). Descriptive statistics were used to analyze data. Uni- and multivariate analyses were performed to determine factors that influenced response and survival. Results: Twenty-eight patients were included from January 2011 until December 2012. Median age was 36.5 years. All patients had an adequate performance status (43% with ECOG 1 and 57% with ECOG 2). Cytogenetic risk was considered unfavorable in 54% of the patients. Complete response was achieved in 53.8%. Cox regression analysis showed that a higher hENT1 expression level was the only factor that influenced response and survival. Conclusions: These results highly suggest that the pharmacogenetic analyses of Ara-C influx may be decisive in AML patients.

scholarly journals High Expression of PXN Predicts a Poor Prognosis in Acute myeloid leukemia

2021 ◽  
Author(s):  
xinwen zhang ◽  
Hao Xiong ◽  
Jialin Duan ◽  
Xiaomin Chen ◽  
Yang Liu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Receive Treatment ◽  
To Receive ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is one of the common malignant diseases of hematopoietic system. Paxillin ( PXN ) is an important part of focal adhesions (FAs), which is related to the poor prognosis of many kinds of malignant tumors. However, no research has focused on the expression of PXN in AML. We aimed to investigate the expression of PXN in AML and its prognostic significance. Methods: Using GEPIA and UALCAN database to analyze the expression of PXN in AML patients and its prognostic significance. Bone marrow samples of newly diagnosed AML patients were collected to extract RNA, and qRT-PCR was used to detect the expression of PXN . The prognosis was followed up. Chi-square test was used to analyze the relationship between PXN expression and clinical laboratory characteristics. Kaplan-Meier analysis was used to draw survival curve, and Cox regression analysis was used to analyze the independent factors affecting the prognosis of patients with AML. The co-expression genes of PXN were analyzed by LinkedOmics to explore its biological significance in AML. Results: Kaplan-Meier analysis showed that the overall survival time of AML patients was related to whether to receive treatment and PXN expression(P<0.05). COX regression analysis showed that whether to receive treatment (HR=0.227，95%CI=0.075-0.689， P =0.009) and high expression of PXN (HR=4.484，95%CI=1.449-13.889， P =0.009) were independent poor prognostic factors in patients with AML. Conclusion: PXN is highly expressed in AML patient, and high PXN expression is an indicator of poor prognosis in AML patient.

scholarly journals Identification of Seven Novel Ferroptosis-Related Long Non - Coding RNA Signatures as a Diagnostic Biomarker for Acute Myeloid Leukemia

2021 ◽  
Author(s):  
Zhiyuan Zheng ◽  
Wei Wu ◽  
Zehang Lin ◽  
Shuhan Liu ◽  
Qiaoqian Chen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Risk Score ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Kaplan Meier ◽  
Acute Myeloid

Abstract Background: Ferroptosis is a newly discovered type of programmed cell death that participates in the biological processes of various cancers. However, the mechanism by which ferroptosis modulates acute myeloid leukemia (AML) remains unclear. This study aimed to investigate the role of ferroptosis-related long non-coding RNAs (lncRNAs) in AML and establish a corresponding prognostic model.Methods: RNA-sequencing data and clinicopathological characteristics were obtained from The Cancer Genome Atlas database, and ferroptosis-related genes were obtained from the FerrDb database. The “limma” R package, Cox regression, and the least absolute shrinkage and selection operator were used to determine the ferroptosis-related lncRNA signature with the lowest Akaike information criteria (AIC). The risk score of ferroptosis-related lncRNAs was calculated and patients with AML were divided into high- and low-risk groups based on the median risk score. The Kaplan-Meier curve and Cox regression were used to evaluate the prognostic value of the risk score. Finally, gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the biological functions of the ferroptosis-related lncRNAs.Results: Seven ferroptosis-related lncRNA signatures were identified in the training group, and Kaplan-Meier and Cox regression analyses confirmed that risk scores were independent prognostic predictors of AML in both the training and validation groups (All P < 0.05). In addition, the area under the curve (AUC) analysis confirmed that the signatures had a good predictive ability for the prognosis of AML. GSEA and ssGSEA showed that the seven ferroptosis-related lncRNAs were related to glutathione metabolism and tumor immunity.Conclusions: In this study, seven novel ferroptosis-related lncRNA signatures (AP001266.2, AC133961.1, AF064858.3, AC007383.2, AC008906.1, AC026771.1, and KIF26B-AS1) were established. These signatures were shown to accurately predict the prognosis of AML, which would provide new insights into strategies for the development of new AML therapies.

scholarly journals The Construction and Exploration of the CeRNA Network and Patterns of Tumor-infiltrating Immune Cells in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Author(s):  
Weiwei Jia ◽  
Pengjia Li ◽  
Mingxia Ma ◽  
Xiaochen Niu ◽  
Lina Bai ◽  
...  
Keyword(s):  
T Cells ◽  
Regression Analysis ◽  
Mast Cells ◽  
Immune Cells ◽  
Prognostic Model ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Cerna Network ◽  
Follicular Helper ◽  
Lncrna Malat1

Abstract KIRC is the malignant tumor with the highest incidence and poor prognosis in renal cell carcinoma. We want to explore the possible mechanisms of KIRC and effective prognostic-related biomarkers. The sequencing information of 3 types of RNA (mRNA, lncRNA and miRNA) in 539 cases of KIRC tissues and 72 cases of normal tissues is obtained from the TCGA database. Methods such as univariate Cox regression analysis, lasso regression screening, and multivariate Cox regression analysis were used to construct a prognostic model based on the CeRNA network. There are 3074 mRNAs, 359 lncRNAs and 132 miRNAs differentially expressed that have been identified through differential analysis. A complete mRNA-miRNA-lncRNA (SIX1-hsa-miR-200b-3p-MALAT1) network was obtained based on the CeRNA network. The CIBERSORT algorithm was used to analyze the degree of infiltration of 22 kinds of immune cells from each sample of KIRC. Construction of a prognostic model based on tumor-infiltrating immune cells, 2 immune cells (Mast cells resting, T cells follicular helper) were identified by constructing a prognostic model. There was a negative correlation between lncRNA MALAT1 and Mast cells resting (R= -0.27, P < 0.001); while there was a positive correlation between lncRNA MALAT1 and T cells follicular helper (R = 0.23, P < 0.001).

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