scholarly journals N6-Methyladenosine-Regulated mRNAs: Potential Prognostic Biomarkers for Patients With Lung Adenocarcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Junjun Sun ◽  
Yili Ping ◽  
Jingjuan Huang ◽  
Bingjie Zeng ◽  
Ping Ji ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Mrna Expression ◽  
Cox Regression ◽  
Interaction Network ◽  
Prognostic Biomarkers ◽  
Cox Regression Analysis ◽  
Receiver Operating Characteristic Curves ◽  
Network Analyses ◽  
Kaplan Meier ◽  
Selection Operator

Aberrant regulation of m6A mRNA modification can lead to changes in gene expression, thus contributing to tumorigenesis in several types of solid tumors. In this study, by integrating analyses of m6A methylation and mRNA expression, we identified 84 m6A-regulated mRNAs in lung adenocarcinoma (LUAD). Although the m6A methylation levels of total RNA in LUAD patient tumor tissue were reduced, the majority (75.2%) of m6A-regulated mRNAs were hypermethylated. The m6A-hypermethylated mRNAs were mainly enriched in terms related to transcription factor activity. We established a 10-m6A-regulated-mRNA signature score system through least absolute shrinkage and selection operator Cox regression analysis, with its predictive value validated by Kaplan–Meier curve and time-dependent receiver operating characteristic curves. RFXAP and KHDRBS2 from the signature also exhibited an independent prognostic value. The co-expression and interaction network analyses demonstrated the strong correlation between m6A regulators and the genes in the signature, further supporting the results of the m6A methylation modification patterns. These findings highlight the potential utility of integrating multi-omics data (m6A methylation level and mRNA expression) to accurately obtain potential prognostic biomarkers, which may provide important insights into developing novel and effective therapies for LUAD.

scholarly journals Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Jianye Tan ◽  
Haofeng Liang ◽  
Bingsheng Yang ◽  
Shuang Zhu ◽  
Guofeng Wu ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Survival Rates ◽  
Prognostic Biomarkers ◽  
Messenger Rnas ◽  
Hub Genes ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Before And After

Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognostic genes were identified by performing univariate Cox regression analysis and the Kaplan–Meier (KM) survival analysis. We then examined the correlation between the expression level of prognostic lncRNAs and mRNAs. Furthermore, microRNAs (miRNAs) corresponding to the coexpression of lncRNA-mRNA was predicted, which was used to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, multivariate Cox proportional risk regression analysis was used to identify hub prognostic genes. Three hub prognostic genes (ABCG8, LOXL4, and PDE1B) were identified as potential prognostic biomarkers and therapeutic targets for OS. Furthermore, transcriptions factors (TFs) (DBP, ESX1, FOS, FOXI1, MEF2C, NFE2, and OTX2) and lncRNAs (RP11-357H14.16, RP11-284N8.3, and RP11-629G13.1) that were able to affect the expression levels of genes before and after transcription were found to regulate the prognostic hub genes. In addition, we identified drugs related to the prognostic hub genes, which may have potential clinical applications. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the expression levels of ABCG8, LOXL4, and PDE1B coincided with the results of bioinformatics analysis. Moreover, the relationship between the hub prognostic gene expression and patient prognosis was also validated. Our study elucidated the roles of three novel prognostic biomarkers in the pathogenesis of OS as well as presenting a potential clinical treatment for OS.

PPM1D is Associated With Prognosis of Bladder Cancer in the Chinese Population

2020 ◽  
Author(s):  
Shuangqing Cao ◽  
Lei Zheng
Keyword(s):  
Bladder Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Histological Grade ◽  
Tnm Stage ◽  
Cox Regression Analysis ◽  
Relative Expression ◽  
Kaplan Meier ◽  
Normal Bladder ◽  
Cancer Tissues

Abstract Background: Present study was to investigate the relative expression and prognostic performance of protein phosphatase magnesium/manganese-dependent 1D (PPM1D) in bladder cancer.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to examine the relative expression of PPM1D mRNA in bladder cancer tissues and adjacent normal bladder tissues. The associations of PPM1D mRNA expression with clinicopathological features and the prognostic value were statistically analyzed via Chi-square test, Kaplan-Meier method and Cox regression analysis.Results: In comparison to adjacent normal tissues, PPM1D mRNA expression was obviously increased in bladder cancer tissues (P<0.001). Abnormal PPM1D expression was remarkably related to histological grade (P=0.017), TNM stage (P=0.032) and lymph nodes metastasis (P=0.035). Kaplan-Meier method showed that a close relationship was found between PPM1D expression and overall survival time (P=0.000). Multivariate analysis indicated that PPM1D expression (P=0.000, HR=3.530, 95%CI: 2.001-6.228) was a promising independent predictor for the prognosis of bladder cancer patients, as well as TNM stage (P=0.042, HR=1.768, 95%CI: 1.021-3.062).Conclusion: Taken together, our data showed that the potential performance of PPM1D as a prognostic biomarker and therapeutic target of bladder cancer.

scholarly journals NUCKS1 Acts As A Promising Novel Bio-Marker in The Prognosis of Patients with Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Xianfeng Zhang ◽  
Xianjun Zhang ◽  
Xinguo Li ◽  
Hongbing Bao ◽  
Guang Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Prognostic Value ◽  
Cox Regression ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Kinase Substrate ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Relative Mrna Expression

Abstract Background: Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) was over-expressed in some tumors, including hepatocellular carcinoma (HCC). However, the clinical significance of NUCKS1 in HCC was still unclear. The aim of this study was to explore the expression and prognostic value of NUCKS1 in HCC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of NUCKS1 in HCC tissues and corresponding adjacent normal tissues. The relationship between NUCKS1 expression and clinical characteristics of patients was analyzed by c2 test. Kaplan-Meier method and cox regression analysis were applied to estimate the prognostic value of NUCKS1 in HCC. Results: Compared with normal tissues, the relative mRNA expression level of NUCKS1 was significantly up-regulated in HCC tissues (P < 0.001). And high NUCKS1 expression was closely associated with tumor differentiation, TNM stage, vascular invasion and metastasis (P < 0.05). Kaplan-Meier analysis revealed that the overall survival of HCC patients with low expression of NUCKS1 was obviously longer than those with high NUCKS1 expression (log rank test, P = 0.001). NUCKS1 was an independent prognostic factor of HCC patients via univariate and multivariate cox regression analyses.Conclusions: NUCKS1 may be correlated with the progression of HCC and may serve as a potential factor for the prognosis of this disease.

scholarly journals Lepidic component identifies a subgroup of lung adenocarcinoma with a distinctive prognosis: a multicenter propensity-matched analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592098284
Author(s):  
Erjia Zhu ◽  
Chenyang Dai ◽  
Huikang Xie ◽  
Hang Su ◽  
Xuefei Hu ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Survival Rates ◽  
Prognostic Impact ◽  
Data Set ◽  
Cox Regression Analysis ◽  
T Stage ◽  
Kaplan Meier ◽  
T Classification

Background: Our aim was to investigate the prognostic impact of the lepidic component on T stage in patients with lung adenocarcinoma (LUAD). Methods: A retrospective data set including 863 cases of LUAD with lepidic component and 856 cases without lepidic component was used to identify matched lepidic-positive and lepidic-negative cohorts ( n = 376 patients per group) using a propensity-score matching. Primary outcome variables included recurrence-free survival (RFS) and overall survival (OS). Prognostic factors were assessed by Cox regression analysis and Kaplan–Meier estimates. Results: Multivariate analysis revealed that lepidic component presence was an independent prognostic factor for prolonged RFS ( p < 0.001) and OS ( p < 0.001). Furthermore, lepidic ratio (LR) >25% or ⩽25% were confirmed to be independent prolonged survival predictors. No survival differences were observed between patients with LUAD with LR >25% or ⩽25% (RFS p = 0.333; OS p = 0.078). The 5-year OS rates of patients with LUAD with a lepidic component were 90% regardless of the T stage, and these survival rates were significantly better than those of patients with LUAD without a lepidic component in the corresponding T stage. Multivariate analysis confirmed that T stage was associated with survival only in patients with LUAD without a lepidic component. Conclusions: Lepidic component presence identifies a LUAD subgroup with an excellent prognosis independent of the LR, pathological T classification. Considering the lepidic component presence may improve prognostic predictions for patients with LUAD.

scholarly journals Expression Status and Prognostic Value of m6A RNA Methylation Regulators in Lung Adenocarcinoma

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 619
Author(s):  
Xiuhong Li ◽  
Zian Feng ◽  
Rui Wang ◽  
Jie Hu ◽  
Xiaodong He ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Survival Analysis ◽  
Lung Adenocarcinoma ◽  
Roc Curve ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Rna Methylation ◽  
Kaplan Meier ◽  
M6a Rna Methylation ◽  
Prediction Efficiency

N6-methyladenosine (m6A) RNA modification is the most abundant modification method in mRNA, and it plays an important role in the occurrence and development of many cancers. This paper mainly discusses the role of m6A RNA methylation regulators in lung adenocarcinoma (LUAD) to identify novel prognostic biomarkers. The gene expression data of 19 m6A methylation regulators in LUAD patients and its relevant clinical parameters were extracted from The Cancer Genome Atlas (TCGA) database. We selected three significantly differentially expressed m6A regulators in LUAD to construct the risk signature, and evaluated its prognostic prediction efficiency using the receiver operating characteristic (ROC) curve. Kaplan–Meier survival analysis and Cox regression analysis were used to identify the independent prognostic significance of the risk signature. The ROC curve indicated that the area under the curve (AUC) was 0.659, which means that the risk signature had a good prediction efficiency. The results of the Kaplan–Meier survival analysis and Cox regression analysis showed that the risk score can be used as an independent prognostic factor for LUAD. In addition, we explored the differential signaling pathways and cellular processes related to m6A methylation regulators in LUAD.

scholarly journals The correlation of WDR76 expression with survival outcomes and immune infiltrates in lung adenocarcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12277
Author(s):  
Likui Fang ◽  
Guocan Yu ◽  
Wenfeng Yu ◽  
Gang Chen ◽  
Bo Ye
Keyword(s):  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Interaction Network ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Survival Outcomes ◽  
Clinicopathologic Characteristics ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
The Impact

Background WD repeat domain 76 (WDR76) is a predicted member of the WD40-repeat-containing domain superfamily and possibly involves in various biological processes, but its function in cancers is poorly characterized. This study aimed to evaluate the role of WDR76 in the prognosis and immune infiltrates of lung adenocarcinoma (LUAD). Methods WDR76 expressions in LUAD tissues and normal tissues were primarily compared by The Cancer Genome Atlas (TCGA) database, and were validated in cohorts from Gene Expression Omnibus (GEO) database. The associations between WDR76 expression and clinicopathologic characteristics were analyzed. Kaplan–Meier and Cox regression analyses were performed to determine the impact of WDR76 expression on survival outcomes. The protein interaction network of WDR76 was built using STRING website. TIMER and GEPIA databases were used to investigate the correlation between WDR76 expression and immune infiltrates. Results WDR76 expression was elevated in LUAD (P < 0.001) and high WDR76 expression was associated with advanced N stage, M stage and pathologic stage. Expectedly, high WDR76 expression significantly correlated with poor survival outcomes and was the independent risk factor for overall survival (OS) (HR 1.468, 95% CI [1.031–2.089], P = 0.033) and disease specific survival (DSS) (HR 1.764, 95% CI [1.095–2.842], P = 0.020). DDB1 and LSH were the important proteins interacting with WDR76. WDR76 expression correlated with CD8+ T cells presence and was also positively associated with levels of inhibitory receptors. Conclusion WDR76 expression was involved in the regulation of immune infiltrates and had predictive value for prognosis in LUAD.

scholarly journals Establishment of a 5 DNA Methylation Site Prognostic Signature Associated with N6-Methyladenosine in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Liqiang Yuan ◽  
Wei Jiang ◽  
Zhanyu Xu ◽  
Kung Deng ◽  
Yu Sun ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Clinicopathological Parameters ◽  
Main Body ◽  
Methylation Site ◽  
Cox Regression Analysis ◽  
Site Model ◽  
Kaplan Meier ◽  
Cox Analysis

Abstract Background: There is a high incidence of lung adenocarcinoma (LUAD). Even with surgery, targeted therapy and immunotherapy, the survival rate of LUAD patients is still low. N6-methyladenosine (m6A) and DNA methylation markers can help with the diagnosis and treatment of LUAD patients. Therefore, it is necessary to identify a novel m6A-related DNA methylation sites signature to predict the survival of patients with LUAD. Methods: In this study, we screened 15 m6A-related genes and their 217 methylation sites. RNA sequencing data of 15 genes and the clinicopathological parameters of TCGA-LUAD were obtained from the TCGA database (http://cancergenome.nih.gov/). The LUAD-DNA CpG site information was obtained from the Illumina Human Methylation 450 BeadChip (Illumina, San Diego, CA, United States). The methylation sites related to prognosis were screened using univariate COX analysis, and the independent predictors of LUAD patients were identified using multivariate COX analysis of least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Finally, a model with 5 methylation sites as the main body to predict the prognosis of OS in patients with LUAD was obtained. According to the risk grouping of the prediction model, Kaplan-Meier curve and the receiver operating characteristic (ROC) curve were performed in the test and training sets to assess the predicted capacity of the model. In addition, a nomogram constructed by combining the risk score of methylation group and other related clinicopathological factors to verify the reliability of our model.Results: We constructed a m6A-related 5-DNA methylation site model to predict OS in LUAD patients. According to the results of the Kaplan-Meier curve, both the test set and the training set, the high-risk group showed a worse prognosis. The AUCs of the 5 DNA methylation signature at 1, 5 and 10 years in test datasets were 0.730, 0.649 and 0.726, respectively, and 0.679, 0.656 and 0.732 in training datasets. Finally, we constructed a nomogram to further verify the reliability of the model.Conclusion: In this study, we analyzed the methylation sites of m6A-related genes and established a m6A-related 5-DNA methylation site model to predict OS in LUAD patients.

scholarly journals Methylation and transcriptome analysis reveal lung adenocarcinoma-specific diagnostic biomarkers

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Rui Li ◽  
Yi-E Yang ◽  
Yun-Hong Yin ◽  
Meng-Yu Zhang ◽  
Hao Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
R Package ◽  
Functional Enrichment ◽  
Independent Effect ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Differentially Methylated Genes

Abstract Background DNA methylation can regulate the role of long noncoding RNAs (lncRNAs) in the development of lung adenocarcinoma (LUAD). The present study aimed to identify methylation-driven lncRNAs and mRNAs as biomarkers in the prognosis of LUAD using bioinformatics analysis. Methods Differentially expressed RNAs were obtained using the edge R package from 535 LUAD tissues and 59 adjacent non-LUAD tissues. Differentially methylated genes were obtained using the limma R package from 475 LUAD tissues and 32 adjacent non-LUAD tissues. Methylation-driven mRNA and lncRNA were obtained using the MethylMix R package from 465 LUAD tissues with matched DNA methylation and RNA expression and 32 non-LUAD tissues with DNA methylation. Gene ontology and ConsensusPathDB pathway analysis were performed to identify functional enrichment of methylation-driven mRNAs. Univariate and multivariate Cox regression analyses were performed to identify the independent effect of each variable for predicting the prognosis of LUAD. Kaplan–Meier curve analysis of DNA methylation and gene expression might provide potential prognostic biomarkers for LUAD patients. Results A total of 99 methylation-driven mRNAs and 17 methylation-driven lncRNAs were obtained. Univariate and multivariate Cox regression analysis showed that 6 lncRNAs (FOXE1, HOXB13-AS1_2, VMO1, HIST1H3F, AJ003147.8, ASXL3) were retrieved to construct a predictive model associated with overall survival in LUAD patients. Combined DNA methylation and gene expression survival analysis revealed that 4 lncRNAs (AC023824.1, AF186192.1, LINC01354 and WASIR2) and 8 mRNAs (S1PR1, CCDC181, F2RL1, EFS, KLHDC9, MPV17L, GKN2, ITPRIPL1) might act as independent biomarkers for the prognosis of LUAD. Conclusions Methylation-driven lncRNA and mRNA contribute to the survival of LUAD, and 4 lncRNAs and 8 mRNAs might be potential biomarkers for the prognosis of LUAD.

scholarly journals Identification and Validation of a Ferroptosis-Related Long Non-coding RNA Signature for Predicting the Outcome of Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhiyuan Zheng ◽  
Qian Zhang ◽  
Wei Wu ◽  
Yan Xue ◽  
Shuhan Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Information Criteria ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Regression Analyses ◽  
Cox Regression Analysis ◽  
Kaplan Meier

BackgroundFerroptosis is a recently recognized type of programmed cell death that is involved in the biological processes of various cancers. However, the mechanism of ferroptosis in lung adenocarcinoma (LUAD) remains unclear. This study aimed to determine the role of ferroptosis-associated long non-coding RNAs (lncRNAs) in LUAD and to establish a prognostic model.MethodsWe downloaded ferroptosis-related genes from the FerrDb database and RNA sequencing data and clinicopathological characteristics from The Cancer Genome Atlas. We randomly divided the data into training and validation sets. Ferroptosis-associated lncRNA signatures with the lowest Akaike information criteria were determined using COX regression analysis and the least absolute shrinkage and selection operator. The risk scores of ferroptosis-related lncRNAs were calculated, and patients with LUAD were assigned to high- and low-risk groups based on the median risk score. The prognostic value of the risk scores was evaluated using Kaplan–Meier curves, Cox regression analyses, and nomograms. We then explored relationships between ferroptosis-related lncRNAs and the immune response using gene set enrichment analysis (GSEA).ResultsTen ferroptosis-related lncRNA signatures were identified in the training group, and Kaplan–Meier and Cox regression analyses confirmed that the risk scores were independent predictors of LUAD outcome in the training and validation sets (all P &lt; 0.05). The area under the curve confirmed that the signatures could determine the prognosis of LUAD. The predictive accuracy of the established nomogram model was verified using the concordance index and calibration curve. The GSEA showed that the 10 ferroptosis-related lncRNAs might be associated with tumor immune response.ConclusionWe established a novel signature involving 10 ferroptosis-related lncRNAs (LINC01843, MIR193BHG, AC091185.1, AC027031.2, AL021707.2, AL031667.3, AL606834.1, AC026355.1, AC124045.1, and AC025048.4) that can accurately predict the outcome of LUAD and are associated with the immune response. This will provide new insights into the development of new therapies for LUAD.

scholarly journals WISP1 and miR-29c-3p are novel prognostic biomarkers and therapeutic targets for bladder cancer

2021 ◽  
Author(s):  
Lihua Zhang ◽  
Zhuo Wang ◽  
Hongyi Zhou ◽  
Ming Zhu ◽  
Leilei Zhu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Tumor Size ◽  
In Silico ◽  
Cox Regression ◽  
Therapeutic Targets ◽  
Prognostic Biomarkers ◽  
Aberrant Expression ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Abstract Background: Aberrant expression of WISP1 is associated with carcinogenesis; however, the expression and prognostic values of WISP1 in bladder cancer (BC) remain elusive. Therefore, the present study aimed to investigate the WISP1 expression in BC and explore the possible mechanisms and clinical value of WISP1 in BC. Methods: The in silico analysis based on oncomine and Kaplan-Meier Plotter databases were to reveal WISP1 expression and prognosis in BC. Besides, qRT-PCR, immunohistochemistry (IHC) and western blot assays were used to detect WISP1 expression both in BC tissues and BC cell lines. TargetScan database was used to predict miRNAs that putatively regulate the expression of WISP1. COX regression and the Kaplan-Meier method were applied to evaluate the prognostic value of WISP1 and miRNAs in BC.Results: WISP1 was up-regulated in BC and associated with poor survival in patients with BC through in silico analysis. Besides, WISP1 expression was identified to be up-regulated both in BC tissues and cell lines. We identified 13 miRNAs that putatively regulate the expression of WISP1. Of these miRNAs, only miR-29c-3p was found to be significantly negatively correlated with WISP1 in BC tissues. The correlation of in situ expressions of WISP1 and miR-29c-3p by immunohistochemistry (IHC) and clinical characteristics revealed that WISP1 was significantly associated with tumor size and hsa-miR-23b-3p expression, and miR-29c-3p was associated with tumor size, M stage, and WISP1 expression. Multivariate Cox regression analysis indicated that TNM stage and WISP1 expression were predictors of unfavorable prognosis, while hsa-miR-29c-3p was a predictor of favorable prognosis in patients with BC. Conclusions: Collectively, the findings indicated that WISP1 and miR-29c-3p might serve as novel prognostic biomarkers and potential therapeutic targets for BC.

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