scholarly journals Derivation and Comprehensive Analysis of Aging Patterns in Patients with Bladder Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Bin Wang ◽  
Fachun Tong ◽  
Chengxi Zhai ◽  
Long Wang ◽  
Yunzan Liu ◽  
...  

Background. Aging is an essential risk factor for cancer. However, aging-related genes (ARGs) have not been comprehensively analyzed in bladder cancer (BC). Therefore, the study is aimed at derivating a risk stratification system for BC patients based on ARGs. Methods. Public databases were used to acquire ARGs sets, transcriptome files, and clinical data. The “limma” package was then used to screen for differential ARGs while also using univariate Cox regression analysis to explore for prognostic ARGs. The “ConsensusClusterPlus” package was used to perform aging patterns in BC patients based on the above prognostic ARGs. Subsequently, aging patterns were investigated in survival prediction, mutation landscape, immunotherapy, immunological checkpoints, and immune microenvironment. We likewise utilized gene enrichment analysis to explore the biological functions that were behind the findings. To construct a risk signature and nonogram for prognostic prediction, we used LASSO and Cox regression analysis based on differential genes in aging patterns. In addition, we plotted a nomogram and validate the accuracy of the risk signature in GEO and TCGA cohorts. We explored the possible biological mechanism using GSEA analysis and preliminarily identified a hub gene using PPI network. Finally, we validated the expression of hub gene in BC cell lines. Results. We screened 84 downregulated ARGs, 74 upregulated ARGs, and 32 prognostic ARGs in the human aging genome resource. The aging patterns based on prognostic genes had excellent survival prediction ( p < 0.001 ) and discriminatory ability in 405 BC patients. In addition, we found no significant differences in aging patterns in mutation analysis, which were all characterized by TP53, TTN, and KMT2D mutations. It is worth noting that cluster B in the aging patterns has a better response to immunotherapy and a more active immune microenvironment ( p < 0.05 ). In addition, gene enrichment analysis showed that aging patterns may be related to biological processes such as Staphylococcus aureus infection, phagosome, and cytokine-cytokine receptor interaction. Subsequently, we constructed a risk signature based on 16 differential genes from different aging patterns and had good survival prediction ability in both GEO and TCGA cohort. Specifically, survival analysis revealed a significantly shorter survival time in the high-risk group than in the low-risk group (TCGA and GEO, p < 0.001 ). In addition, AUC values in the ROC analysis predicted 1, 3, and 5 years in TCGA cohort that are 0.713, 0.714, and 0.738, respectively. AUC values predicted 1, 3, and 5 years in GEO cohort that are 0.606, 0.663, and 0.718, respectively. There is no doubt that risk score was an independent prognostic factor from results of multivariate Cox regression analysis in BC patients ( p < 0.001 ). There were also significant differences in immune cell infiltration, immune checkpoint, and immune score between the two groups ( p < 0.05 ), but it should not be ignored that the correlation with the HLA expression was weak. Finally, we identified and validated CLIC3 as a hub gene that may be involved in the Wnt signaling pathway, etc. Conclusion. We provided robust evidences that aging patterns based on ARGs can guide targeted therapy and survival prediction in BC patients.

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Rui Wang ◽  
Wenxuan Bu ◽  
Yang Yang

Multiple myeloma (MM) is the second most commonly diagnosed hematological malignancy. Understanding the basic mechanisms of the metabolism in MM may lead to new therapies that benefit patients. We collected the gene expression profile data of GSE39754 and performed differential analysis. Furthermore, identify the candidate genes that affect the prognosis of the differentially expressed genes (DEGs) related to the metabolism. Enrichment analysis is used to identify the biological effects of candidate genes. Perform coexpression analysis on the verified DEGs. In addition, the candidate genes are used to cluster MM into different subtypes through consistent clustering. Use LASSO regression analysis to identify key genes, and use Cox regression analysis to evaluate the prognostic effects of key genes. Evaluation of immune cell infiltration in MM is by CIBERSORT. We identified 2821 DEGs, of which 348 genes were metabolic-related prognostic genes and were considered candidate genes. Enrichment analysis revealed that the candidate genes are mainly related to the proteasome, purine metabolism, and cysteine and methionine metabolism signaling pathways. According to the consensus clustering method, we identified the two subtypes of group 1 and group 2 that affect the prognosis of MM patients. Using the LASSO model, we have identified 10 key genes. The prognosis of the high-risk group identified by Cox regression analysis is worse than that of the low-risk group. Among them, PKLR has a greater impact on the prognosis of MM, and the prognosis of MM patients is poor when the expression is high. In addition, the level of immune cell infiltration in the high-risk group is higher than that in the low-risk group. In the summary, metabolism-related genes significantly affect the prognosis of MM patients through the metabolic process of MM patients. PKLR may be a prognostic risk factor for MM patients.


2021 ◽  
Vol 8 ◽  
Author(s):  
Ji Yin ◽  
Xiaohui Li ◽  
Caifeng Lv ◽  
Xian He ◽  
Xiaoqin Luo ◽  
...  

Background: Long non-coding RNA (lncRNA) plays a significant role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). This article aims to develop an immune-related lncRNA (irlncRNA) model, regardless of expression levels, for risk assessment and prognosis prediction in HNSCC patients.Methods: We obtained clinical data and corresponding full transcriptome expression of HNSCC patients from TCGA, downloaded GTF files to distinguish lncRNAs from Ensembl, discerned irlncRNAs based on co-expression analysis, distinguished differentially expressed irlncRNAs (DEirlncRNAs), and paired these DEirlncRNAs. Univariate Cox regression analysis, LASSO regression analysis, and stepwise multivariate Cox regression analysis were then performed to screen lncRNA pairs, calculate the risk coefficient, and establish a prognosis model. Finally, the predictive power of this model was validated through the AUC and the ROC curves, and the AIC values of each point on the five-year ROC curve were calculated to select the maximum inflection point, which was applied as a cut-off point to divide patients into low- or high-risk groups. Based on this methodology, we were able to more effectively differentiate between these groups in terms of survival, clinico-pathological characteristics, tumor immune infiltrating status, chemotherapeutics sensitivity, and immunosuppressive molecules.Results: A 13-irlncRNA-pair signature was built, and the ROC analysis demonstrated high sensitivity and specificity of this signature for survival prediction. The Kaplan–Meier analysis indicated that the high-risk group had a significantly shorter survival rate than the low-risk group, and the chi-squared test certified that the signature was highly related to survival status, clinical stage, T stage, and N stage. Additionally, the signature was further proven to be an independent prognostic risk factor via the Cox regression analyses, and immune infiltrating analyses showed that the high-risk group had significant negative relationships with various immune infiltrations. Finally, the chemotherapeutics sensitivity and the expression level of molecular markers were also significantly different between high- and low-risk groups.Conclusion: The signature established by paring irlncRNAs, with regard to specific expression levels, can be utilized for survival prediction and to guide clinical therapy in HNSCC.


2021 ◽  
Author(s):  
Zhian Ling ◽  
Yuting Liang ◽  
Suping Wei ◽  
Yuanming Chen ◽  
Jinmin Zhao

Abstract Background N6-methylandenosine (m6A) methylation is one of the most common methylation modifications in RNA. At present, a large number of studies have found that m6A methylation can regulate the occurrence and development of tumors by modifying mRNA. However, it is still unclear how m6A modifies Long non-coding RNA (lncRNA) that regulates mRNA expression by interacting with miRNA to affect the occurrence and development of osteosarcoma(OS). Therefore, exploring the lncRNAs related to m6A methylation and identifying lncRNAs that have both prognostic effects and immune functions are things that need to be solved urgently. Methods The published gene expression data of OS and complete clinical annotation files were obtained from the TARGET database. LncRNAs with P <0.001 from the results of Pearson correlation coefficient analysis as m6A-related lncRNAs were screened. Single-factor Cox regression analysis was used to screening prognostic- related lncRNA combined with the clinical information of patients and constructed a prognostic model based on lasso regression analysis. Then we explored the differences in survival and immune function of different subtypes that be obtained using the Consensus Cluster. The enrichment of differential genes between high and low risk groups in the KEGG pathway is achieved through Gene set enrichment analysis(GSEA). Results We obtained 706 lncRNAs in the TARGET database. Consensus clustering method were used to divide patients with OS into subgroups based on the expression of 26 prognostic-related lncRNAs. Through Kaplan-Meier survival analysis, there are significant differences between the two subgroups. The average immune score (P = 0.02), stromal score(P =0.027), and estimate score༈P = 0.015༉were higher in cluster 1 than in cluster 2. We found that compared with cluster 2, SIGLEC15, HAVCR2, LAG3, and PDCD1 were highly expressed in cluster 1.We obtain a prognostic model by lasso regression analysis. In the training group and the text group, the OS curve showed that patients in the high-risk group had a poorer prognosis than those in the low-risk group. In the training set, univariate Cox regression analysis and multivariate Cox regression analysis showed that the risk score was correlated with the prognosis of OS patients. In the high-risk group, the Linoleic acid metabolism and the Glycine, serine and threonine metabolism pathway were mainly involved by Gene Set Enrichment analysis. The abundance of Mast cells activated (P ≦0.024) and T cells CD4 (P ≦0.0044) naive were positively association the risk score. Conclusions This study clarified the important role of m6A-related lncRNAs in the prognosis and immune microenvironment of patients with OS, and indicate that m6A-related prognostic lncRNA signals may provide new targets for the diagnosis and treatment of OS.


2021 ◽  
Author(s):  
Hongyang Liu ◽  
Junhu Wan ◽  
Quanling Feng ◽  
Jingyu Li ◽  
Jun Liu ◽  
...  

Abstract Background: Endometrial cancer (EC) is one of the most common types of gynecological cancer. Hypoxia is an important clinical feature and regulates various tumor processes. However, the prognostic value of hypoxia-related lncRNA in EC remains to be further elucidated. Here, we aimed to characterize the molecular features of EC by the development of a classification system based on the expression profile of hypoxia-related lncRNA.Methods: Univariate Cox regression analysis was used to identify hypoxia-related lncRNAs associated with overall survival. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct gene signature. Multivariate Cox regression analysis and receiver operating characteristic (ROC) curve analysis were also performed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEEG) pathway, and Gene Set Enrichment Analysis (GESA) were used to identify hypoxia-related lncRNA pathway. Western blot and real-time PCR were used to detect target gene expression. The cell proliferation was determined by using WST-1 assay.Results: Based on univariate Cox regression analysis, we identified 17 hypoxia-related lncRNAs significantly associated with overall survival. Next, the least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature in the TCGA EC cohort. The risk score was confirmed as an independent predictor for overall survival in multivariate Cox regression analysis and receiver operating characteristic (ROC) curve analysis. Besides, the survival time of EC patients in different risk group was significantly correlated to clinicopathologic factors, such as age, stage and grade. Furthermore, hypoxia-related lncRNA associated with the high-risk group were involved in various aspects of the malignant progression of EC via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEEG) pathway, and Gene Set Enrichment Analysis (GESA). Besides, using CIBERSORT analysis, we found a different immune cell environment characterization of EC between different cluster and risk group. Moreover, the risk score was closely correlated to immunotherapy response, microsatellite instability and tumor mutation burden (TMB). Finally, we select one hypoxia-related lncRNA SOS1-IT1 to validate its role in hypoxia and EC progression. Interestingly, we found SOS1-IT1 was overexpressed in tumor tissues, and closely correlated with clinicopathological parameters of EC. The expression level of SOS1-IT1 was significantly increased under hypoxia condition. Additionally, the important hypoxia regulatory factor HIF-1α can directly bind SOS1-IT1 promoter region, and affect its expression level. Conclusions: In summary, this study established a new EC classification based on the hypoxia-related lncRNA signature, thereby provide a novel sight to understand the potential mechanism of human EC development.


2021 ◽  
Author(s):  
Yan Li ◽  
Xiaoying Wang ◽  
Yue Han ◽  
Xun Li

Abstract Background: Long non-coding RNAs (lncRNAs) play an important role in angiogenesis, immune response, inflammatory response and tumor development and metastasis. m6 A (N6 - methyladenosine) is one of the most common RNA modifications in eukaryotes. The aim of our research was to investigate the potential prognostic value of m6A-related lncRNAs in ovarian cancer (OC).Methods: The data we need for our research was downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Pearson correlation analysis between 21 m6A regulators and lncRNAs was performed to identify m6A-related lncRNAs. Univariate Cox regression analysis was implemented to screen for lncRNAs with prognostic value. A least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analyses was used to further reduct the lncRNAs with prognostic value and construct a m6A-related lncRNAs signature for predicting the prognosis of OC patients. Results: 275 m6A-related lncRNAs were obtained using pearson correlation analysis. 29 m6A-related lncRNAs with prognostic value was selected through univariate Cox regression analysis. Then, a seven m6A-related lncRNAs signature was identified by LASSO Cox regression. Each patient obtained a riskscore through multivariate Cox regression analyses and the patients were classified into high-and low-risk group using the median riskscore as a cutoff. Kaplan-Meier curve revealed that the patients in high-risk group have poor outcome. The receiver operating characteristic curve revealed that the predictive potential of the m6A-related lncRNAs signature for OC was powerful. The predictive potential of the m6A-related lncRNAs signature was successfully validated in the GSE9891, GSE26193 datasets and our clinical specimens. Multivariate analyses suggested that the m6A-related lncRNAs signature was an independent prognostic factor for OC patients. Moreover, a nomogram based on the expression level of the seven m6A-related lncRNAs was established to predict survival rate of patients with OC. Finally, a competing endogenous RNA (ceRNA) network associated with the seven m6A-related lncRNAs was constructed to understand the possible mechanisms of the m6A-related lncRNAs involed in the progression of OC.Conclusions: In conclusion, our research revealed that the m6A-related lncRNAs may affect the prognosis of OC patients and identified a seven m6A-related lncRNAs signature to predict the prognosis of OC patients.


2021 ◽  
Author(s):  
Shaopei Ye ◽  
Wenbin Tang ◽  
Ke Huang

Abstract Background: Autophagy is a biological process to eliminate dysfunctional organelles, aggregates or even long-lived proteins. . Nevertheless, the potential function and prognostic values of autophagy in Wilms Tumor (WT) are complex and remain to be clarifed. Therefore, we proposed to systematically examine the roles of autophagy-associated genes (ARGs) in WT.Methods: Here, we obtained differentially expressed autophagy-related genes (ARGs) between healthy and Wilms tumor from Therapeutically Applicable Research To Generate Effective Treatments(TARGET) and The Cancer Genome Atlas (TCGA) database. The functionalities of the differentially expressed ARGs were analyzed using Gene Ontology. Then univariate COX regression analysis and multivariate COX regression analysis were performed to acquire nine autophagy genes related to WT patients’ survival. According to the risk score, the patients were divided into high-risk and low-risk groups. The Kaplan-Meier curve demonstrated that patients with a high-risk score tend to have a poor prognosis.Results: Eighteen DEARGs were identifed, and nine ARGs were fnally utilized to establish the FAGs based signature in the TCGA cohort. we found that patients in the high-risk group were associated with mutations in TP53. We further conducted CIBERSORT analysis, and found that the infiltration of Macrophage M1 was increased in the high-risk group. Finally, the expression levels of crucial ARGs were verifed by the experiment, which were consistent with our bioinformatics analysis.Conclusions: we emphasized the clinical significance of autophagy in WT, established a prediction system based on autophagy, and identified a promising therapeutic target of autophagy for WT.


2021 ◽  
Vol 20 ◽  
pp. 153303382110414
Author(s):  
Xiaoyong Li ◽  
Jiaqong Lin ◽  
Yuguo pan ◽  
Peng Cui ◽  
Jintang Xia

Background: Liver progenitor cells (LPCs) play significant roles in the development and progression of hepatocellular carcinoma (HCC). However, no studies on the value of LPC-related genes for evaluating HCC prognosis exist. We developed a gene signature of LPC-related genes for prognostication in HCC. Methods: To identify LPC-related genes, we analyzed mRNA expression arrays from a dataset (GSE57812 & GSE 37071) containing LPCs, mature hepatocytes, and embryonic stem cell samples. HCC RNA-Seq data from The Cancer Genome Atlas (TCGA) were used to explore the differentially expressed genes (DEGs) related to prognosis through DEG analysis and univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed to construct the LPC-related gene prognostic model in the TCGA training dataset. This model was validated in the TCGA testing set and an external dataset (International Cancer Genome Consortium [ICGC] dataset). Finally, we investigated the relationship between this prognostic model with tumor-node-metastasis stage, tumor grade, and vascular invasion of HCC. Results: Overall, 1770 genes were identified as LPC-related genes, of which 92 genes were identified as DEGs in HCC tissues compared with normal tissues. Furthermore, we randomly assigned patients from the TCGA dataset to the training and testing cohorts. Twenty-six DEGs correlated with overall survival (OS) in the univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed in the TCGA training set, and a 3-gene signature was constructed to stratify patients into 2 risk groups: high-risk and low-risk. Patients in the high-risk group had significantly lower OS than those in the low-risk group. Receiver operating characteristic curve analysis confirmed the signature's predictive capacity. Moreover, the risk score was confirmed to be an independent predictor for patients with HCC. Conclusion: We demonstrated that the LPC-related gene signature can be used for prognostication in HCC. Thus, targeting LPCs may serve as a therapeutic alternative for HCC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guomin Wu ◽  
Qihao Wang ◽  
Ting Zhu ◽  
Linhai Fu ◽  
Zhupeng Li ◽  
...  

This study aimed to establish a prognostic risk model for lung adenocarcinoma (LUAD). We firstly divided 535 LUAD samples in TCGA-LUAD into high-, medium-, and low-immune infiltration groups by consensus clustering analysis according to immunological competence assessment by single-sample gene set enrichment analysis (ssGSEA). Profile of long non-coding RNAs (lncRNAs) in normal samples and LUAD samples in TCGA was used for a differential expression analysis in the high- and low-immune infiltration groups. A total of 1,570 immune-related differential lncRNAs in LUAD were obtained by intersecting the above results. Afterward, univariate COX regression analysis and multivariate stepwise COX regression analysis were conducted to screen prognosis-related lncRNAs, and an eight-immune-related-lncRNA prognostic signature was finally acquired (AL365181.2, AC012213.4, DRAIC, MRGPRG-AS1, AP002478.1, AC092168.2, FAM30A, and LINC02412). Kaplan–Meier analysis and ROC analysis indicated that the eight-lncRNA-based model was accurate to predict the prognosis of LUAD patients. Simultaneously, univariate COX regression analysis and multivariate COX regression analysis were undertaken on clinical features and risk scores. It was illustrated that the risk score was a prognostic factor independent from clinical features. Moreover, immune data of LUAD in the TIMER database were analyzed. The eight-immune-related-lncRNA prognostic signature was related to the infiltration of B cells, CD4+ T cells, and dendritic cells. GSEA enrichment analysis revealed significant differences in high- and low-risk groups in pathways like pentose phosphate pathway, ubiquitin mediated proteolysis, and P53 signaling pathway. This study helps to treat LUAD patients and explore molecules related to LUAD immune infiltration to deeply understand the specific mechanism.


2021 ◽  
Author(s):  
Sijia Li ◽  
Hongyang Zhang ◽  
Wei Li

Abstract Background: The purpose of our study is establishing a model based on ferroptosis-related genes predicting the prognosis of patients with head and neck squamous cell carcinoma (HNSCC).Methods: In our study, transcriptome and clinical data of HNSCC patients were from The Cancer Genome Atlas, ferroptosis-related genes and pathways were from Ferroptosis Signatures Database. Differentially expressed genes (DEGs) were screened by comparing tumor and adjacent normal tissues. Functional enrichment analysis of DEGs, protein-protein interaction network and gene mutation examination were applied. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression were used to identified DEGs. The model was constructed by multivariate Cox regression analysis and verified by Kaplan-Meier analysis. The relationship between risk scores and other clinical features was also analyzed. Univariate and multivariate Cox analysis was used to verified the independence of our model. The model was evaluated by receiver operating characteristic analysis and calculation of the area under the curve (AUC). A nomogram model based on risk score, age, gender and TNM stages was constructed.Results: We analyzed data including 500 tumor tissues and 44 adjacent normal tissues and 259 ferroptosis-related genes, then obtained 73 DEGs. Univariate Cox regression analysis screened out 16 genes related to overall survival, and LASSO analysis fingered out 12 of them with prognostic value. A risk score model based on these 12 genes was constructed by multivariate Cox regression analysis. According to the median risk score, patients were divided into high-risk group and low-risk group. The survival rate of high-risk group was significantly lower than that of low-risk group in Kaplan-Meier curve. Risk scores were related to T and grade. Univariate and multivariate Cox analysis showed our model was an independent prognostic factor. The AUC was 0.669. The nomogram showed high accuracy predicting the prognosis of HNSCC patients.Conclusion: Our model based on 12 ferroptosis-related genes performed excellently in predicting the prognosis of HNSCC patients. Ferroptosis-related genes may be promising biomarkers for HNSCC treatment and prognosis.


2021 ◽  
Vol 16 ◽  
Author(s):  
Dongqing Su ◽  
Qianzi Lu ◽  
Yi Pan ◽  
Yao Yu ◽  
Shiyuan Wang ◽  
...  

Background: Breast cancer has plagued women for many years and caused many deaths around the world. Method: In this study, based on the weighted correlation network analysis, univariate Cox regression analysis and least absolute shrinkage and selection operator, 12 immune-related genes were selected to construct the risk score for breast cancer patients. The multivariable Cox regression analysis, gene set enrichment analysis and nomogram were also conducted in this study. Results: Good results were obtained in the survival analysis, enrichment analysis, multivariable Cox regression analysis and immune-related feature analysis. When the risk score model was applied in 22 breast cancer cohorts, the univariate Cox regression analysis demonstrated that the risk score model was significantly associated with overall survival in most of the breast cancer cohorts. Conclusion: Based on these results, we could conclude that the proposed risk score model may be a promising method, and may improve the treatment stratification of breast cancer patients in the future work.


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