scholarly journals Identification Sixteen Metabolic Genes as Potential Biomarkers for Colon Adenocarcinoma 

Author(s):  
Binbin Cui ◽  
Fuqiang Zhao ◽  
Yanlong Liu ◽  
Xinyue Gu ◽  
Bomiao Zhang ◽  
...  

Abstract Purpose Colon adenocarcinoma (COAD) is the most common primary malignant tumor of the digestive tract. It is still important to find important markers that affect the prognosis of COAD. This research aims to identify some key prognosis-related metabolic genes (PRMG) and establish a clinical prognosis model for COAD patients. Method We used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to obtain gene expression profiles of COAD, and then identified differentially expressed prognostic-related metabolic genes through R language and Perl software, Through univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis to obtain target genes, established metabolic genes prognostic models and risk scores. Through COX regression analysis, independent risk factors affecting the prognosis of COAD were analyzed, and Receiver Operating Characteristic (ROC) curve analysis of independent prognostic factors was performed and a nomogram for predicting overall survival was constructed. Perform the consistency index (C-index) test and decision curve analysis (DCA) on the nomogram, and use Gene Set Enrichment Analysis (GSEA) to identify the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of model genes. Result We selected PRMG based on the expression of metabolic genes, and used LASSO Cox regression to construct 16 metabolic gene (SEPHS1, P4HA1, ENPP2, PTGDS, GPX3, CP, ASPA, POLR3A, PKM, POLR2D , XDH, EPHX2, ADH1B, HMGCL, GPD1L and MAOA) models. The risk score generated from our model can well predict the survival prognosis of COAD. A nomogram based on the clinicopathological characteristics and risk scores of COAD can personally predict the overall survival rate of COAD patients. Conclusion We comprehensively identified metabolic genes related to the prognosis of COAD. The risk score based on the expression of 16 metabolic genes can effectively predict the prognosis of patients with COAD.

Author(s):  
Fu-qiang Zhao ◽  
Yan-long Liu ◽  
Xin-yue Gu ◽  
Bomiao Zhang ◽  
Chengxin Song ◽  
...  

Purpose Colon adenocarcinoma is the most common primary malignant tumor of the digestive tract. It is still important to find important markers that affect the prognosis of COAD. This research aims to identify some key prognosis-related metabolic genes (PRMG) and establish a clinical prognosis model for COAD patients. Method We used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to obtain gene expression profiles of COAD, and then identified differentially expressed prognostic-related metabolic genes through R language and Perl software, Through univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis to obtain target genes, established metabolic genes prognostic models and risk scores. Through COX regression analysis, independent risk factors affecting the prognosis of COAD were analyzed, and Receiver Operating Characteristic (ROC) curve analysis of independent prognostic factors was performed and a nomogram for predicting overall survival was constructed. Perform the consistency index (C-index) test and decision curve analysis (DCA) on the nomogram, and use Gene Set Enrichment Analysis (GSEA) to identify the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of model genes. Result We selected PRMG based on the expression of metabolic genes, and used LASSO Cox regression to construct 16 metabolic gene (SEPHS1, P4HA1, ENPP2, PTGDS, GPX3, CP, ASPA, POLR3A, PKM, POLR2D , XDH, EPHX2, ADH1B, HMGCL, GPD1L and MAOA) models. The risk score generated from our model can well predict the survival prognosis of COAD. A nomogram based on the clinicopathological characteristics and risk scores of COAD can personally predict the overall survival rate of COAD patients. Conclusion We comprehensively identified metabolic genes related to the prognosis of COAD. The risk score based on the expression of 16 metabolic genes can effectively predict the prognosis of patients with COAD.


2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Sihan Chen ◽  
Guodong Cao ◽  
Wei Wu ◽  
Yida Lu ◽  
Xiaobo He ◽  
...  

Abstract Colon adenocarcinoma (COAD) is a malignant gastrointestinal tumor, often occurring in the left colon, which is regulated by glycolysis-related processes. In past studies, multiple genes that influence the prognosis for survival have been discovered through bioinformatics analysis. However, the prediction of disease prognosis using a single gene is not an accurate method. In the present study, a mechanistic model was established to achieve better prediction for the prognosis of COAD. COAD-related data downloaded from The Cancer Genome Atlas (TCGA) were correlated with the glycolysis process using gene set enrichment analysis (GSEA) to determine the glycolysis-related genes that regulate COAD. Using COX regression analysis, glycolysis-related genes associated with the prognosis of COAD were identified, and the genes screened to establish a predictive model. The risk scores of this model were correlated with relevant clinical data to obtain a connection diagram between the model and survival rate, tumor characteristic data, etc. Finally, genes in the model were correlated with cells in the tumor microenvironment, finding that they affected specific immune cells in the model. Seven genes related to glycolysis were identified (PPARGC1A, DLAT, 6PC2, P4HA1, STC2, ANKZF1, and GPC1), which affect the prognosis of patients with COAD and constitute the model for prediction of survival of COAD patients.


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.


2020 ◽  
Author(s):  
Peng Wang ◽  
Kai Huang ◽  
Miaojing Wu ◽  
Qing Hu ◽  
Chuming Tao ◽  
...  

Abstract Background: Glioma is the most common primary intracranial tumor, accounting for the vast majority of intracranial malignant tumors. Aberrant expression of RNA:5-methylcytosine(m5C) methyltransferases has recently been the focus of research relating to the occurrence and progression of tumors. However, the prognostic value of RNA:m5C methyltransferases in glioma remains unclear. This study investigated RNA: m5C methyltransferase expression and defined its clinicopathological signature and prognostic value in gliomas. Methods: We systematically studied the RNA-sequence data of RNA:m5C methyltransferases underlying gliomas in the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets and identified different subtypes using Consensus clustering analysis. Gene Ontology (GO) and Gene Set Enrichment analysis (GSEA) was used to annotate the function of these genes. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm analyses were performed to construct the risk score model. Kaplan-Meier method and Receiver operating characteristic (ROC) curves were used to assess the overall survival of glioma patients. Additionally, Cox proportional regression model analysis was developed to address the connections between the risk scores and clinical factors. Results: Consensus clustering of RNA:m5C methyltransferases identified three clusters of gliomas with different prognostic and clinicopathological features. Meanwhile, Functional annotations demonstrated that RNA:m5C methyltransferases were significantly associated with the malignant progression of gliomas. Thereafter, five RNA:m5C methyltransferase genes were screened to construct a risk score model which can be used to predict not only overall survival but also clinicopathological features in gliomas. ROC curves revealed the significant prognostic ability of this signature. In addition, Multivariate Cox regression analyses indicated that the risk score was an independent prognostic factor for glioma outcome. Conclusion: We demonstrated the role of RNA:m5C methyltransferases in the initiation and progression of glioma. We have expanded on the understanding of the molecular mechanism involved, and provided a unique approach to predictive biomarkers and targeted therapy.


2021 ◽  
Author(s):  
Jianyu Zhao ◽  
Bo Liu ◽  
Xiaoping Li

Abstract Background: Adrenocortical carcinoma (ACC) is a rare endocrine cancer that manifests as abdominal masses and excessive steroid hormone levels. Transcription factors (TFs) deregulation is found to be involved in adrenocortical tumorigenesis and cancer progression. This study aimed to construct a TF-based prognostic signature for prediction of survival of ACC patients.Methods: The gene expression profile for ACC patients were downloaded from TCGA and GEO datasets. The univariate Cox analysis was applied to identify survival-related TFs and the LASSO Cox regression was conducted to construct the TF signature. The multivariate analysis was used to reveal the independent prognostic factors.Results: We identified a 13-TF prognostic signature comprised of CREB3L3, NR0B1, CENPA, FOXM1, E2F2, MYBL2, HOXC11, ZIC2, ZNF282, DNMT1, TCF3, ELK4, and KLF6 using the univariate Cox analysis and LASSO Cox regression. The risk score based on the TF-signature could classify patients into low- and high-risk group. Kaplan-Meier analyses showed that patients in the high-risk group had significantly shorter overall survival compared to the low-risk patients. ROC curves showed that the prognostic signature predicted the overall survival of ACC patients with good sensitivity and specificity. Furthermore, the TF-risk score was an independent prognostic factor.Conclusion: Taken together, we identified a 13-TF prognostic marker to predict overall survival in ACC patients.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Jianyi Li ◽  
Xiaojie Tang ◽  
Yukun Du ◽  
Jun Dong ◽  
Zheng Zhao ◽  
...  

Purpose. Osteosarcoma is the most common primary and highly invasive bone tumor in children and adolescents. The purpose of this study is to construct a multi-gene expression feature related to autophagy, which can be used to predict the prognosis of patients with osteosarcoma. Materials and methods. The clinical and gene expression data of patients with osteosarcoma were obtained from the target database. Enrichment analysis of autophagy-related genes related to overall survival (OS-related ARGs) screened by univariate Cox regression was used to determine OS-related ARGs function and signal pathway. In addition, the selected OS-related ARGs were incorporated into multivariate Cox regression to construct prognostic signature for the overall survival (OS) of osteosarcoma. Use the dataset obtained from the GEO database to verify the signature. Besides, gene set enrichment analysis (GSEA) were applied to further elucidate the molecular mechanisms. Finally, the nomogram is established by combining the risk signature with the clinical characteristics. Results. Our study eventually included 85 patients. Survival analysis showed that patients with low riskScore had better OS. In addition, 16 genes were included in OS-related ARGs. We also generate a prognosis signature based on two OS-related ARGs. The signature can significantly divide patients into low-risk groups and high-risk groups, and has been verified in the data set of GEO. Subsequently, the riskScore, primary tumor site and metastasis status were identified as independent prognostic factors for OS and a nomogram were generated. The C-index of nomogram is 0.789 (95% CI: 0.703~0.875), ROC curve and calibration chart shows that nomogram has a good consistency between prediction and observation of patients. Conclusions. ARGs was related to the prognosis of osteosarcoma and can be used as a biomarker of prognosis in patients with osteosarcoma. Nomogram can be used to predict OS of patients and improve treatment strategies.


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

Abstract Background. We aimed to establish a model to predict the prognosis of patients with thyroid cancer based on differentially expressed hypoxia-related genes.Methods. By comparing the genes in TCGA database and hypoxiaDB database, we obtained differentially expressed genes (DEGs) related to hypoxia in thyroid cancer. Gene function enrichment analysis was performed, and a protein-protein interaction network was constructed using the STRING database. Univariate Cox regression were used to screen hypoxia-related genes with prognostic value. Subsequently, multivariate Cox analysis was used to determine prognostic markers based on thyroid cancer, a prognosis model based on these genes was established. The Kaplan-Meier analysis, Receiver operating characteristic (ROC) analysis and The Harrell’s concordance indexes in the training set and the validation set were used to evaluate the performance of the model. Finally, we conducted univariate analyses of the prognostic value of clinical data (including risk scores) of thyroid cancer patients.Results. 326 hypoxia-related thyroid cancer genes were found. Functional enrichment analysis demonstrated they were mainly involved in regulating biological functions. 23 genes have been proved to be associated with the prognosis of thyroid cancer with univariate Cox regression, among them, 11 marker genes were used to construct a new prognosis model by multivariate Cox analysis. Accordingly, the system of risk scores was constructed, patients with high-risk scores (P <0.005) had shorter overall survival than those with low-risk scores. The ROC curve indicated good performance of the eleven-gene signature at predicting overall survival. The Harrell’s concordance indexes in the internally validated for the 11-gene prognostic signature was 0.881. Moreover, univariate analysis showed that the risk score and age were significantly associated with patient overall survival. The model we created was significantly associated with patient overall survival.Conclusions. The model we established had excellent performance in the prognosis of thyroid cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Kang-Wen Xiao ◽  
Zhi-Bo Liu ◽  
Zi-Hang Zeng ◽  
Fei-Fei Yan ◽  
Ling-Fei Xiao ◽  
...  

Background. Osteosarcoma is one of the most common bone tumors among children. Tumor-associated macrophages have been found to interact with tumor cells, secreting a variety of cytokines about tumor growth, metastasis, and prognosis. This study aimed to identify macrophage-associated genes (MAGs) signatures to predict the prognosis of osteosarcoma. Methods. Totally 384 MAGs were collected from GSEA software C7: immunologic signature gene sets. Differential gene expression (DGE) analysis was performed between normal bone samples and osteosarcoma samples in GSE99671. Kaplan–Meier survival analysis was performed to identify prognostic MAGs in TARGET-OS. Decision curve analysis (DCA), nomogram, receiver operating characteristic (ROC), and survival curve analysis were further used to assess our risk model. All genes from TARGET-OS were used for gene set enrichment analysis (GSEA). Immune infiltration of osteosarcoma sample was calculated using CIBERSORT and ESTIMATE packages. The independent test data set GSE21257 from gene expression omnibus (GEO) was used to validate our risk model. Results. 5 MAGs (MAP3K5, PML, WDR1, BAMBI, and GNPDA2) were screened based on protein-protein interaction (PPI), DGE, and survival analysis. A novel macrophage-associated risk model was constructed to predict a risk score based on multivariate Cox regression analysis. The high-risk group showed a worse prognosis of osteosarcoma ( p  < 0.001) while the low-risk group had higher immune and stromal scores. The risk score was identified as an independent prognostic factor for osteosarcoma. MAGs model for diagnosis of osteosarcoma had a better net clinical benefit based on DCA. The nomogram and ROC curve also effectively predicted the prognosis of osteosarcoma. Besides, the validation result was consistent with the result of TARGET-OS. Conclusions. A novel macrophage-associated risk score to differentiate low- and high-risk groups of osteosarcoma was constructed based on integrative bioinformatics analysis. Macrophages might affect the prognosis of osteosarcoma through macrophage differentiation pathways and bring novel sights for the progression and prognosis of osteosarcoma.


2021 ◽  
Vol 10 ◽  
Author(s):  
Yangyang Wang ◽  
Wenjianlong Zhou ◽  
Shunchang Ma ◽  
Xiudong Guan ◽  
Dainan Zhang ◽  
...  

Glycolysis refers to one of the critical phenotypes of tumor cells, regulating tumor cell phenotypes and generating sufficient energy for glioma cells. A range of noticeable genes [such as isocitrate dehydrogenase (IDH), phosphatase, and tensin homolog (PTEN), or Ras] overall impact cell proliferation, invasion, cell cycle, and metastasis through glycolysis. Moreover, long non-coding RNAs (LncRNAs) are increasingly critical to disease progression. Accordingly, this study aimed to identify whether glycolysis-related LncRNAs have potential prognostic value for glioma patients. First, co-expression network between glycolysis-related protein-coding RNAs and LncRNAs was established according to Pearson correlation (Filter: |r| &gt; 0.5 &amp; P &lt; 0.001). Furthermore, based on univariate Cox regression, the Least Absolute Shrinkage and Selection Operator (LASSO) analysis and multivariate Cox regression, a predictive model were built; vital glycolysis-related LncRNAs were identified; the risk score of every single patient was calculated. Moreover, receiver operating characteristic (ROC) curve analysis, gene set enrichment analysis (GSEA), GO and KEGG enrichment analysis were performed to assess the effect of risk score among glioma patients. 685 cases (including RNA sequences and clinical information) from two different cohorts of the Chinese Glioma Genome Atlas (CGGA) database were acquired. Based on the mentioned methods, the risk score calculation formula was yielded as follows: Risk score = (0.19 × EXPFOXD2-AS1) + (−0.27 × EXPAC062021.1) + (−0.16 × EXPAF131216.5) + (−0.05 × EXPLINC00844) + (0.11 × EXPCRNDE) + (0.35 × EXPLINC00665). The risk score was independently related to prognosis, and every single mentioned LncRNAs was significantly related to the overall survival of patients. Moreover, functional enrichment analysis indicated that the biologic process of the high-risk score was mainly involved in the cell cycle and DNA replication signaling pathway. This study confirmed that glycolysis-related LncRNAs significantly impact poor prognosis and short overall survival and may act as therapeutic targets in the future.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Xu ◽  
Yida Lu ◽  
Youliang Wu ◽  
Mingliang Wang ◽  
Xiaodong Wang ◽  
...  

Abstract Background Gastric cancer (GC) has a high mortality rate and is one of the most fatal malignant tumours. Male sex has been proven as an independent risk factor for GC. This study aimed to identify immune-related genes (IRGs) associated with the prognosis of male GC. Methods RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs between male GC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analyses were applied to screen survival-associated IRGs. Then, GC patients were separated into high- and low-risk groups based on the median risk score. Furthermore, a nomogram was constructed based on the TCGA dataset. The prognostic value of the risk signature model was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell’s concordance index and calibration curves. In addition, the gene expression dataset from the Gene Expression Omnibus (GEO) was also downloaded for external validation. The relative proportions of 22 types of infiltrating immune cells in each male GC sample were evaluated using CIBERSORT. Results A total of 276 differentially expressed IRGs were screened, including 189 up-regulated and 87 down-regulated genes. Subsequently, a seven-IRGs signature (LCN12, CCL21, RNASE2, CGB5, NRG4, AGTR1 and NPR3) was identified to be significantly associated with the overall survival (OS) of male GC patients. Survival analysis indicated that patients in the high-risk group exhibited a poor clinical outcome. The results of multivariate analysis revealed that the risk score was an independent prognostic factor. The established nomogram could be used to evaluate the prognosis of individual male GC patients. Further analysis showed that the prognostic model had excellent predictive performance in both TCGA and validated cohorts. Besides, the results of tumour-infiltrating immune cell analysis indicated that the seven-IRGs signature could reflect the status of the tumour immune microenvironment. Conclusions Our study developed a novel seven-IRGs risk signature for individualized survival prediction of male GC patients.


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