scholarly journals Development and Validation of a Novel Prognosis Prediction Model for Patients With Stomach Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Tong Wang ◽  
Weiwei Wen ◽  
Hongfei Liu ◽  
Jun Zhang ◽  
Xiaofeng Zhang ◽  
...  

Background: Stomach adenocarcinoma (STAD) is a significant global health problem. It is urgent to identify reliable predictors and establish a potential prognostic model.Methods: RNA-sequencing expression data of patients with STAD were downloaded from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database. Gene expression profiling and survival analysis were performed to investigate differentially expressed genes (DEGs) with significant clinical prognosis value. Overall survival (OS) analysis and univariable and multivariable Cox regression analyses were performed to establish the prognostic model. Protein–protein interaction (PPI) network, functional enrichment analysis, and differential expression investigation were also performed to further explore the potential mechanism of the prognostic genes in STAD. Finally, nomogram establishment was undertaken by performing multivariate Cox regression analysis, and calibration plots were generated to validate the nomogram.Results: A total of 229 overlapping DEGs were identified. Following Kaplan–Meier survival analysis and univariate and multivariate Cox regression analysis, 11 genes significantly associated with prognosis were screened and five of these genes, including COL10A1, MFAP2, CTHRC1, P4HA3, and FAP, were used to establish the risk model. The results showed that patients with high-risk scores have a poor prognosis, compared with those with low-risk scores (p = 0.0025 for the training dataset and p = 0.045 for the validation dataset). Subsequently, a nomogram (including TNM stage, age, gender, histologic grade, and risk score) was created. In addition, differential expression and immunohistochemistry stain of the five core genes in STAD and normal tissues were verified.Conclusion: We develop a prognostic-related model based on five core genes, which may serve as an independent risk factor for survival prediction in patients with STAD.

Author(s):  
Yongmei Wang ◽  
Guimin Zhang ◽  
Ruixian Wang

Background: This study aims to explore the prognostic values of CT83 and CT83-related genes in lung adenocarcinoma (LUAD). Methods: We downloaded the mRNA profiles of 513 LUAD patients (RNA sequencing data) and 246 NSCLC patients (Affymetrix Human Genome U133 Plus 2.0 Array) from TCGA and GEO databases. According to the median expression of CT83, the TCGA samples were divided into high and low expression groups, and differential expression analysis between them was performed. Functional enrichment analysis of differential expression genes (DEGs) was conducted. Univariate Cox regression analysis and LASSO Cox regression analysis were performed to screen the optimal prognostic DEGs. Then we established the prognostic model. A Nomogram model was constructed to predict the overall survival (OS) probability of LUAD patients. Results: CT83 expression was significantly correlated to the prognosis of LUAD patients. A total of 59 DEGs were identified, and a predictive model was constructed based on six optimal CT83-related DEGs, including CPS1, RHOV, TNNT1, FAM83A, IGF2BP1, and GRIN2A, could effectively predict the prognosis of LUAD patients. The nomogram could reliably predict the OS of LUAD patients. Moreover, the six important immune checkpoints (CTLA4, PD1, IDO1, TDO2, LAG3, and TIGIT) were closely correlated with the Risk Score, which was also differentially expressed between the LUAD samples with high and low-Risk Scores, suggesting that the poor prognosis of LUAD patients with high-Risk Score might be due to the immunosuppressive microenvironments. Conclusion: A prognostic model based on six optimal CT83 related genes could effectively predict the prognosis of LUAD patients.


2021 ◽  
Author(s):  
Rui Feng ◽  
Jian Li ◽  
Weiling Xuan ◽  
Hanbo Liu ◽  
Dexin Cheng ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer and the main cause of cancer mortality. Its high complexity and dismal prognosis bring dramatic difficulty to treatment. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into seeking novel biomarkers for HCC. Methods Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. GO and KEGG pathway analyses were conducted on these genes. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by ICGC validation set. Results Altogether, 42 autophagy-related differential genes were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model was constituted by 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, FKBP1A. Validation confirmed the accuracy and independence of this model in predicting HCC patient’s prognosis. Conclusion A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.


2021 ◽  
Author(s):  
Jixiang Cao ◽  
Xi Chen ◽  
Guang Lu ◽  
Haowei Wang ◽  
Xinyu Zhang ◽  
...  

Abstract Background: Cholangiocarcinoma (CCA) is the most common malignancy of the biliary tract with a dismal prognosis. Increasing evidence suggests that tumor microenvironment (TME) is closely associated with cancer prognosis. However, the prognostic signature for CCA based on TME has not yet been reported. This study aimed to develop a TME-related prognostic signature for accurately predicting the prognosis of patients with CCA. Methods: Based on the TCGA database, we calculated the stromal and immune scores using the ESTIMATE algorithm to assess TME in stromal and immune cells derived from CCA. TME-related differentially expressed genes were identified, followed by functional enrichment analysis and PPI network analysis. Univariate Cox regression analysis, Lasso Cox regression model and multivariable Cox regression analysis were performed to identify and construct the TME-related prognostic gene signature. Gene Set Enrichment Analyses (GSEA) was performed to further investigate the potential molecular mechanisms. The correlations between the risk scores and tumor infiltration immune cells were analyzed using Tumor Immune Estimation Resource (TIMER) database. Results: A total of 784 TME-related differentially expressed genes (DEGs) were identified, which were mainly enriched in immune-related processes and pathways. Among these TME-related DEGs, A novel two‑gene signature (including GAD1 and KLRB1) was constructed for CCA prognosis prediction. The AUC of the prognostic model for predicting the survival of patients at 1-, 2-, and 3- years was 0.811, 0.772, and 0.844, respectively. Cox regression analysis showed that the two‑gene signature was an independent prognostic factor. Based on the risk scores of the prognostic model, CCA patients were divided into high- and low-risk groups, and patients with high-risk score had shorter survival time than those with low-risk score. Furthermore, we found that the risk scores were negatively correlated with TME-scores and the number of several tumor infiltration immune cells, including B cells and CD4+ T cells. Conclusion: Our study established a novel TME-related gene signature to predict the prognosis of patients with CCA. This might provide a new understanding of the potential relationship between TME and CCA prognosis, and serve as a prognosis stratification tool for guiding personalized treatment of CCA patients.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10628
Author(s):  
Juan Chen ◽  
Rui Zhou

Background Lung adenocarcinoma (LUAD) is the most common histological type of lung cancers, which is the primary cause of cancer‐related mortality worldwide. Growing evidence has suggested that tumor microenvironment (TME) plays a pivotal role in tumorigenesis and progression. Hence, we investigate the correlation of TME related genes with LUAD prognosis. Method The information of LUAD gene expression data was obtained from The Cancer Genome Atlas (TCGA). According to their immune/stromal scores calculated by the ESTIMATE algorithm, differentially expressed genes (DEGs) were identified. Then, we performed univariate Cox regression analysis on DEGs to obtain genes that are apparently bound up with LUAD survival (SurGenes). Functional annotation and protein-protein interaction (PPI) was also conducted on SurGenes. By validating the SurGenes with data sets of lung cancer from the Gene Expression Omnibus (GEO), 106 TME related SurGenes were generated. Further, intersection analysis was executed between the 106 TME related SurGenes and hub genes from PPI network, PTPRC and CD19 were obtained. Gene Set Enrichment Analysis and CIBERSORT analysis were performed on PTPRC and CD19. Based on the TCGA LUAD dataset, we conducted factor analysis and Step-wise multivariate Cox regression analysis for 106 TME related SurGenes to construct the prognostic model for LUAD survival prediction. The LUAD dataset in GEO (GSE68465) was used as the testing dataset to confirm the prognostic model. Multivariate Cox regression analysis was used between risk score from the prognostic model and clinical parameters. Result A total of 106 TME related genes were collected in our research totally, which were markedly correlated with the overall survival (OS) of LUAD patient. Bioinformatics analysis suggest them mainly concentrated on immune response, cell adhesion, and extracellular matrix. More importantly, among 106 TME related SurGenes, PTPRC and CD19 were highly interconnected nodes among PPI network and correlated with immune activity, exhibiting significant prognostic potential. The prognostic model was a weighted linear combination of the 106 genes, by which the low-OS LUAD samples could be separated from the high-OS samples with success. This model was also able to rebustly predict the situation of survival (training set: p-value < 0.0001, area under the curve (AUC) = 0.649; testing set: p-value = 0.0009, AUC = 0.617). By combining with clinical parameters, the prognostic model was optimized. The AUC achieved 0.716 for 3 year and 0.699 for 5 year. Conclusion A series of TME-related prognostic genes were acquired in this research, which could reflect immune disorders within TME, and PTPRC and CD19 show the potential to be an indicator for LUAD prognosis and tumor microenvironment modulation. The prognostic model constructed base on those prognostic genes presented a high predictive ability, and may have clinical implications in the overall survival prediction of LUAD.


2021 ◽  
Vol 11 ◽  
Author(s):  
Guoliang Zheng ◽  
GuoJun Zhang ◽  
Yan Zhao ◽  
Zhichao Zheng

We constructed a prognostic risk model for colon adenocarcinoma (COAD) using microRNAs (miRNAs) as biomarkers. Clinical data of patients with COADs and miRNA-seq data were from TCGA, and the differential expression of miRNAs (carcinoma vs. para-carcinoma tissues) was assessed using R software. COAD data were randomly divided into Training and Testing Sets. A linear prognostic risk model was constructed using Cox regression analysis based on the Training Set. Patients were classified as high-risk or low-risk according to the score of the prognostic model. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate model performance. The gene targets in the prognostic model were identified and their biological functions were analyzed. Analysis of COAD and normal cell lines using qPCR was used to verify the model. There were 134 up-regulated and 140 down-regulated miRNAs. We used the Training Set to develop a prognostic model based on the expression of seven miRNAs. ROC analysis indicated this model had acceptable prediction accuracy (area under the curve=0.784). Kaplan-Meier survival analysis showed that overall survival was worse in the high-risk group. Cox regression analysis showed that the 7-miRNA Risk Score was an independent prognostic factor. The 2,863 predicted target genes were mainly enriched in the MAPK, PI3K-AKT, proteoglycans in cancer, and mTOR signaling pathways. For unknown reasons, expression of these miRNAs in cancerous and normal cells differed somewhat from model predictions. Regardless, the 7-miRNA Risk Score can be used to predict COAD prognosis and may help to guide clinical treatment.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Rui Feng ◽  
Jian Li ◽  
Weiling Xuan ◽  
Hanbo Liu ◽  
Dexin Cheng ◽  
...  

Background. Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer. Treatment is dramatically difficult due to its high complexity and poor prognosis. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into novel biomarkers for HCC. Methods. Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. These genes were subjected to GO and KEGG pathway analyses. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by the ICGC validation set. Results. To sum up, 42 differential genes relevant to autophagy were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model constituted 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, and FKBP1A. Validation confirmed the accuracy and independence of this model in predicting the HCC patient’s prognosis. Conclusion. A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.


2020 ◽  
Author(s):  
Zhiming Zhao ◽  
Mengyang Li ◽  
Xianglong Tan ◽  
Rong Liu

Abstract Background Aberrant DNA methylation is often involved in carcinogenesis. This study is designed to establish an epigenetic signature to predict overall survival (OS) of pancreatic ductal adenocarcinoma (PDAC). Methods DNA methylation and RNA-seq data of PDAC patients were downloaded from the Cancer Genome Atlas database, Genotype-Tissue Expression (GTEx), and International Cancer Genome Consortium (ICGC) database. Methylation-related differentially expressed genes (DEGs) were identified using an R package MethylMix. Epigenetic signature and nomogram were established by the LASSO and multivariate Cox regression analysis, respectively. In addition, a joint survival analysis of the gene expression and methylation was performed to identify potential prognostic factors for patients with PDAC. Results There were a total of 56 methylation-related DEGs by MethylMix criteria. After LASSO Cox regression analysis, we developed an epigenetic signature composed of five genes according to their methylation level. The signature was able to divide patients into high-risk and low-risk groups, and the OS between the high-and low-risk groups was more significantly different in both training and validation cohort. The signature is independent of clinicopathological variables and indicated better predictive power. Moreover, we developed a novel prognostic nomogram that combines risk scores with three clinicopathological factors. The joint survival analysis of gene expression and methylation revealed that 24 genes could be independent prognostic factors for OS in PDAC. Conclusions The qualitative signature and nomogram that predict OS at the individualized level and guide therapy for patients with PDAC.


2020 ◽  
Author(s):  
Songling Han ◽  
Wei Zhu ◽  
Qijie Guan ◽  
Zhuoheng Zhong ◽  
Ruoke Zhao ◽  
...  

Abstract Background Stomach adenocarcinoma (STAD) is the most common histological type of stomach cancer, which causes a considerable number of deaths worldwide. This study specifically aimed to identify potential biomarkers and reveal the underlying molecular mechanisms. Methods Gene expression profiles microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The ‘limma’ R package was used to screen the differentially expressed genes (DEGs) between STAD and matched normal tissues. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for function enrichment analyses of DEGs. The data of STAD cases with both RNA sequencing and clinical information of The Cancer Genome Atlas (TCGA) were obtained from Genomic Data Commons (GDC) data portal. Survival curves were analyzed by the Kaplan-Meier method, univariate Cox regression analysis and multivariate Cox regression were performed using ‘survival’ package. CIBERSORT algorithm used approach to characterize the 22 human immune cell composition. Gene expression profiles microarray data and clinical information were downloaded from GEO database to validate prognostic model. Results Three public datasets including 90 STAD patients and 43 healthy controls were used and 44 genes were differentially expressed in all three datasets. These genes were primarily implicated in biological processes including cell adhesion, wound healing and extracellular matrix organization. Seven out of 44 genes showed significant survival differences based on their expression differences. CTHRC1 and LRFN4 were eventually used to constructed risk score and prognostic model by univariate Cox regression and stepwise multivariate Cox regression in The Cancer Genome Atlas (TCGA)-STAD dataset. The group having high risk scores and the group having low risk scores had significant differences in the infiltration level of multiple immune cells including CD4 memory resting T cells, M2 macrophages, memory B cells, resting dendritic cells, eosinophils, and gamma delta T cells. Multivariate Cox regression analyses indicated that the risk score was an independent predictor after adjusting for age, sex, and tumor stage. At last, the model was verified and evaluated by another independent dataset and showed a good classification effect. Conclusions The present study constructed the prognostic model by expression of CTHRC1 and LRFN4 for the first time via comprehensive bioinformatics analysis, which may provide clinical guidance and potential therapeutic targets for STAD.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Chen ◽  
Yuxiang Dong ◽  
Yitong Pan ◽  
Yuhan Zhang ◽  
Ping Liu ◽  
...  

Abstract Background Breast cancer is one of the main malignant tumors that threaten the lives of women, which has received more and more clinical attention worldwide. There are increasing evidences showing that the immune micro-environment of breast cancer (BC) seriously affects the clinical outcome. This study aims to explore the role of tumor immune genes in the prognosis of BC patients and construct an immune-related genes prognostic index. Methods The list of 2498 immune genes was obtained from ImmPort database. In addition, gene expression data and clinical characteristics data of BC patients were also obtained from the TCGA database. The prognostic correlation of the differential genes was analyzed through Survival package. Cox regression analysis was performed to analyze the prognostic effect of immune genes. According to the regression coefficients of prognostic immune genes in regression analysis, an immune risk scores model was established. Gene set enrichment analysis (GSEA) was performed to probe the biological correlation of immune gene scores. P < 0.05 was considered to be statistically significant. Results In total, 556 immune genes were differentially expressed between normal tissues and BC tissues (p < 0. 05). According to the univariate cox regression analysis, a total of 66 immune genes were statistically significant for survival risk, of which 30 were associated with overall survival (P < 0.05). Finally, a 15 immune genes risk scores model was established. All patients were divided into high- and low-groups. KM survival analysis revealed that high immune risk scores represented worse survival (p < 0.001). ROC curve indicated that the immune genes risk scores model had a good reliability in predicting prognosis (5-year OS, AUC = 0.752). The established risk model showed splendid AUC value in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Moreover, the immune risk signature was proved to be an independent prognostic factor for BC patients. Finally, it was found that 15 immune genes and risk scores had significant clinical correlations, and were involved in a variety of carcinogenic pathways. Conclusion In conclusion, our study provides a new perspective for the expression of immune genes in BC. The constructed model has potential value for the prognostic prediction of BC patients and may provide some references for the clinical precision immunotherapy of patients.


2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Bei Li ◽  
Long Fang ◽  
Baolong Wang ◽  
Zengkun Yang ◽  
Tingbao Zhao

Osteosarcoma often occurs in children and adolescents and causes poor prognosis. The role of RNA-binding proteins (RBPs) in malignant tumors has been elucidated in recent years. Our study aims to identify key RBPs in osteosarcoma that could be prognostic factors and treatment targets. GSE33382 dataset was downloaded from Gene Expression Omnibus (GEO) database. RBPs extraction and differential expression analysis was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to explore the biological function of differential expression RBPs. Moreover, we constructed Protein-protein interaction (PPI) network and obtained key modules. Key RBPs were identified by univariate Cox regression analysis and multiple stepwise Cox regression analysis combined with the clinical information from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Risk score model was generated and validated by GSE16091 dataset. A total of 38 differential expression RBPs was identified. Go and KEGG results indicated these RBPs were significantly involved in ribosome biogenesis and mRNA surveillance pathway. COX regression analysis showed DDX24, DDX21, WARS and IGF2BP2 could be prognostic factors in osteosarcoma. Spearman’s correlation analysis suggested that WARS might be important in osteosarcoma immune infiltration. In conclusion, DDX24, DDX21, WARS and IGF2BP2 might play key role in osteosarcoma, which could be therapuetic targets for osteosarcoma treatment.


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