Construction and validation of a ubiquitination-related prognostic risk score signature in breast cancer
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ABSTRACT:
SUBMITTER: Feng K
PROVIDER: S-EPMC11336713 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
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Project description:Breast cancer is one of the most lethal malignancies among women, and understanding the effects of host immunity on disease progression offers the potential to improve immunotherapies against it. Here, we constructed an immunity-related gene (IRG)-based prognostic signature to stratify breast cancer patients and predict their survival. We identified differentially-expressed genes by analyzing the breast cancer transcriptome data from The Cancer Genome Atlas. Univariate Cox regression revealed 179 survival-correlated IRGs, 12 of which we used to construct an immunity-based prognostic signature that stratified breast cancer patients into high- and low-risk groups. The signature was an independent predictor for survival and was validated in an independent dataset. We also investigated the correlations between our prognostic signature and immune infiltrates and found that signature-derived risk scores correlated negatively with infiltration of B cells, CD4+ T cells, CD8+ T cells, neutrophils and dendritic cells. Our results show that the proposed prognostic signature reflects the tumor immune microenvironment, which makes it a potential indicator for survival that warrants further research to assess its clinical utility.
| S-EPMC7695418 | biostudies-literature
Project description:BackgroundHepatocellular 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.MethodsDifferential 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.ResultsTo 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.ConclusionA 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.
| S-EPMC8529386 | biostudies-literature
Project description:Despite continual efforts to establish pre-operative prognostic model of gastric cancer by using clinical and pathological parameters, a staging system that reliably separates patients with early and advanced gastric cancer into homogeneous groups with respect to prognosis does not exist. With use of microarray and quantitative RT-PCR technologies, we exploited series of experiments in combination with complementary data analyses on tumor specimens from 161 gastric cancer patients. Various statistical analyses were applied to gene expression data to uncover subgroups of gastric cancer, to identify potential biomarkers associated with prognosis, and to construct molecular predictor of risk from identified prognostic biomarkers.Two subgroups of gastric cancer with strong association with prognosis were uncovered. The robustness of prognostic gene expression signature was validated in independent patient cohort with use of support vector machines prediction model. For easy translation of our finding to clinics, we develop scoring system based on expression of six genes that can predict the likelihood of recurrence after curative resection of tumors. In multivariate analysis, our novel risk score was an independent predictor of recurrence (P=0.004) in cohort of 96 patients, and its robustness was validated in two other independent cohorts. We identified novel prognostic subgroups of gastric cancer that are distinctive in gene expression patterns. Six-gene signature and risk score derived from them has been validated for predicting the likelihood of survival at diagnosis. 65 primary gastric adenocarcinoma, 6 GIST and 19 surrounding normal fresh frozen tissues were used for microarray. All the tissues were obtained after curative resection after pathologic confirm at Yonsei cancer center(Seoul, Korea). Microarray experiment and data analysis were done at Dept. of systems biology, MDACC DNA microarray (Illumina human V3)
2011-07-18 | E-GEOD-13861 | biostudies-arrayexpress
Project description:Despite continual efforts to establish pre-operative prognostic model of gastric cancer by using clinical and pathological parameters, a staging system that reliably separates patients with early and advanced gastric cancer into homogeneous groups with respect to prognosis does not exist. With use of microarray and quantitative RT-PCR technologies, we exploited series of experiments in combination with complementary data analyses on tumor specimens from 161 gastric cancer patients. Various statistical analyses were applied to gene expression data to uncover subgroups of gastric cancer, to identify potential biomarkers associated with prognosis, and to construct molecular predictor of risk from identified prognostic biomarkers.Two subgroups of gastric cancer with strong association with prognosis were uncovered. The robustness of prognostic gene expression signature was validated in independent patient cohort with use of support vector machines prediction model. For easy translation of our finding to clinics, we develop scoring system based on expression of six genes that can predict the likelihood of recurrence after curative resection of tumors. In multivariate analysis, our novel risk score was an independent predictor of recurrence (P=0.004) in cohort of 96 patients, and its robustness was validated in two other independent cohorts. We identified novel prognostic subgroups of gastric cancer that are distinctive in gene expression patterns. Six-gene signature and risk score derived from them has been validated for predicting the likelihood of survival at diagnosis.
2011-07-19 | GSE13861 | GEO
Project description:BackgroundAutophagy related genes (ARGs) regulate lysosomal degradation to induce autophagy, and are involved in the occurrence and development of a variety of cancers. The expression of ARGs in tumor tissues has a great prospect in predicting the survival of patients. The aim of this study was to construct a prognostic risk score model for lung adenocarcinoma (LUAD) based on ARGs.Methods5,786 ARGs were obtained from GeneCards database. Gene expression profiles and clinical data of 395 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. All ARGs expression data were extracted, and The ARGs differentially expressed were identified by R software. Survival analysis of differentially expressed ARGs was performed to screen for ARGs with prognostic value, and functional enrichment analysis was performed. The least absolute selection operator (LASSO) regression and Cox regression model were used to construct a prognostic risk scoring model for ARGs. The receiver operating characteristic (ROC) curve was drawn to obtain the optimal cut-off value of risk score. According to the cut-off value, the patients were divided into high-risk group and low-risk group. The area under curve (AUC) and the Kaplan-Meier survival curve was plotted to evaluate the model performance, which was verified in external data sets. Finally, univariate and multivariate Cox regression analysis was applied to evaluate the independent prognostic value of the model, and its clinical relevance was analyzed.ResultsSurvival analysis, Lasso regression and Cox regression analysis were used to construct a LUAD prognostic risk score model with five ARGs (ADAM12, CAMP, DKK1, STRIP2 and TFAP2A). The survival time of patients with low-risk score in this model was significantly better than that of patients with high-risk score (P<0.001). The model showed good prediction performance for LUAD in both the training set (AUCmax=0.78) and two external validation sets (AUCmax=0.88). Risk score was significantly associated with the prognosis of LUAD patients in univariate and multivariate Cox regression analyses, suggested that risk score could be a potential independent prognostic factor for LUAD. Correlation analysis of clinical characteristic showed that high risk score was closely associated with high T stage, high tumor stage and poor prognosis.ConclusionsWe constructed a LUAD risk score model consisting of five ARGs, which can provide a reference for predicting the prognosis of LUAD patients, and may be used in combination with tumor node metastasis (TNM) staging for prognosis prediction of LUAD patients in the future.
| S-EPMC8387651 | biostudies-literature
Project description:Colon cancer is one of the most common cancers, great progress was taken place in the treatment of colon cancer, however, the prognostic assessment system remains lagging. Cell cycle plays a vital role in the whole procedure of cancers. In this study, we firstly identified cell cycle-related genes specific in colon cancer. Functional enrichment analysis proved our analysis reliable. Furthermore, we constructed a robust signature based on the cell cycle-related genes. The AUC of the signature to predict the overall survival was 0.808, 0.807, and 0.831 of AUC at 1, 3, and 5 years, respectively. Internal and external validation proved the signature efficient. The 9 genes involved in the signature also showed a great job in molecular subgrouping which indicated the significant value of the 9 genes for further experimental research. In conclusion, the present research provided a novel robust signature predicting the prognosis of colon cancer.
| S-EPMC7701219 | biostudies-literature
Project description:Breast cancer (BC) is one of the most common tumor types and has poor outcomes. In this study, a ubiquitination-related prognostic signature was constructed, and its association with immunotherapy response in BC was explored. A list of ubiquitination-related genes was obtained from the molecular signatures database, and a ubiquitination-related gene signature was obtained by least absolute shrinkage and selection operator Cox regression. The genes, TCN1, DIRAS3, and IZUMO4, had significant influence on BC outcomes. Patients were categorized into two clusters-a high-risk group with poor survival and a low-risk group with greater chances of controlling BC progression. Univariate and multivariate Cox regression analyses revealed that the risk signature was an independent prognostic factor for BC. Gene set enrichment analysis suggested that the high-risk group was enriched in cell cycle and DNA replication pathways. The risk score was positively linked to the tumor microenvironment and negatively correlated with the immunotherapy response. The IC50 values for rapamycin were higher in the low-risk group, whereas those for axitinib, AZD6244, erlotinib, GDC0941, GSK650394, GSK269962A, lapatinib, and PD0325901 were higher in the high-risk group. Therefore, the ubiquitination-related signature is considered a promising tool for predicting a BC patient's immunotherapy response.
| S-EPMC9845272 | biostudies-literature
Project description:BackgroundLong noncoding RNAs (lncRNAs) are emerging as crucial contributors to the development of breast cancer and are involved in the stemness regulation of breast cancer stem cells (BCSCs). LncRNAs are closely associated with the prognosis of breast cancer patients. It is critical to identify BCSC-related lncRNAs with prognostic value in breast cancer.MethodsA co-expression network of BCSC-related mRNAs-lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were used to identify a stemness risk model with prognostic value. Kaplan-Meier analysis, univariate and multivariate Cox regression analyses and receiver operating characteristic (ROC) curve analysis were performed to validate the risk model. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation were conducted to analyze the risk model.ResultsIn this study, BCSC-related lncRNAs in breast cancer were identified. We evaluated the prognostic value of these BCSC-related lncRNAs and eventually obtained a prognostic risk model consisting of 12 BCSC-related lncRNAs (Z68871.1, LINC00578, AC097639.1, AP003119.3, AP001207.3, LINC00668, AL122010.1, AC245297.3, LINC01871, AP000851.2, AC022509.2 and SEMA3B-AS1). The risk model was further verified as a novel independent prognostic factor for breast cancer patients based on the calculated risk score. Moreover, based on the risk model, the low- risk and high-risk groups displayed different stemness statuses.ConclusionsThese findings suggested that the 12 BCSC-related lncRNA signature might be a promising prognostic factor for breast cancer and can promote the management of BCSC-related therapy in clinical practice.
| S-EPMC7461324 | biostudies-literature
Project description:Hypoxia, an important component of the tumor microenvironment, plays a crucial role in the occurrence and progression of cancer. However, to the best of our knowledge, a systematic analysis of a hypoxia-related prognostic signature for breast cancer is lacking and is urgently required. Therefore, in the present study, RNA-seq data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and served as a discovery cohort. Cox proportional hazards regression analysis was performed to construct a 14-gene prognostic signature (PFKL, P4HA2, GRHPR, SDC3, PPP1R15A, SIAH2, NDRG1, BTG1, TPD52, MAFF, ISG20, LALBA, ERRFI1 and VHL). The hypoxia-related signature successfully predicted survival outcomes of the discovery cohort (P<0.001 for the TCGA dataset). Three independent Gene Expression Omnibus databases (GSE10886, GSE20685 and GSE96058) were used as validation cohorts to verify the value of the predictive signature (P=0.007 for GSE10886, P=0.021 for GSE20685, P<0.001 for GSE96058). In the present study, a robust predictive signature was developed for patients with breast cancer, and the findings revealed that the 14-gene hypoxia-related signature could serve as a potential prognostic biomarker for breast cancer.
| S-EPMC7377061 | biostudies-literature
Project description:ObjectiveBladder cancer (BC) is one of the top ten cancers endangering human health but we still lack accurate tools for BC patients' risk stratification. This study aimed to develop an autophagy-related signature that could predict the prognosis of BC. In order to provide clinical doctors with a visual tool that could precisely predict the survival probability of BC patients, we also attempted to establish a nomogram based on the risk signature.MethodsWe screened out autophagy-related genes (ARGs) combining weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) in BC. Based on the screened ARGs, we performed survival analysis and Cox regression analysis to identify potential prognostic biomarkers. A risk signature based on the prognostic ARGs by multivariate Cox regression analysis was established, which was validated by using seven datasets. To provide clinical doctors with a useful tool for survival possibility prediction, a nomogram assessed by the ARG-based signature and clinicopathological features was constructed, verified using four independent datasets.ResultsThree prognostic biomarkers including BOC (P = 0.008, HR = 1.104), FGF7(P = 0.030, HR = 1.066), and MAP1A (P = 0.001, HR = 1.173) were identified and validated. An autophagy-related risk signature was established and validated. This signature could act as an independent prognostic feature in patients with BC (P = 0.047, HR = 1.419). We then constructed two nomograms with and without ARG-based signature and subsequent analysis indicated that the nomogram with ARG signature showed high accuracy for overall survival probability prediction of patients with BC (C-index = 0.732, AUC = 0.816). These results proved that the ARG signature improved the clinical net benefit of the standard model based on clinicopathological features (age, pathologic stage).ConclusionsThree ARGs were identified as prognosis biomarkers in BC. An ARG-based signature was established for the first time, showing strong potential for prognosis prediction in BC. This signature was proven to improve the clinical net benefit of the standard model. A nomogram was established using this signature, which could lead to more effective prognosis prediction for BC patients.
| S-EPMC8252967 | biostudies-literature