Development and validation of a risk prediction model and nomogram for colon adenocarcinoma based on methylation-driven genes.
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ABSTRACT:
SUBMITTER: Zhu L
PROVIDER: S-EPMC8266312 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: DNA methylation affects the development, progression, and prognosis of various cancers. This study aimed to identify DNA methylated-differentially expressed genes (DEGs) and develop a methylation-driven gene model to evaluate the prognosis of ovarian cancer (OC). Methods: DNA methylation and mRNA expression profiles of OC patients were downloaded from The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases. We used the R package MethylMix to identify DNA methylation-regulated DEGs and built a prognostic signature using LASSO Cox regression. A quantitative nomogram was then drawn based on the risk score and clinicopathological features. Results: We identified 56 methylation-related DEGs and constructed a prognostic risk signature with four genes according to the LASSO Cox regression algorithm. A higher risk score not only predicted poor prognosis, but also was an independent poor prognostic indicator, which was validated by receiver operating characteristic (ROC) curves and the validation cohort. A nomogram consisting of the risk score, age, FIGO stage, and tumor status was generated to predict 3- and 5-year overall survival (OS) in the training cohort. The joint survival analysis of DNA methylation and mRNA expression demonstrated that the two genes may serve as independent prognostic biomarkers for OS in OC. Conclusion: The established qualitative risk score model was found to be robust for evaluating individualized prognosis of OC and in guiding therapy.
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Project description:Background/Aims: The incidence of gastric cancer (GC) ranks fifth among common tumors and GC is the third leading cause of cancer-related death worldwide. The aim of this study was to develop and validate a nomogram for predicting the overall survival (OS) of patients with GC. Methods: DNA methylation (DNAm)-driven genes were identified by integrating DNAm and gene expression profiling analyses from The Cancer Genome Atlas (TCGA) GC cohort. Then, a risk score model was built based on Kaplan-Meier (K-M), least absolute shrinkage and selector operation (LASSO), and multivariate Cox regression analyses. After analyzing the clinical parameters, a nomogram was constructed and assessed. Another cohort (GSE62254) was used for external validation. Results: Thirteen differentially expressed DNAm-driven genes were narrowed down to a six-gene signature (PODN, NPY, MICU3, TUBB6 and RHOJ were hypermethylated, and MYO1A was hypomethylated), which was associated with OS (P < 0.05) after survival and LASSO regression analyses. These differentially expressed genes (DEGs) with altered DNAm statuses were included in the prognostic risk score model. The univariate Cox regression analysis indicated that risk score, age, and number of positive lymph nodes were significantly associated with survival time in GC patients. The multivariate Cox regression analysis also indicated that these variables were significant prognostic factors for GC. A nomogram including these variables was constructed, and its performance in predicting the 1-, 3- and 5-year survival outcomes of GC patients was estimated through time-dependent receiver operating characteristic (ROC) curves. In addition, the clinical benefit of this model was revealed by decision curve analysis (DCA). Pathway enrichment analysis suggested that these DNAm-driven genes might impact tumor progression by affecting signaling pathways such as the "ECM RECEPTOR INTERACTION" and "DNA REPLICATION" pathways. Conclusions: The altered status of the DNAm-driven gene signature (PODN, MYO1A, NPY, MICU3, TUBB6 and RHOJ) was significantly associated with the OS of GC patients. A nomogram incorporating risk score, age and number of positive lymph nodes can be conveniently used to facilitate the individualized prediction of OS in patients with GC.
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Project description:BACKGROUND:Accurate diagnosis of early lung cancer from small pulmonary nodules (SPN) is challenging in clinical setting. We aimed to develop a radiomic nomogram to differentiate lung adenocarcinoma from benign SPN. METHODS:This retrospective study included a total of 210 pathologically confirmed SPN (? 10?mm) from 197 patients, which were randomly divided into a training dataset (n?=?147; malignant nodules, n?=?94) and a validation dataset (n?=?63; malignant nodules, n?=?39). Radiomic features were extracted from the cancerous volumes of interest on contrast-enhanced CT images. The least absolute shrinkage and selection operator (LASSO) regression was used for data dimension reduction, feature selection, and radiomic signature building. Using multivariable logistic regression analysis, a radiomic nomogram was developed incorporating the radiomic signature and the conventional CT signs observed by radiologists. Discrimination and calibration of the radiomic nomogram were evaluated. RESULTS:The radiomic signature consisting of five radiomic features achieved an AUC of 0.853 (95% confidence interval [CI]: 0.735-0.970), accuracy of 81.0%, sensitivity of 82.9%, and specificity of 77.3%. The two conventional CT signs achieved an AUC of 0.833 (95% CI: 0.707-0.958), accuracy of 65.1%, sensitivity of 53.7%, and specificity of 86.4%. The radiomic nomogram incorporating the radiomic signature and conventional CT signs showed an improved AUC of 0.857 (95% CI: 0.723-0.991), accuracy of 84.1%, sensitivity of 85.4%, and specificity of 81.8%. The radiomic nomogram had good calibration power. CONCLUSION:The radiomic nomogram might has the potential to be used as a non-invasive tool for individual prediction of SPN preoperatively. It might facilitate decision-making and improve the management of SPN in the clinical setting.
| S-EPMC7278188 | biostudies-literature
Project description:PurposeThe exploration and interpretation of DNA methylation-driven genes might contribute to molecular classification, prognostic prediction and therapeutic choice. In this study, we built a prognostic risk model via integrating analysis of the transcriptome and methylation profile for patients with gastric cancer (GC).MethodsThe mRNA expression profiles, DNA methylation profiles and corresponding clinicopathological information of 415 GC patients were downloaded from The Cancer Genome Atlas (TCGA). Differential expression and correlation analysis were performed to identify DNA methylation-driven genes. The candidate genes were selected by univariate Cox regression analyses followed by the least absolute shrinkage and selection operator (LASSO) regression. A prognostic risk nomogram model was then built together with clinicopathological parameters.Results5 DNA methylation-driven genes (CXCL3, F5, GNAI1, GAMT and GHR) were identified by integrated analyses and selected to construct the prognostic risk model with clinicopathological parameters. High expression and low DNA hypermethylation of F5, GNAI1, GAMT and GHR, as well as low expression and high DNA hypomethylation of CXCL3 were significantly associated with poor prognosis rates, respectively. The high-risk group showed a significantly shorter prognosis than the low-risk group in the TCGA dataset (HR = 0.212, 95% CI = 0.139-0.322, P = 2e-15). The final nomogram model showed high predictive efficiency and consistency in the training and validation group.ConclusionWe construct and validate a prognostic nomogram model for GC based on five DNA methylation-driven genes with high performance and stability. This nomogram model might be a powerful tool for prognosis evaluation in the clinic and also provided novel insights into the epigenetics in GC.
| S-EPMC7732649 | biostudies-literature
Project description:BackgroundDNA methylation is an important part of epigenetic modification, and its abnormality is closely related to esophageal adenocarcinoma (EAC). This study was aimed at using bioinformatics analysis to identify methylation-driven genes (MDGs) in EAC patients and establish a risk model as a biological indicator of EAC prognosis.MethodDownloaded EAC DNA methylation, transcriptome, and related clinical data from TCGA database. MethylMix was used to identify MDGs. R package clusterProfiler and the ConsensusPathDB online database were used to analyze the rich functions and pathways of these MDGs. The prognostic risk model was established by univariate Cox regression, Lasso regression, and multivariate Cox regression analysis. Finally each MDG in the model were carried out through the survival R package.ResultsA total of 273 MDGs were identified, which were enriched in transcriptional regulation and embryonic organ morphogenesis. Cox regression analysis established a risk model consisting of GPBAR1, OLFM4, FOXI2, and CASP10. In addition, further survival analysis revealed that OLFM4 and its two related sites were significantly related to the EAC patients' survival.ConclusionIn summary, this study used bioinformatics methods to identify EAC MDGs and established a reliable risk prognosis model. It provided potential biomarkers for the early treatment and prognosis evaluation of EAC.
| S-EPMC8213479 | biostudies-literature
Project description:Increasing evidence suggested DNA methylation may serve as potential prognostic biomarkers; however, few related DNA methylation signatures have been established for prediction of lung cancer prognosis. We aimed at developing DNA methylation signature to improve prognosis prediction of stage I lung adenocarcinoma (LUAD). A total of 268 stage I LUAD patients from the Cancer Genome Atlas (TCGA) database were included. These patients were separated into training and internal validation datasets. GSE39279 was used as an external validation set. A 13-DNA methylation signature was identified to be crucially relevant to the relapse-free survival (RFS) of patients with stage I LUAD by the univariate Cox proportional hazard analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis and multivariate Cox proportional hazard analysis in the training dataset. The Kaplan-Meier analysis indicated that the 13-DNA methylation signature could significantly distinguish the high- and low-risk patients in entire TCGA dataset, internal validation and external validation datasets. The receiver operating characteristic (ROC) analysis further verified that the 13-DNA methylation signature had a better value to predict the RFS of stage I LUAD patients in internal validation, external validation and entire TCGA datasets. In addition, a nomogram combining methylomic risk scores with other clinicopathological factors was performed and the result suggested the good predictive value of the nomogram. In conclusion, we successfully built a DNA methylation-associated nomogram, enabling prediction of the RFS of patients with stage I LUAD.
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Project description:BackgroundClinical staging is essential for clinical decisions but remains imprecise. We purposed to construct a novel survival prediction model for improving clinical staging system (cTNM) for patients with esophageal adenocarcioma (EAC).MethodsA total of 4180 patients diagnosed with EAC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and included as the training cohort. Significant prognostic variables were identified for nomogram model development using multivariable Cox regression. The model was validated internally by bootstrap resampling, and then subjected to external validation with a separate cohort of 886 patients from 2 institutions in China. The prognostic performance was measured by concordance index (C-index), Akaike information criterion (AIC) and calibration plots. Different risk groups were stratified by the nomogram scores.ResultsA total of six variables were determined related with survival and entered into the nomogram construction. The calibration curves showed satisfied agreement between nomogram-predicted survival and actual observed survival for 1-, 3-, and 5-year overall survival. By calculating the AIC and C-index values, our nomogram presented superior discriminative and risk-stratifying ability than current TNM staging system. Significant distinctions in survival curves were observed between different risk subgroups stratified by nomogram scores.ConclusionThe established and validated nomogram presented better risk-stratifying ability than current clinical staging system, and could provide a convenient and reliable tool for individual survival prediction and treatment strategy making.
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Project description:PurposeThis study aimed to develop and validate a nomogram with preoperative nutritional indicators and tumor markers for predicting prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).MethodsWe performed a bicentric, retrospective study including 155 eligible patients with PDAC. Patients were divided into a training group (n = 95), an internal validation group (n = 34), an external validation group (n = 26), and an entire validation group (n = 60). Cox regression analysis was conducted in the training group to identify independent prognostic factors to construct a nomogram for overall survival (OS) prediction. The performance of the nomogram was assessed in validation groups and through comparison with controlling nutritional status (CONUT) and prognostic nutrition index (PNI).ResultsThe least absolute shrinkage and selection operator (LASSO) regression, univariate and multivariate Cox regression analysis revealed that serum albumin and lymphocyte count were independent protective factors while CA19-9 and diabetes were independent risk factors. The concordance index (C-index) of the nomogram in the training, internal validation, external validation and entire validation groups were 0.777, 0.769, 0.759 and 0.774 respectively. The areas under curve (AUC) of the nomogram in each group were 0.861, 0.845, 0.773, and 0.814. C-index and AUC of the nomogram were better than those of CONUT and PNI in the training and validation groups. The net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis showed improvement of accuracy of the nomogram in predicting OS and better net benefit in guiding clinical decisions in comparison with CONUT and PNI.ConclusionsThe nomogram incorporating four preoperative nutritional and tumor markers including serum albumin concentration, lymphocyte count, CA19-9 and diabetes mellitus could predict the prognosis more accurately than CONUT and PNI and may serve as a clinical decision support tool to determine what treatment options to choose.
| S-EPMC8200845 | biostudies-literature
Project description: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.
| S-EPMC8727349 | biostudies-literature
Project description:BackgroundDermatomyositis accompanied with malignancy is a common poor prognostic factor of dermatomyositis. Thus, the early prediction of the risk of malignancy in patients with dermatomyositis can significantly improve the prognosis of patients. However, the identification of antibodies related to malignancy in dermatomyositis patients has not been widely implemented in clinical practice. Herein, we established a predictive nomogram model for the diagnosis of dermatomyositis associated with malignancy.MethodsWe retrospectively analyzed 240 cases of dermatomyositis patients admitted to Sun Yat-sen Memorial Hospital, Sun Yat-sen University from January 2002 to December 2019. According to the year of admission, the first 70% of the patients were used to establish a training cohort, and the remaining 30% were assigned to the validation cohort. Univariate analysis was performed on all variables, and statistically relevant variables were further included in a multivariate logistic regression analysis to screen for independent predictors. Finally, a nomogram was constructed based on these independent predictors. Bootstrap repeated sampling calculation C-index was used to evaluate the model's calibration, and area under the curve (AUC) was used to evaluate the model discrimination ability.ResultsMultivariate logistic analysis showed that patients older than 50-year-old, dysphagia, refractory itching, and elevated creatine kinase were independent risk factors for dermatomyositis associated with malignancy, while interstitial lung disease was a protective factor. Based on this, we constructed a nomogram using the above-mentioned five factors. The C-index was 0.780 (95% CI [0.690-0.870]) in the training cohort and 0.756 (95% CI [0.618-0.893]) in the validation cohort, while the AUC value was 0.756 (95% CI [0.600-0.833]). Taken together, our nomogram showed good calibration and was effective in predicting which dermatomyositis patients were at a higher risk of developing malignant tumors.
| S-EPMC8667746 | biostudies-literature