Dataset Information

Construction and Validation of a Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Gastric Cancer.

ABSTRACT:

Background

Increasing evidence indicated that the tumor microenvironment (TME) plays a critical role in tumor progression. This study aimed to identify and evaluate mRNA signature involved in lymph node metastasis (LNM) in TME for gastric cancer (GC).

Methods

Gene expression and clinical data were downloaded from The Cancer Genome Atlas (TCGA). The ESTIMATE algorithm was used to evaluate the TME of GC. The heatmap and Venn plots were applied for visualizing and screening out intersect differentially expressed genes (DEGs) involved in LNM in TME. Functional enrichment analysis, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network were also conducted. Furthermore, binary logistic regression analysis were employed to develop a 4-mRNAs signature for the LNM prediction. ROC curves were applied to validate the LNM predictive ability of the riskscore. Nomogram was constructed and calibration curve was plotted to verify the predictive power of nomogram.

Results

A total of 88 LNM related DEGs were identified. Functional enrichment analysis and GSEA implied that those genes were associated with some biological processes, such as ion transportation, lipid metabolism and thiolester hydrolase activity. After univariate and multivariate logistic regression analysis, 4 mRNAs (RASSF2, MS4A2, ANKRD33B and ADH1B) were eventually screened out to develop a predictive model. ROC curves manifested the good performance of the 4-mRNAs signature. The proportion of patients with LNM in high-risk group was significantly higher than that in low-risk group. The C-index of nomogram from training and test cohorts were 0.865 and 0.765, and the nomogram was well calibrated.

Conclusions

In general, we identified a 4-mRNAs signature that effectively predicted LNM in GC patients. Moreover, the 4-mRNAs signature and nomogram provide a guidance for the preoperative evaluation and postoperative treatment of GC patients.

SUBMITTER: Li S

PROVIDER: S-EPMC8226383 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundPreoperative evaluation of lymph node (LN) state is of pivotal significance for informing therapeutic decisions in gastric cancer (GC) patients. However, there are no non-invasive methods that can be used to preoperatively identify such status. We aimed at developing a genomic biosignature based model to predict the possibility of LN metastasis in GC patients.MethodsWe used the RNA profile retrieving strategy and performed RNA expression profiling in a large GC cohort (GSE62254, n = 300) from Gene Expression Ominus (GEO). In the exploratory stage, 300 GC patients from GSE62254 were involved and the differentially expressed RNAs (DERs) for LN-status were determined using the R software. GC samples in GSE62254 were randomly allocated into a learning set (n = 210) and a verification set (n = 90). By using the Least absolute shrinkage and selection operator (LASSO) regression approach, a set of 23-RNA signatures were established and the signature based nomogram was subsequently built for distinguishing LN condition. The diagnostic efficiency, as well as the clinical performance of this model were assessed using the decision curve analysis (DCA). Metascape was used for bioinformatic analysis of the DERs.ResultsBased on the genomic signature, we established a nomogram that robustly distinguished LN status in the learning (AUC = 0.916, 95% CI 0.833-0.999) and verification sets (AUC = 0.775, 95% CI 0.647-0.903). DCA demonstrated the clinical value of this nomogram. Functional enrichment analysis of the DERs was performed using bioinformatics methods which revealed that these DERs were involved in several lymphangiogenesis-correlated cascades.ConclusionsIn this study, we present a genomic signature based nomogram that integrates the 23-RNA biosignature based scores and Lauren classification. This model can be utilized to estimate the probability of LN metastasis with good performance in GC. The functional analysis of the DERs reveals the prospective biogenesis of LN metastasis in GC.

Project description:PURPOSE:To build and validate a radiomics-based nomogram for the prediction of pre-operation lymph node (LN) metastasis in esophageal cancer. PATIENTS AND METHODS:A total of 197 esophageal cancer patients were enrolled in this study, and their LN metastases have been pathologically confirmed. The data were collected from January 2016 to May 2016; patients in the first three months were set in the training cohort, and patients in April 2016 were set in the validation cohort. About 788 radiomics features were extracted from computed tomography (CT) images of the patients. The elastic-net approach was exploited for dimension reduction and selection of the feature space. The multivariable logistic regression analysis was adopted to build the radiomics signature and another predictive nomogram model. The predictive nomogram model was composed of three factors with the radiomics signature, where CT reported the LN number and position risk level. The performance and usefulness of the built model were assessed by the calibration and decision curve analysis. RESULTS:Thirteen radiomics features were selected to build the radiomics signature. The radiomics signature was significantly associated with the LN metastasis (P<0.001). The area under the curve (AUC) of the radiomics signature performance in the training cohort was 0.806 (95% CI: 0.732-0.881), and in the validation cohort it was 0.771 (95% CI: 0.632-0.910). The model showed good discrimination, with a Harrell's Concordance Index of 0.768 (0.672 to 0.864, 95% CI) in the training cohort and 0.754 (0.603 to 0.895, 95% CI) in the validation cohort. Decision curve analysis showed our model will receive benefit when the threshold probability was larger than 0.15. CONCLUSION:The present study proposed a radiomics-based nomogram involving the radiomics signature, so the CT reported the status of the suspected LN and the dummy variable of the tumor position. It can be potentially applied in the individual preoperative prediction of the LN metastasis status in esophageal cancer patients.

Project description:BackgroundGrowing evidence suggests that tumor metastasis necessitates multi-step microenvironmental regulation. Lymph node metastasis (LNM) influences both pre- and post-operative bladder cancer (BLCA) treatment strategies. Given that current LNM diagnosis methods are still insufficient, we intend to investigate the microenvironmental changes in BLCA with and without LNM and develop a prediction model to confirm LNM status.Method"Estimation of Stromal and Immune cells in Malignant Tumors using Expression data" (ESTIMATE) algorithm was used to characterize the tumor microenvironment pattern of TCGA-BLCA cohort, and dimension reduction, feature selection, and StrLNM signature construction were accomplished using least absolute shrinkage and selection operator (LASSO) regression. StrLNM signature was combined with the genomic mutation to establish an LNM nomogram by using multivariable logistic regression. The performance of the nomogram was evaluated in terms of calibration, discrimination, and clinical utility. The testing set from the TCGA-BLCA cohort was used for internal validation. Moreover, three independent cohorts were used for external validation, and BLCA patients from our cohort were also used for further validation.ResultsThe StrLNM signature, consisting of 22 selected features, could accurately predict LNM status in the TCGA-BLCA cohort and several independent cohorts. The nomogram performed well in discriminating LNM status, with the area under curve (AUC) of 75.1% and 65.4% in training and testing datasets from the TCGA-BLCA cohort. Furthermore, the StrLNM nomogram demonstrated good calibration with p >0.05 in the Hosmer-Lemeshow goodness of fit test. Decision curve analysis (DCA) revealed that the StrLNM nomogram had a high potential for clinical utility. Additionally, 14 of 22 stably expressed genes were identified by survival analysis and confirmed by qPCR in BLCA patient samples in our cohort.ConclusionIn summary, we developed a nomogram that included an StrLNM signature and facilitated the preoperative prediction of LNM status in BLCA patients.

Project description:BACKGROUND:Accurate lymph node metastasis (LNM) prediction in colorectal cancer (CRC) patients is of great significance for treatment decision making and prognostic evaluation. We aimed to develop and validate a clinical-radiomics nomogram for the individual preoperative prediction of LNM in CRC patients. METHODS:We enrolled 766 patients (458 in the training set and 308 in the validation set) with clinicopathologically confirmed CRC. We included nine significant clinical risk factors (age, sex, preoperative carbohydrate antigen 19-9 (CA19-9) level, preoperative carcinoembryonic antigen (CEA) level, tumor size, tumor location, histotype, differentiation and M stage) to build the clinical model. We used analysis of variance (ANOVA), relief and recursive feature elimination (RFE) for feature selection (including clinical risk factors and the imaging features of primary lesions and peripheral lymph nodes), established classification models with logistic regression analysis and selected the respective candidate models by fivefold cross-validation. Then, we combined the clinical risk factors, primary lesion radiomics features and peripheral lymph node radiomics features of the candidate models to establish combined predictive models. Model performance was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Finally, decision curve analysis (DCA) and a nomogram were used to evaluate the clinical usefulness of the model. RESULTS:The clinical-primary lesion radiomics-peripheral lymph node radiomics model, with the highest AUC value (0.7606), was regarded as the candidate model and had good discrimination and calibration in both the training and validation sets. DCA demonstrated that the clinical-radiomics nomogram was useful for preoperative prediction in the clinical environment. CONCLUSION:The present study proposed a clinical-radiomics nomogram with a combination of clinical risk factors and radiomics features that can potentially be applied in the individualized preoperative prediction of LNM in CRC patients.