Construction and Validation of a Prognostic Prediction Model for Gastric Cancer Using a Series of Genes Related to Lactate Metabolism

2021 ◽  
Author(s):  
Siyu Wang ◽  
Yuxin Wang ◽  
Xin Wang ◽  
Shuqiang Yuan
Keyword(s):  
Gastric Cancer ◽  
Prediction Model ◽  
Function Analysis ◽  
Differential Expression Analysis ◽  
External Validation ◽  
High Morbidity ◽  
Lactate Metabolism ◽  
Training Cohort ◽  
Cox Regression Analysis ◽  
Prognostic Prediction

Abstract Background: Gastric cancer is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. The commonly used TNM staging and some common biomarkers have a certain value in predicting the prognosis of GC patients, but they gradually failed to meet the clinical demands. Therefore, we aim to construct a prognostic prediction model for GC patients.Methods: A total of 350 cases were included as TCGA-STAD entire cohort, including TCGA-STAD training cohort (n=176) and TCGA-STAD testing cohort (n=174). GSE15459 (n=191), GSE62254 (n=300) and some cases in our center (n=12) were for external validation.Results: Through differential expression analysis and univariate Cox regression analysis in TCGA-STAD training cohort, we screened out 5 genes among 600 genes related to lactate metabolism for the construction of our prognostic prediction model. The internal and external validations showed the same result, that is, patients with higher risk score were associated with poor prognosis (all P<0.05), and our model works well without regard of patients' age, gender, tumor grade, clinical stage or TNM stage, which supports the availability, validity and stability of our model. Gene function analysis, tumor-infiltrating immune cells analysis, tumor microenvironment analysis and clinical treatment exploration were performed to improve the practicability of the model, and hope to provide a new basis for more in-depth study of the molecular mechanism for GC and for clinicians to formulate more reasonable and individualized treatment plans.Conclusions: We screened out and used 5 genes related to lactate metabolism to develop a prognostic prediction model for GC patients based on them. The prediction performance of the model is confirmed by a series of bioinformatics and statistical analysis.

scholarly journals Trends of incidence and prognosis of primary adenocarcinoma of the bladder

2021 ◽  
Vol 13 ◽  
pp. 175628722110180
Author(s):  
Haowen Lu ◽  
Weidong Zhu ◽  
Weipu Mao ◽  
Feng Zu ◽  
Yali Wang ◽  
...  
Keyword(s):  
Prediction Model ◽  
Marital Status ◽  
Cox Regression ◽  
Tnm Staging ◽  
Primary Site ◽  
Primary Adenocarcinoma ◽  
Cancer Specific Survival ◽  
Training Cohort ◽  
Cox Regression Analysis ◽  
Ajcc Stage

Background: Primary adenocarcinoma of the bladder (ACB) is a rare malignant tumor of the bladder with limited understanding of its incidence and prognosis. Methods: Patients diagnosed with ACB between 2004 and 2015 were obtained from the SEER database. The incidence changes of ACB patients between 1975 and 2016 were detected by Joinpoint software. Nomograms were constructed based on the results of multivariate Cox regression analysis to predict overall survival (OS) and cancer-specific survival (CSS) in patients with ACB, and the constructed nomograms were validated. Results: The incidence of ACB was trending down from 1991 to 2016. A total of 1039 patients were included in the study and randomly assigned to the training cohort (727) and validation cohort (312). In the training cohort, multivariate Cox regression showed that age, marital status, primary site, histology type, grade, AJCC stage, T stage, SEER stage, surgery, radiotherapy, and chemotherapy were independent prognostic factors for OS, whereas these were age, marital status, primary site, histology type, grade, AJCC stage, T/N stage, SEER stage, surgery, and radiotherapy for CSS. Based on the above Cox regression results, we constructed prognostic nomograms for OS and CSS in ACB patients. The C-index of the nomogram OS was 0.773 and the C-index of CSS was 0.785, which was significantly better than the C-index of the TNM staging prediction model. The area under the curve (AUC) and net benefit of the prediction model were higher than those of the TNM staging system. In addition, the calibration curves were very close to the ideal curve, suggesting appreciable reliability of the nomograms. Conclusion: The incidence of ACB patients showed a decreasing trend in the past 25 years. We constructed a clinically useful prognostic nomogram for calculating OS and CSS of ACB patients, which can provide a personalized risk assessment for ACB patient survival.

scholarly journals Prediction model of bleeding after endoscopic submucosal dissection for early gastric cancer: BEST-J score

Gut ◽  
2020 ◽  
pp. gutjnl-2019-319926 ◽  
Author(s):  
Waku Hatta ◽  
Yosuke Tsuji ◽  
Toshiyuki Yoshio ◽  
Naomi Kakushima ◽  
Shu Hoteya ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Early Gastric Cancer ◽  
Prediction Model ◽  
Endoscopic Submucosal Dissection ◽  
Clinical Decision Making ◽  
Validation Cohort ◽  
External Validation ◽  
Derivation Cohort ◽  
Submucosal Dissection

ObjectiveBleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is a frequent adverse event after ESD. We aimed to develop and externally validate a clinically useful prediction model (BEST-J score: Bleeding after ESD Trend from Japan) for bleeding after ESD for EGC.DesignThis retrospective study enrolled patients who underwent ESD for EGC. Patients in the derivation cohort (n=8291) were recruited from 25 institutions, and patients in the external validation cohort (n=2029) were recruited from eight institutions in other areas. In the derivation cohort, weighted points were assigned to predictors of bleeding determined in the multivariate logistic regression analysis and a prediction model was established. External validation of the model was conducted to analyse discrimination and calibration.ResultsA prediction model comprised 10 variables (warfarin, direct oral anticoagulant, chronic kidney disease with haemodialysis, P2Y12 receptor antagonist, aspirin, cilostazol, tumour size >30 mm, lower-third in tumour location, presence of multiple tumours and interruption of each kind of antithrombotic agents). The rates of bleeding after ESD at low-risk (0 to 1 points), intermediate-risk (2 points), high-risk (3 to 4 points) and very high-risk (≥5 points) were 2.8%, 6.1%, 11.4% and 29.7%, respectively. In the external validation cohort, the model showed moderately good discrimination, with a c-statistic of 0.70 (95% CI, 0.64 to 0.76), and good calibration (calibration-in-the-large, 0.05; calibration slope, 1.01).ConclusionsIn this nationwide multicentre study, we derived and externally validated a prediction model for bleeding after ESD. This model may be a good clinical decision-making support tool for ESD in patients with EGC.

scholarly journals RNA Binding Protein-Based Model for Prognostic Prediction of Colorectal Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110195
Author(s):  
Ting Li ◽  
Wenjia Hui ◽  
Halina Halike ◽  
Feng Gao
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Rna Binding ◽  
Cox Regression ◽  
Rna Binding Proteins ◽  
Differential Expression Analysis ◽  
High Morbidity ◽  
Sw620 Cell ◽  
Cox Regression Analysis ◽  
Qrt Pcr

Background: Colorectal cancer (CRC) is a kind of gastrointestinal tumor with serious high morbidity and mortality. Several reports have implicated the disorder of RNA-binding proteins (RBPs) in plenty of tumors, associating it to tumorigenesis and disease progression. The study is intended to construct novel prognostic biomarkers associated with CRC patients. Methods: Data of gene expression was acquired from the TCGA database, prognosis-related genes were selected. Besides, we analyzed GO and KEGG pathways. Univariate and multivariate Cox analyses were performed to generate a prognostic-related gene signature, which was evaluated by the Kaplan-Meier (K-M) and the Receiver Operating Characteristic (ROC) curve. The independent prognostic factor was established by survival analysis. GSE38832 dataset was used to validate the signature. Finally, expression of 8 genes was further confirmed by qRT-PCR in SW480 and SW620 cell lines. Results: We obtained 224 differentially expressed RBPS in total, of which 78 were downregulated and 146 were upregulated. Univariate COX analysis was conducted in the TCGA cohort to select 13 RBPs with P < 0.005, stepwise multivariate COX regression analysis was used to construct an 8—RBP signature (TERT, PPARGC1A, BRCA1, CELF4, TDRD7, LUZP4, PNLDC1, ZC3H12C). Based on the model, systematic analysis illustrated that a high risk score was obviously connected to a poor prognosis. The prognostic value of the risk score was validated in GSE38832 dataset, indicating that the risk model was accurate and effective. The prognostic signature-based risk score was identified as an independent prognostic indicator for CRC. The expression results of qRT-PCR were consistent with the results of differential expression analysis. Conclusions: The eight-RBP signature can predict the survival of CRC patients and potentially act as CRC prognostic biomarker.

scholarly journals Establishment of the Radiologic Tumor Invasion Index Based on Radiomics Splenic Features and Clinical Factors to Predict Serous Invasion of Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Bujian Pan ◽  
Weiteng Zhang ◽  
Wenjing Chen ◽  
Jingwei Zheng ◽  
Xinxin Yang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gastric Cancer ◽  
Prediction Model ◽  
Tumor Invasion ◽  
Training Group ◽  
P Value ◽  
Serosal Invasion ◽  
Invasion Risk ◽  
Training Cohort ◽  
Invasion Index

BackgroundCurrently, there are shortcomings in diagnosing gastric cancer with or without serous invasion, making it difficult for patients to receive appropriate treatment. Therefore, we aimed to develop a radiomic nomogram for preoperative identification of serosal invasion.MethodsWe selected 315 patients with gastric cancer, confirmed by pathology, and randomly divided them into two groups: the training group (189 patients) and the verification group (126 patients). We obtained patient splenic imaging data for the training group. A p-value of &lt;0.05 was considered significant for features that were selected for lasso regression. Eight features were chosen to construct a serous invasion prediction model. Patients were divided into high- and low-risk groups according to the radiologic tumor invasion risk score. Subsequently, univariate and multivariate regression analyses were performed with other invasion-related factors to establish a visual combined prediction model.ResultsThe diagnostic accuracy of the radiologic tumor invasion score was consistent in the training and verification groups (p&lt;0.001 and p=0.009, respectively). Univariate and multivariate analyses of invasion risk factors revealed that the radiologic tumor invasion index (p=0.002), preoperative hemoglobin &lt;100 (p=0.042), and the platelet and lymphocyte ratio &lt;92.8 (p=0.031) were independent risk factors for serosal invasion in the training cohort. The prediction model based on the three indexes accurately predicted the serosal invasion risk with an area under the curve of 0.884 in the training cohort and 0.837 in the testing cohort.ConclusionsRadiological tumor invasion index based on splenic imaging combined with other factors accurately predicts serosal invasion of gastric cancer, increases diagnostic precision for the most effective treatment, and is time-efficient.

scholarly journals Construction and Validation of a Universal Applicable Prognostic Signature for Gastric Cancer Based on Seven Immune-Related Gene Correlated With Tumor Associated Macrophages

2021 ◽  
Vol 11 ◽  
Author(s):  
Junyu Huo ◽  
Liqun Wu ◽  
Yunjin Zang
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Risk Score ◽  
Critical Role ◽  
External Validation ◽  
Low Risk ◽  
Prognostic Signature ◽  
Tumor Associated Macrophages ◽  
Cox Regression Analysis ◽  
Significant Difference

BackgroundTumor-associated macrophages (TAMs) play a critical role in the progression of malignant tumors, but the detailed mechanism of TAMs in gastric cancer (GC) is still not fully explored.MethodsWe identified differentially expressed immune-related genes (DEIRGs) between GC samples with high and low macrophage infiltration in The Cancer Genome Atlas datasets. A risk score was constructed based on univariate Cox analysis and Lasso penalized Cox regression analysis in the TCGA cohort (n=341). The optimal cutoff determined by the 5-year time-dependent receiver operating characteristic (ROC) curve was considered to classify patients into groups with high and low risk. We conducted external validation of the prognostic signature in four independent cohorts (GSE84437, n=431; GSE62254, n=300; GSE15459, n=191; and GSE26901, n=109) from the Gene Expression Omnibus (GEO) database.ResultsThe signature consisting of 7 genes (FGF1, GRP, AVPR1A, APOD, PDGFRL, CXCR4, and CSF1R) showed good performance in predicting overall survival (OS) in the 5 independent cohorts. The risk score presented an obviously positive correlation with macrophage abundance (cor=0.7, p&lt;0.001). A significant difference was found between the high- and low-risk groups regarding the overall survival of GC patients. The high-risk group exhibited a higher infiltration level of M2 macrophages estimated by the CIBERSORT algorithm. In the five independent cohorts, the risk score was highly positively correlated with the stromal cell score, suggesting that we can also evaluate the infiltration of stromal cells in the tumor microenvironment according to the risk score.ConclusionOur study developed and validated a general applicable prognostic model for GC from the perspective of TAMs, which may help to improve the precise treatment strategy of GC.

scholarly journals A Novel Lactate Metabolism-Related Gene Signature for Predicting Clinical Outcome and Tumor Microenvironment in Hepatocellular Carcinoma

2022 ◽  
Vol 9 ◽  
Author(s):  
Yue Li ◽  
Huanye Mo ◽  
Shengli Wu ◽  
Xin Liu ◽  
Kangsheng Tu
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Tumor Microenvironment ◽  
External Validation ◽  
Gene Signature ◽  
Metabolic Reprogramming ◽  
Lactate Metabolism ◽  
Related Gene ◽  
High Group ◽  
Cox Regression Analysis

Hepatocellular carcinoma (HCC) is the main subtype of primary liver cancer with high malignancy and poor prognosis. Metabolic reprogramming is a hallmark of cancer and has great importance on the tumor microenvironment (TME). As an abundant metabolite, lactate plays a crucial role in cancer progression and the immunosuppressive TME. Nonetheless, the potential roles of lactate in HCC remain unclear. In this study, we downloaded transcriptomic data of HCC patients with corresponding clinical information from the TCGA and ICGC portals. The TCGA-HCC dataset used as the training cohort, while the ICGC-LIRI-JP dataset was served as an external validation cohort. Cox regression analysis and the LASSO regression model were combined to construct the lactate metabolism-related gene signature (LMRGS). Then, we assessed the clinical significance of LMRGS in HCC. Besides, enriched molecular functions, tumor mutation burden (TMB), infiltrating immune cells, and immune checkpoint were comprehensively analyzed in different LMRGS subgroups. In total, 66 differentially expressed lactate metabolism-related genes (LMRGs) were screened. The functions of LMRGs were mainly enriched in mitochondrial activity and metabolic processes. The LMRGS comprised of six key LMRGs (FKTN, PDSS1, PET117, PUS1, RARS1, and RNASEH1) had significant clinical value for independently predicting the prognosis of HCC patients. The overall survival and median survival of patients in the LMRGS-high group were significantly shorter than in the LMRGS-low group. In addition, there were differences in TMB between the two LMRGS subgroups. The probability of genetic mutations was higher in the LMRGS-high group. Most importantly, the LMRGS reflected the TME characteristics. In the LMRGS-high group, the immune microenvironment presented a suppressed state, accompanied by more inhibitory immune cell infiltration, including follicular helper T cells and regulatory T cells. Additionally, the expression of inhibitory checkpoint molecules was much higher in the LMRGS-high group. Our study suggested that the LMRGS was a robust biomarker to predict the clinical outcomes and evaluate the TME of patients with HCC.

scholarly journals A novel ferroptosis-related genes model for prognosis prediction of lung adenocarcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fei Li ◽  
Dongcen Ge ◽  
Shu-lan Sun
Keyword(s):  
Regression Analysis ◽  
High Risk ◽  
Prediction Model ◽  
Cox Regression ◽  
Risk Group ◽  
Training Set ◽  
Cox Regression Analysis ◽  
Key Genes ◽  
Validation Set ◽  
Prognostic Prediction

Abstract Background Ferroptosis is a newly discovered form of cell death characterized by iron-dependent lipid peroxidation. This study aims to investigate the potential correlation between ferroptosis and the prognosis of lung adenocarcinoma (LUAD). Methods RNA-seq data were collected from the LUAD dataset of The Cancer Genome Atlas (TCGA) database. Based on ferroptosis-related genes, differentially expressed genes (DEGs) between LUAD and paracancerous specimens were identified. The univariate Cox regression analysis was performed to screen key genes associated with the prognosis of LUAD. LUAD patients were divided into the training set and validation set. Then, we screened out key genes and built a prognostic prediction model involving 5 genes using the least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation and the multivariate Cox regression analysis. After dividing LUAD patients based on the median level of risk score as cut-off value, the generated prognostic prediction model was validated in the validation set. Moreover, we analyzed the somatic mutations, and estimated the scores of immune infiltration in the high-risk and low-risk groups. Functional enrichment analysis of DEGs was performed as well. Results High-risk scores indicated the worse prognosis of LUAD. The maximum area under curve (AUC) of the training set and the validation set in this study was 0.7 and 0.69, respectively. Moreover, we integrated the age, gender, and tumor stage to construct the composite nomogram. The charts indicated that the AUC of LUAD cases with the survival time of 1, 3 and 5 years was 0.698, 0.71 and 0.73, respectively. In addition, the mutation frequency of LUAD patients in the high-risk group was significantly higher than that in the low-risk group. Simultaneously, DEGs were mainly enriched in ferroptosis-related pathways by analyzing the functional results. Conclusions This study constructs a novel LUAD prognosis prediction model involving 5 ferroptosis-related genes, which can be used as a promising tool for decision-making of clinical therapeutic strategies of LUAD.

Superior prognosis prediction performance of deep learning for gastric cancer compared to Yonsei prognosis prediction model using Cox regression.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 164-164 ◽  
Author(s):  
Woo Jin Hyung ◽  
Taeil Son ◽  
Minseok Park ◽  
Hansang Lee ◽  
Youn Nam Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Deep Learning ◽  
Prediction Model ◽  
Survival Probability ◽  
Cox Regression ◽  
External Validation ◽  
Prognosis Prediction ◽  
Average Accuracy ◽  
Staging Systems

164 Background: Staging systems for cancer are critical to predict the prognosis of patients. Current staging systems for gastric cancer have limitations to predict individualized and precise prediction of patient’s survival after treatment. We aimed to develop prediction model based on deep learning by estimating the survival probability of patients who underwent gastrectomy. Methods: To predict the survival probability, we used a deep neural network model which consisted of 5 layers: input layer, 3 fully connected layer, and output layer with 8 characteristics (age, sex, histology, depth of tumor, number of metastatic and examined lymph node, presence of distant metastasis, and resection extent) of patients which was previously published Yonsei prediction model using Cox regression. Each layer functioned as the nonlinear weighted sum of lower layer. Five-year overall survival was predicted using the deep learning method and it was compared to Yonsei prediction model. The average area under the curve (AUC) was compared between the models. For internal validation, 5-fold cross validations were carried out. We also performed external validation with a dataset from another hospital (n = 1549). . Results: Deep learning predicted 5-year overall survival of patients with an average accuracy of 83.5% in the test set. The average AUC of deep learning by integrating 8 characteristics was significantly higher than that of Yonsei prediction model (AUC: 0.844 vs. 0.831, P < 0.001) with the same variables. In the external validation the average accuracy of survival prediction was 84.1%. The AUC was also greater in a dataset from other hospital in Korea (AUC: 0.852 vs. 0.847, P = 0.023) Conclusions: Prognosis prediction with deep learning showed superior survival predictive power compared to prediction model using Cox regression. It can provide individualized and precise stratification based on the risk using characteristics of gastric cancer patients.

P0616REAL-TIME CLINICAL DECISION SUPPORT TO PREDICT AND MANAGE IN-HOSPITAL ACUTE KIDNEY INJURY UTILIZING RECURRENT NEURAL NETWORK

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hea Eun Kim ◽  
Hyeonsik Yang ◽  
Sejoong Kim ◽  
Kipyo Kim
Keyword(s):  
Prediction Model ◽  
Validation Cohort ◽  
External Validation ◽  
Vital Signs ◽  
Clinical Decision ◽  
Internal Validation ◽  
Training Cohort ◽  
National University ◽  
Seoul National University ◽  
Dynamic Variables

Abstract Background and Aims Rapidly Increasing electronic health record (EHR) data and recent development of machine learning methods offers the possibilities of improvement in quality of care in clinical practice. Machine learning can incorporate huge amount of features into the model, and enable non-linear algorithms with great performance. Previously published AKI prediction models have simple design without real-time assessment. Major risk factors in in-hospital AKI include use of various nephrotoxins, repeatedly measured laboratory findings, and vital signs, which are dynamic variables rather than static. Given that recurrent neural network (RNN) is a powerful tool to handle the sequential data, using RNN method in the prediction model is a promising approach. Therefore, in the present study, we proposed a RNN-based prediction model with external validation for in-hospital AKI and aimed to provide a framework to link the developed model with clinical decision supports. Method Study populations were all patients aged ≥ 18 years and hospitalized more than a week at Seoul National University Bundang Hospital (SNUBH) from 2013 to 2017 (training cohort) and at Seoul National University Hospital (SNUH) in 2017 (validation cohort). All demographics, laboratory values, vital signs, and clinical conditions were obtained from the EHR of each hospital. A total of 102 variables included in the model. Each variable falls into two categories: static and dynamic variable; static variable was time-invariant values during hospitalization, and dynamic variables were daily-updated values. Baseline creatinine was determined by searching the minimum serum Cr level within 2 weeks before admission. We developed two different models (model 1 and model 2) using RNN algorithms. The outcome for model 1 was the occurrence of AKI within 7 days from the present. In model 2, we constructed the prediction model of the trajectory of Cr values after 24 hours, 48 hours, and 72 hours, using available Cr values from 7 days ago to the present. Internal validation was performed by 5-fold cross validation using the training set (SNUBH), and then external validation was done using test set (SNUH). Results A total of 40,552 patients in training cohort and 4,000 patients in external validation cohort (test cohort) were included in the study. The mean age of participants was 62.2 years in training cohort and 58.7 years in test cohort. Baseline eGFR was 93.8 ± 40.4 ml/min/1.73m2 in training cohort and 88.4 ± 23.2 ml/min/1.73m2 in test cohort. In model 1 for the prediction of AKI occurrence within 7 days, the area under the curve was 0.93 (sensitivity 0.90, specificity 0.96) in internal validation, and 0.83 (sensitivity 0.83, specificity 0.82) in external validation. The model 2 predicted the creatinine trajectory within 3 days accurately; root mean square error was 0.1 in training cohort and 0.3 in test cohort. To support the clinical decision for AKI manage, we estimated the predicted trajectories of future creatinine levels after renal insult removal, such as nephrotoxic drugs, based on the established model 2. Conclusion We developed and validated a real-time AKI prediction model using RNN algorithms. This model showed high performance and can accurately visualize future creatinine trajectories. In addition, the model can provide the information about modifiable factors in patients with high risk of AKI.

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