scholarly journals Nomogram for predicting postoperative cancer-specific early death in patients with epithelial ovarian cancer based on the SEER database: a large cohort study

Author(s):  
Tingting Zhang ◽  
Liancheng Zhu

Abstract Purpose Ovarian cancer is a common gynecological malignant tumor. Poor prognosis is strongly associated with early death, but there is no effective tool to predict this. This study aimed to construct a nomogram for predicting cancer-specific early death in patients with ovarian cancer. Methods We used data from the Surveillance, Epidemiology, and End Results database of patients with ovarian cancer registered from 1988 to 2016. Important independent prognostic factors were determined by univariate and multivariate logistic regression and LASSO Cox regression. Several risk factors were considered in constructing the nomogram. Nomogram discrimination and calibration were evaluated using C-index, internal validation, and receiver operating characteristic (ROC) curves. Results A total of 4769 patients were included. Patients were assigned to the training set (n = 3340; 70%) and validation set (n = 1429; 30%). Based on the training set, eight variables were shown to be significant factors for early death and were incorporated in the nomogram: American Joint Committee on Cancer (AJCC) stage, residual lesion size, chemotherapy, serum CA125 level, tumor size, number of lymph nodes examined, surgery of primary site, and age. The concordance indices and ROC curves showed that the nomogram had better predictive ability than the AJCC staging system and good clinical practicability. Internal validation based on validation set showed good consistency between predicted and observed values for early death. Conclusion Compared with predictions made based on AJCC stage or residual lesion size, the nomogram could provide more robust predictions for early death in patients with ovarian cancer.

2021 ◽  
Author(s):  
Tingting Zhang ◽  
Liancheng Zhu

Abstract Background: Ovarian cancer is a common gynecological malignant tumor. Poor prognosis is strongly associated with early death, but there is no effective tool to predict this. This study aimed to construct a nomogram for predicting cancer-specific early death in ovarian cancer patients.Methods: Our study used data from the Surveillance, Epidemiology, and End Results (SEER) database of ovarian cancer patients registered from 1988 to 2016. Important independent prognostic factors were determined by univariate and multivariate logistic regression and LASSO Cox regression. Several risk factors were considered in constructing the nomogram. Nomogram discrimination and calibration were evaluated using C-index, internal validation, and receiver operating characteristic (ROC) curves.Results: A total of 4769 patients were included. Patients were assigned to the training set (n = 3340; 70%) and validation set (n = 1429; 30%). Based on the training set, eight variables were shown to be significant factors for early death and were incorporated in the nomogram: AJCC (American Joint Committee on Cancer) stage, residual lesion size, chemotherapy, serum CA125 level, tumor size, number of lymph nodes examined, surgery of primary site, and age. The C-indices and ROC curves showed that the nomogram had better predictive ability than the AJCC staging system and good clinical practicability. Internal validation based on validation set showed good consistency between predicted and observed values for early death. Conclusions: Compared with predictions made using AJCC stage or residual lesion size, the nomogram was able to provide more robust predictions for early death in ovarian cancer patients.


Author(s):  
Yajuan Zhao ◽  
Junli Zhang ◽  
Shuhan Wang ◽  
Qianqian Jiang ◽  
Keshu Xu

Background: Hepatocellular carcinoma (HCC) is the world’s second most deadly cancer, and metabolic reprogramming is its distinguishing feature. Among metabolite profiling, variation in amino acid metabolism supports tumor proliferation and metastasis to the most extent, yet a systematic study on the role of amino acid metabolism-related genes in HCC is still lacking. An effective amino acid metabolism-related prediction signature is urgently needed to assess the prognosis of HCC patients for individualized treatment.Materials and Methods: RNA-seq data of HCC from the TCGA-LIHC and GSE14520 (GPL3921) datasets were defined as the training set and validation set, respectively. Amino acid metabolic genes were extracted from the Molecular Signature Database. Univariate Cox and LASSO regression analyses were performed to build a predictive risk signature. K-M curves, ROC curves, and univariate and multivariate Cox regression were conducted to evaluate the predictive value of this risk signature. Functional enrichment was analyzed by GSEA and CIBERSORTx software.Results: A nine-gene amino acid metabolism-related risk signature including B3GAT3, B4GALT2, CYB5R3, GNPDA1, GOT2, HEXB, HMGCS2, PLOD2, and SEPHS1 was constructed to predict the overall survival (OS) of HCC patients. Patients were separated into high-risk and low-risk groups based on risk scores and low-risk patients had lower risk scores and longer survival time. Univariate and multivariate Cox regression verified that this signature was an independent risk factor for HCC. ROC curves showed that this risk signature can effectively predict the 1-, 2-, 3- and 5-year survival times of patients with HCC. Additionally, prognostic nomograms were established based on the training set and validation set. These genes were closely correlated with the immune regulation.Conclusion: Our study identified a nine-gene amino acid metabolism-related risk signature and built predictive nomograms for OS in HCC. These findings will help us to personalize the treatment of liver cancer patients.


2020 ◽  
Author(s):  
Wenbin Shen ◽  
Wei Jiang ◽  
Shuang Ye ◽  
Min Sun ◽  
Huijuan Yang ◽  
...  

Abstract Background Epigenetic factors play a critical role in tumor development and progression. The aim of this study was to construct and validate a robust epigenetic gene-set based signature for predicting prognosis of ovarian cancer (OC). Methods Public microarray data of OC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were identified and patients from TCGA dataset were randomized 3:1 into discovery and internal validation series. GSE14764 and GSE26712 from GEO database were combined as the external validation set. LASSO Cox regression model was performed in the discovery set to filter the most useful prognostic epigenetic factors. Results Based on LASSO Cox regression model, we built a 26 epigenetic factors based prognostic signature. In the discovery set, patients in high risk group showed significantly poorer overall survival than that patients in low risk group (HR: 2.11, 95% CI: 1.65–2.72, P < 0.001). The results were further validated in the internal validation set (HR: 1.69, 95% CI: 1.07–2.63, P = 0.020) and external validation set (HR 1.95, 95% CI 1.41–2.69; p < 0.001). Survival ROC at 5 year suggested that the epigenetic signature (AUC = 0.700) had better prognostic accuracy than any other clinicopathological factors in the entire cohort. In addition, survival decision curve analysis unveiled a considerable value of clinical utility of the epigenetic signature. Conclusions We successfully developed a robust epigenetic signature that can accurately predict prognosis in OC.


2021 ◽  
Author(s):  
Wenxiang Zhang ◽  
Bolun Ai ◽  
Xiangyi Kong ◽  
Xiangyu Wang ◽  
Jie Zhai ◽  
...  

Abstract Background Triple-negative breast cancer (TNBC) is a specific histological type of breast cancer with a poor prognosis, early recurrence, which lacks durable chemotherapy responses and effective targeted therapies. We aimed to construct an accurate prognostic risk model based on homologous recombination deficiency (HRD) - gene expression profiles for improving prognosis prediction of TNBC. Methods Triple-negative breast cancer RNA sequencing data and sample clinical information were downloaded from the breast invasive carcinoma (BRCA) cohort in the Cancer Genome Atlas (TCGA) database. Combined with the HRD database, tumor samples were divided into two sets. We screened differentially expressed genes (DEGs) and then identified HRD-related prognostic genes using weighted gene co-expression network analysis (WGCNA) and Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were used to identifying key prognostic genes. Risk scores were calculated and compared with HRD score, Kaplan–Meier (KM) survival analysis were used to assess its prognostic power. GSE103091 dataset from GEO (Gene Expression Omnibus) database was used to validate the signature. Univariate and multivariate Cox regression were performed to independently verify the prognosis of the risk score. A nomogram was constructed and revealed by time-dependent ROC curves to guide clinical practice. Results We found that HRD tumor samples (HRD score > = 42) in TNBC patients were associated with poor overall survival (p = 0.027). We identified a total of 147 differential genes including 203 up-regulated and 213 down-regulated genes, among which 29 were prognosis-related genes. Through the LASSO method, 6 key prognostic genes ((MUCL1, IVL, FAM46C, CHI3L1, PRR15L, and CLEC3A) were selected and a 6-gene risk score was constructed. We found risk score was negatively associated with homologous recombination deficiency (HRD) scores (r = -0.22, p = 0.019). Compared with the low-risk group, Kaplan-Meier survival analysis shows that the high-risk group has an obvious poorer prognosis (P < 0.0001). Finally, we integrated the risk score model and clinical factors of TNBC (AJCC-stage, HRD score, T stage, and N stage) to construct a compound nomogram. Time-dependent ROC curves showed the risk score performed better in 1-, 3- and 5-year survival predictions compared with AJCC-stage. Conclusions Based on HRD gene expression data, our six HRD-related gene signature and nomogram could be practical and reliable tools for predicting OS in patients with TNBC.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Jing Cao ◽  
Jiao Gong ◽  
Christ-Jonathan Tsia Hin Fong ◽  
Cuicui Xiao ◽  
Guoli Lin ◽  
...  

Background. Prediction of HBsAg seroclearance, defined as the loss of circulating HBsAg with or without development of antibodies for HBsAg in patients with chronic hepatitis B (CHB), is highly difficult and challenging due to its low incidence. This study is aimed at developing and validating a nomogram for prediction of HBsAg loss in CHB patients. Methods. We analyzed a total of 1398 patients with CHB. Two-thirds of the patients were randomly assigned to the training set (n=918), and one-third were assigned to the validation set (n=480). Univariate and multivariate analysis by Cox regression analysis was performed using the training set, and the nomogram was constructed. Discrimination and calibration were performed using the training set and validation set. Results. On multivariate analysis of the training set, independent factors for HBsAg loss including BMI, HBeAg status, HBsAg titer (quantitative HBsAg), and baseline hepatitis B virus (HBV) DNA level were incorporated into the nomogram. The HBsAg seroclearance calibration curve showed an optimal agreement between predictions by the nomogram and actual observation. The concordance index (C-index) of nomogram was 0.913, with confirmation in the validation set where the C-index was 0.886. Conclusions. We established and validated a novel nomogram that can individually predict HBsAg seroclearance and non-seroclearance for CHB patients, which is clinically unprecedented. This practical prognostic model may help clinicians in decision-making and design of clinical studies.


2019 ◽  
Vol 31 (5) ◽  
pp. 665-673 ◽  
Author(s):  
Maud Menard ◽  
Alexis Lecoindre ◽  
Jean-Luc Cadoré ◽  
Michèle Chevallier ◽  
Aurélie Pagnon ◽  
...  

Accurate staging of hepatic fibrosis (HF) is important for treatment and prognosis of canine chronic hepatitis. HF scores are used in human medicine to indirectly stage and monitor HF, decreasing the need for liver biopsy. We developed a canine HF score to screen for moderate or greater HF. We included 96 dogs in our study, including 5 healthy dogs. A liver biopsy for histologic examination and a biochemistry profile were performed on all dogs. The dogs were randomly split into a training set of 58 dogs and a validation set of 38 dogs. A HF score that included alanine aminotransferase, alkaline phosphatase, total bilirubin, potassium, and gamma-glutamyl transferase was developed in the training set. Model performance was confirmed using the internal validation set, and was similar to the performance in the training set. The overall sensitivity and specificity for the study group were 80% and 70% respectively, with an area under the curve of 0.80 (0.71–0.90). This HF score could be used for indirect diagnosis of canine HF when biochemistry panels are performed on the Konelab 30i (Thermo Scientific), using reagents as in our study. External validation is required to determine if the score is sufficiently robust to utilize biochemical results measured in other laboratories with different instruments and methodologies.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fei Li ◽  
Dongcen Ge ◽  
Shu-lan Sun

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Aihua Wu ◽  
Zhigang Liang ◽  
Songbo Yuan ◽  
Shanshan Wang ◽  
Weidong Peng ◽  
...  

BackgroundThe diagnostic value of clinical and laboratory features to differentiate between malignant pleural effusion (MPE) and benign pleural effusion (BPE) has not yet been established.ObjectivesThe present study aimed to develop and validate the diagnostic accuracy of a scoring system based on a nomogram to distinguish MPE from BPE.MethodsA total of 1,239 eligible patients with PE were recruited in this study and randomly divided into a training set and an internal validation set at a ratio of 7:3. Logistic regression analysis was performed in the training set, and a nomogram was developed using selected predictors. The diagnostic accuracy of an innovative scoring system based on the nomogram was established and validated in the training, internal validation, and external validation sets (n = 217). The discriminatory power and the calibration and clinical values of the prediction model were evaluated.ResultsSeven variables [effusion carcinoembryonic antigen (CEA), effusion adenosine deaminase (ADA), erythrocyte sedimentation rate (ESR), PE/serum CEA ratio (CEA ratio), effusion carbohydrate antigen 19-9 (CA19-9), effusion cytokeratin 19 fragment (CYFRA 21-1), and serum lactate dehydrogenase (LDH)/effusion ADA ratio (cancer ratio, CR)] were validated and used to develop a nomogram. The prediction model showed both good discrimination and calibration capabilities for all sets. A scoring system was established based on the nomogram scores to distinguish MPE from BPE. The scoring system showed favorable diagnostic performance in the training set [area under the curve (AUC) = 0.955, 95% confidence interval (CI) = 0.942–0.968], the internal validation set (AUC = 0.952, 95% CI = 0.932–0.973), and the external validation set (AUC = 0.973, 95% CI = 0.956–0.990). In addition, the scoring system achieved satisfactory discriminative abilities at separating lung cancer-associated MPE from tuberculous pleurisy effusion (TPE) in the combined training and validation sets.ConclusionsThe present study developed and validated a scoring system based on seven parameters. The scoring system exhibited a reliable diagnostic performance in distinguishing MPE from BPE and might guide clinical decision-making.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zixuan Song ◽  
Yangzi Zhou ◽  
Xue Bai ◽  
Dandan Zhang

Background: Ovarian cancer is a common gynecological malignancy, most of which is epithelial ovarian cancer (EOC). Advanced EOC is linked with a higher incidence of premature death. To date, no effective prognostic tools are available to evaluate the possibility of early death in patients with advanced EOC.Methods: Advanced (FIGO stage III and IV) EOC patients who were enrolled in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were regarded as subjects and studied. We aimed to construct a nomogram that can deliver early death prognosis in patients with advanced EOC by identifying crucial independent factors using univariate and multivariate logistic regression analyses to help deliver accurate prognoses.Results: In total, 13,403 patients with advanced EOC were included in this study. Three hundred ninety-seven out of a total of 9,379 FIGO stage III patients died early. There were 4,024 patients with FIGO stage IV, 414 of whom died early. Nomograms based on independent prognostic factors have the satisfactory predictive capability and clinical pragmatism. The internal validation feature of the nomogram demonstrated a high level of accuracy of the predicted death.Conclusions: By analyzing data from a large cohort, a clinically convenient nomogram was established to predict premature death in advanced EOC. This tool can aid clinicians in screening patients who are at higher risk for tailoring treatment plans.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Wei Ma ◽  
Fangkun Zhao ◽  
Xinmiao Yu ◽  
Shu Guan ◽  
Huandan Suo ◽  
...  

Abstract Background Breast cancer is a highly heterogeneous disease, this poses challenges for classification and management. Long non-coding RNAs play acrucial role in the breast cancersdevelopment and progression, especially in tumor-related immune processes which have become the most rapidly investigated area. Therefore, we aimed at developing an immune-related lncRNA signature to improve the prognosis prediction of breast cancer. Methods We obtained breast cancer patient samples and corresponding clinical data from The Cancer Genome Atlas (TCGA) database. Immune-related lncRNAs were screened by co-expression analysis of immune-related genes which were downloaded from the Immunology Database and Analysis Portal (ImmPort). Clinical patient samples were randomly separated into training and testing sets. In the training set, univariate Cox regression analysis and LASSO regression were utilized to build a prognostic immune-related lncRNA signature. The signature was validated in the training set, testing set, and whole cohorts by the Kaplan–Meier log-rank test, time-dependent ROC curve analysis, principal component analysis, univariate andmultivariate Cox regression analyses. Results A total of 937 immune- related lncRNAs were identified, 15 candidate immune-related lncRNAs were significantly associated with overall survival (OS). Eight of these lncRNAs (OTUD6B-AS1, AL122010.1, AC136475.2, AL161646.1, AC245297.3, LINC00578, LINC01871, AP000442.2) were selected for establishment of the risk prediction model. The OS of patients in the low-risk group was higher than that of patients in the high-risk group (p = 1.215e − 06 in the training set; p = 0.0069 in the validation set; p = 1.233e − 07 in whole cohort). The time-dependent ROC curve analysis revealed that the AUCs for OS in the first, eighth, and tenth year were 0.812, 0.81, and 0.857, respectively, in the training set, 0.615, 0.68, 0.655 in the validation set, and 0.725, 0.742, 0.741 in the total cohort. Multivariate Cox regression analysis indicated the model was a reliable and independent indicator for the prognosis of breast cancer in the training set (HR = 1.432; 95% CI 1.204–1.702, p < 0.001), validation set (HR = 1.162; 95% CI 1.004–1.345, p = 0.044), and whole set (HR = 1.240; 95% CI 1.128–1.362, p < 0.001). GSEA analysis revealed a strong connection between the signature and immune-related biological processes and pathways. Conclusions We constructed and verified a robust signature of 8 immune-related lncRNAs for the prediction of breast cancer patient survival.


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