scholarly journals A genomic-clinicopathologic nomogram predict survival for patients with laryngeal squamous cell carcinoma

2019 ◽  
Author(s):  
Jie Cui ◽  
Qingquan Wen ◽  
Xiaojun Tan ◽  
Jinsong Piao ◽  
Qiong Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Calibration Curve ◽  
Survival Probability ◽  
Area Under Curve ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Cox Regression ◽  
Curve Analysis ◽  
Tnm Stage ◽  
Decision Curve Analysis

Abstract Long non-coding RNAs (lncRNAs), which have little or no ability to encode proteins, have attracted special attention due to their potential role in cancer disease. We aimed to establish a lncRNAs signature and a nomogram incorporating the genomic and clinicopathologic factors to improve the accuracy of survival prediction for laryngeal squamous cell carcinoma (LSCC). LSCC RNA sequencing (RNA-seq) data set and the matched clinicopathologic information were downloaded from the Cancer Genome Atlas (TCGA). Using univariable Cox regression and Least absolute shrinkage and selection operator (LASSO) analysis, we developed a thirteen lncRNAs signature related to prognosis. On the basis of multivariable Cox regression analysis results, a nomogram integrating the genomic and clinicopathologic predictors was built. The predictive accuracy and discriminative ability of the inclusive nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was conducted to assess clinical value of our nomogram. Consequently, thirteen overall survival (OS) -related lncRNAs were identified, and the signature consisting of the selected thirteen lncRNAs could effectively divide patients into high-risk and low-risk subgroup, with the area under curve (AUC) of 0.89 (3-year OS) and AUC of 0.885(5-year OS). Independent factors derived from multivariable analysis to predict survival were margin status, tumor status and lncRNAs signature, which were all assembled into the nomogram. The calibration curve for the survival probability showed that the predictions based on the nomogram were in good coincide with actual observations. The C-index of the nomogram was 0.82 (0.77-0.87), and the area under curve (AUC) of nomogram in predicting overall survival (OS) was 0.938, which were significantly higher than traditional TNM stage. Decision curve analysis further demonstrated that our nomogram had larger net benefit than TNM stage. In summary, an inclusive nomogram for patients with LSCC, comprising genomic and clinicopathologic variables, generates more accurate estimations of the survival probability when compared TNM stage alone, but more additional data remains needed before being used in clinical practice.

scholarly journals A Genomic-Clinicopathologic Nomogram Predicts Survival for Patients with Laryngeal Squamous Cell Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Jie Cui ◽  
Qingquan Wen ◽  
Xiaojun Tan ◽  
Zhen Chen ◽  
Genglong Liu
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Calibration Curve ◽  
Survival Probability ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Cox Regression ◽  
Curve Analysis ◽  
Tnm Stage ◽  
Decision Curve Analysis

Background. Long noncoding RNAs (lncRNAs), which have little or no ability to encode proteins, have attracted special attention due to their potential role in cancer disease. We aimed to establish a lncRNA signature and a nomogram incorporating the genomic and clinicopathologic factors to improve the accuracy of survival prediction for laryngeal squamous cell carcinoma (LSCC). Methods. A LSCC RNA-sequencing (RNA-seq) dataset and the matched clinicopathologic information were downloaded from The Cancer Genome Atlas (TCGA). Using univariable Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, we developed a thirteen-lncRNA signature related to prognosis. On the basis of multivariable Cox regression analysis results, a nomogram integrating the genomic and clinicopathologic predictors was built. The predictive accuracy and discriminative ability of the inclusive nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with the TNM staging system by C-index and receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was conducted to evaluate the clinical value of our nomogram. Results. Thirteen overall survival- (OS-) related lncRNAs were identified, and the signature consisting of the selected thirteen lncRNAs could effectively divide patients into high-risk and low-risk subgroups, with area under curves (AUC) of 0.89 (3-year OS) and 0.885 (5-year OS). Independent factors derived from multivariable analysis to predict survival were margin status, tumor status, and lncRNA signature, which were all assembled into the nomogram. The calibration curve for the survival probability showed that the predictions based on the nomogram coincided well with actual observations. The C-index of the nomogram was 0.82 (0.77-0.87), and the area under curve (AUC) of the nomogram in predicting overall survival (OS) was 0.938, both of which were significantly higher than the traditional TNM stage. Decision curve analysis further demonstrated that our nomogram had larger net benefit than TNM stage. Conclusion. An inclusive nomogram for patients with LSCC, comprising genomic and clinicopathologic variables, generates more accurate estimations of the survival probability when compared with TNM stage alone, but more data are needed before the nomogram is used in clinical practice.

scholarly journals Development and validation of nomogram to predict risk of survival in patients with laryngeal squamous cell carcinoma

2020 ◽  
Author(s):  
Jie Cui ◽  
Liping Wang ◽  
Waisheng Zhong ◽  
zhen chen ◽  
Xiaojun Tan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Calibration Curve ◽  
Survival Probability ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Curve Analysis ◽  
Tnm Stage ◽  
Decision Curve Analysis ◽  
Cox Regression Analysis

Abstract Background: Due to a wide variation of tumor behavior, prediction of survival in laryngeal squamous cell carcinoma (LSCC) patients received curative-intend surgery is an important but formidable challenge. We attempted to establish a nomogram to precisely predict survival probability in LSCC patients. Methods: A total of 369 consecutive LSCC patients underwent curative resection between 2008 and 2012 at Hunan Province Cancer Hospital were included in this study. Subsequently, 369 LSCC patients were assigned to a training set (N=261) and a validation set (N=108) at random. On the basis of multivariable Cox regression analysis results, we developed a nomogram. The predictive accuracy and discriminative ability of the nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was conducted to estimate clinical usefulness of our nomogram. Results: Six independent parameters to predict prognosis were age, pack years, N-stage, lymph node ratio (LNR), anemia and albumin, which were all assembled into the nomogram. The calibration curve verified excellent models’ concordance. The C-index of the nomogram was 0.73 (0.68-0.78), and the area under curve (AUC) of nomogram in predicting overall survival (OS) were 0.766, which were significantly higher than traditional TNM stage. Decision curve analysis further demonstrated that our nomogram had larger net benefit than TNM stage.Conclusion: A risk prediction nomogram for patients with LSCC, incorporating easily assessable clinicopathologic factors, generates more precise estimations of the survival probability when compared TNM stage alone, but still need additional data before being used in clinical application.

scholarly journals An integrated nomogram combining lncRNAs classifier and clinicopathologic factors to predict the recurrence of head and neck squamous cell carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jie Cui ◽  
Qingquan Wen ◽  
Xiaojun Tan ◽  
Jinsong Piao ◽  
Qiong Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Calibration Curve ◽  
Cox Regression ◽  
Curve Analysis ◽  
Tnm Stage ◽  
Decision Curve Analysis ◽  
Clinicopathologic Factors

AbstractLong non-coding RNAs (lncRNAs) which have little or no protein-coding capacity, due to their potential roles in the cancer disease, caught a particular interest. Our study aims to develop an lncRNAs-based classifier and a nomogram incorporating the lncRNAs classifier and clinicopathologic factors to help to improve the accuracy of recurrence prediction for head and neck squamous cell carcinoma (HNSCC) patients. The HNSCC lncRNAs profiling data and the corresponding clinicopathologic information were downloaded from TANRIC database and cBioPortal. Using univariable Cox regression and Least absolute shrinkage and selection operator (LASSO) analysis, we developed 15-lncRNAs-based classifier related to recurrence. On the basis of multivariable Cox regression analysis results, a nomogram integrating the genomic and clinicopathologic predictors was built. The predictive accuracy and discriminative ability of the inclusive nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was conducted to evaluate clinical value of our nomogram. Consequently, fifteen recurrence-free survival (RFS) -related lncRNAs were identified, and the classifier consisting of the established 15 lncRNAs could effectively divide patients into high-risk and low-risk subgroup. The prediction ability of the 15-lncRNAs-based classifier for predicting 3- year and 5-year RFS were 0.833 and 0.771. Independent factors derived from multivariable analysis to predict recurrence were number of positive LNs, margin status, mutation count and lncRNAs classifier, which were all embedded into the nomogram. The calibration curve for the recurrence probability showed that the predictions based on the nomogram were in good coincide with practical observations. The C-index of the nomogram was 0.76 (0.72–0.79), and the area under curve (AUC) of nomogram in predicting RFS was 0.809, which were significantly higher than traditional TNM stage and 15-lncRNAs-based classifier. Decision curve analysis further demonstrated that our nomogram had larger net benefit than TNM stage and 15-lncRNAs-based classifier. The results were confirmed externally. In summary, a visually inclusive nomogram for patients with HNSCC, comprising genomic and clinicopathologic variables, generates more accurate prediction of the recurrence probability when compared TNM stage alone, but more additional data remains needed before being used in clinical practice.

scholarly journals Development and validation of nomogram to predict risk of survival in patients with laryngeal squamous cell carcinoma

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Jie Cui ◽  
Liping Wang ◽  
Waisheng Zhong ◽  
Zhen Chen ◽  
Xiaojun Tan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Prediction ◽  
Clinical Application ◽  
Calibration Curve ◽  
Survival Probability ◽  
Additional Data ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Tnm Stage ◽  
Clinicopathologic Factors

Abstract To the best of our knowledge, this is the first study established a nomogram to predict survival probability in Asian patients with LSCC. A risk prediction nomogram for patients with LSCC, incorporating easily assessable clinicopathologic factors, generates more precise estimations of the survival probability when compared TNM stage alone, but still need additional data before being used in clinical application. Background: Due to a wide variation of tumor behavior, prediction of survival in laryngeal squamous cell carcinoma (LSCC) patients received curative-intent surgery is an important but formidable challenge. We attempted to establish a nomogram to precisely predict survival probability in LSCC patients. Methods: A total of 369 consecutive LSCC patients underwent curative resection between 2008 and 2012 at Hunan Province Cancer Hospital were included in the present study. Subsequently, 369 LSCC patients were assigned to a training set (N=261) and a validation set (N=108) at random. On the basis of multivariable Cox regression analysis results, we developed a nomogram. The predictive accuracy and discriminative ability of the nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Results: Six independent parameters to predict prognosis were age, pack years, N-stage, lymph node ratio (LNR), anemia and albumin, which were all assembled into the nomogram. The calibration curve verified excellent models’ concordance. The C-index of the nomogram was 0.73 (0.68–0.78), and the area under curve (AUC) of nomogram in predicting overall survival (OS) was 0.766, which were significantly higher than traditional TNM stage. Decision curve analysis further demonstrated that our nomogram had a larger net benefit than the TNM stage. Conclusion: A risk prediction nomogram for patients with LSCC, incorporating easily assessable clinicopathologic factors, generates more precise estimations of the survival probability when compared TNM stage alone, but still need additional data before being used in clinical application.

scholarly journals Dynamic nomograms combining N classification with ratio-based nodal classifications to predict long-term survival for patients with lung adenocarcinoma after surgery: a SEER population-based study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Suyu Wang ◽  
Yue Yu ◽  
Wenting Xu ◽  
Xin Lv ◽  
Yufeng Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
External Validation ◽  
Predictive Performance ◽  
Information Criterion ◽  
Curve Analysis ◽  
Tnm Stage ◽  
Concordance Index ◽  
Cancer Specific Survival ◽  
Decision Curve Analysis

Abstract Background The prognostic roles of three lymph node classifications, number of positive lymph nodes (NPLN), log odds of positive lymph nodes (LODDS), and lymph node ratio (LNR) in lung adenocarcinoma are unclear. We aim to find the classification with the strongest predictive power and combine it with the American Joint Committee on Cancer (AJCC) 8th TNM stage to establish an optimal prognostic nomogram. Methods 25,005 patients with T1-4N0–2M0 lung adenocarcinoma after surgery between 2004 to 2016 from the Surveillance, Epidemiology, and End Results database were included. The study cohort was divided into training cohort (13,551 patients) and external validation cohort (11,454 patients) according to different geographic region. Univariate and multivariate Cox regression analyses were performed on the training cohort to evaluate the predictive performance of NPLN (Model 1), LODDS (Model 2), LNR (Model 3) or LODDS+LNR (Model 4) respectively for cancer-specific survival and overall survival. Likelihood-ratio χ2 test, Akaike Information Criterion, Harrell concordance index, integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to evaluate the predictive performance of the models. Nomograms were established according to the optimal models. They’re put into internal validation using bootstrapping technique and external validation using calibration curves. Nomograms were compared with AJCC 8th TNM stage using decision curve analysis. Results NPLN, LODDS and LNR were independent prognostic factors for cancer-specific survival and overall survival. LODDS+LNR (Model 4) demonstrated the highest Likelihood-ratio χ2 test, highest Harrell concordance index, and lowest Akaike Information Criterion, and IDI and NRI values suggested Model 4 had better prediction accuracy than other models. Internal and external validations showed that the nomograms combining TNM stage with LODDS+LNR were convincingly precise. Decision curve analysis suggested the nomograms performed better than AJCC 8th TNM stage in clinical practicability. Conclusions We constructed online nomograms for cancer-specific survival and overall survival of lung adenocarcinoma patients after surgery, which may facilitate doctors to provide highly individualized therapy.

scholarly journals Prognostic nomogram for predicting 5-year overall survival in Chinese patients with high-grade osteosarcoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhihong Yao ◽  
Zunxian Tan ◽  
Jifei Yang ◽  
Yihao Yang ◽  
Cao Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Calibration Curve ◽  
Curve Analysis ◽  
Cox Proportional Hazards Model ◽  
Chinese Patients ◽  
Gamma Glutamyl Transferase ◽  
High Grade ◽  
Decision Curve Analysis ◽  
High Grade Osteosarcoma ◽  
Glutamyl Transferase

AbstractThis study aimed to construct a widely accepted prognostic nomogram in Chinese high-grade osteosarcoma (HOS) patients aged ≤ 30 years to provide insight into predicting 5-year overall survival (OS). Data from 503 consecutive HOS patients at our centre between 12/2012 and 05/2019 were retrospectively collected. Eighty-four clinical features and routine laboratory haematological and biochemical testing indicators of each patient at the time of diagnosis were collected. A prognostic nomogram model for predicting OS was constructed based on the Cox proportional hazards model. The performance was assessed by the concordance index (C-index), receiver operating characteristic curve and calibration curve. The utility was evaluated by decision curve analysis. The 5-year OS was 52.1% and 2.6% for the nonmetastatic and metastatic patients, respectively. The nomogram included nine important variables based on a multivariate analysis: tumour stage, surgical type, metastasis, preoperative neoadjuvant chemotherapy cycle, postoperative metastasis time, mean corpuscular volume, tumour-specific growth factor, gamma-glutamyl transferase and creatinine. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.795 (range, 0.703–0.887). Moreover, the decision curve analysis curve also demonstrated the clinical benefit of this model. The nomogram provides an individualized risk estimate of the 5-year OS in patients with HOS aged ≤ 30 years in a Chinese population-based cohort.

15-lncRNAs-based classifier-clinicopathologic nomogram improves the prediction of recurrence in patients with hepatocellular carcinoma

2019 ◽  
Author(s):  
Qiong Zhang ◽  
Gang Ning ◽  
Hongye Jiang ◽  
Yanlin Huang ◽  
Jinsong Piao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Decision Making ◽  
Cox Regression ◽  
Curve Analysis ◽  
Tnm Stage ◽  
Training Set ◽  
Decision Curve Analysis ◽  
Clinicopathologic Factors ◽  
Validation Set ◽  
Better Than

Abstract Background: Our study aims to develop an lncRNAs-based classifier and a nomogram incorporating the genomic signature and clinicopathologic factors to help to improve the accuracy of recurrence prediction for hepatocellular carcinoma(HCC) patients.Methods: The lncRNAs profiling data of 374 HCC patients and 50 normal healthy controls were downloaded from the Cancer Genome Atlas (TCGA). Using univariable Cox regression and Least absolute shrinkage and selection operator (LASSO) analysis, we developed 15-lncRNAs-based classifier and compared our classifier to existing six-lncRNAs signature. Besides, a nomogram incorporating the genomic classifier and clinicopathologic factors was also developed. The predictive accuracy and discriminative ability of the genomic-clinicopathologic nomogram were determined by a concordance index (C-index) and calibration curve and were compared with TNM staging system by C-index, receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was performed to estimate clinical value of our nomogram.Results: Fifteen relapse-free survival (RFS) -related lncRNAs were identified and the classifer, consisting of the identified15 lncRNAs, could effectively classify patients into high-risk and low-risk subgroup. The prediction accuracy of the 15-lncRNAs-based classifier for predicting 2- year and 5-year RFS were 0.791 and 0.834 in the training set and 0.684 and 0.747 in the validation set, which was better than the existing six-lncRNAs signature. Moreover, the AUC of genomic-clinicopathologic nomogram in predicting RFS were 0.837 in the training set and 0.753 in the validation set, and the C-index of the genomic-clinicopathologic nomogram was 0.78 (0.72-0.83) in the training set and 0.71 (0.65-0.76) in the validation set, which was better than traditional TNM stage and 15-lncRNAs-based classifier. Decision curve analysis further demonstrated that our nomogram had larger net benefit than TNM stage and 15-lncRNAs-based classifier. Conclusion: Compared to TNM stage, the 15-lncRNAs-based classifier-clinicopathologic nomogram is a more effective and valuable tool to identify HCC recurrence and may aid in clinical decision-making.

scholarly journals A nomogram based on a gene signature for predicting the prognosis of patients with head and neck squamous cell carcinoma

2019 ◽  
Vol 34 (3) ◽  
pp. 309-317
Author(s):  
Bowen Yang ◽  
Lingyu Fu ◽  
Shan Xu ◽  
Jiawen Xiao ◽  
Zhi Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Predictive Model ◽  
Validation Cohort ◽  
Gene Signature ◽  
Curve Analysis ◽  
Decision Curve Analysis

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors. The purpose of this study was to establish and validate a gene-expression-based prognostic signature in non-metastatic patients with HNSCC. Materials and methods: All the patients were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We randomly divided the GSE65858 samples into 70% (training cohort, n = 190) and 30% (internal validation cohort, n = 72). A total of 36 samples collected from the TCGA HNSCC databases were selected as an independent external validation cohort. The oligo package in R was used to normalize the raw data before analysis. Data characteristics were extracted, and a gene signature was built via the least absolute shrinkage and selection operator regression model. The predictive model was developed by multivariable Cox regression analysis. T stage, N stage, human papilloma virus status, and the gene signature were incorporated in this predictive model, which was shown as a nomogram. Calibration and discrimination were performed to assess the performance of the nomogram. The clinical utility of this nomogram was assessed by the decision curve analysis. Results: Overall, 2001 significant messenger RNAs in HNSCC samples were identified compared with normal samples. The gene signature contained seven genes and significantly correlated with overall survival. The gene signature was also significant in subgroup analysis of the primary cohort. The calibration was plotted in the external cohort (C-index 0.90, 95% CI 0.85, 0.95) compared with the training (C-index 0.76, 95% CI 0.73, 0.79) and internal (C-index 0.71, 95% CI 0.66, 0.77) cohorts. In clinic, a decision curve analysis demonstrated that the model including the prognostic gene signature score status was better than that without it. Conclusion: This study developed and validated a predictive model, which can promote the individualized prediction of overall survival in non-metastatic patients with HNSCC.

scholarly journals 15-lncRNA-Based Classifier-Clinicopathologic Nomogram Improves the Prediction of Recurrence in Patients with Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Qiong Zhang ◽  
Gang Ning ◽  
Hongye Jiang ◽  
Yanlin Huang ◽  
Jinsong Piao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Decision Making ◽  
Cox Regression ◽  
Curve Analysis ◽  
Tnm Stage ◽  
Training Set ◽  
Decision Curve Analysis ◽  
Clinicopathologic Factors ◽  
Validation Set ◽  
Better Than

Background. Our study aims to develop a lncRNA-based classifier and a nomogram incorporating the genomic signature and clinicopathologic factors to help to improve the accuracy of recurrence prediction for hepatocellular carcinoma (HCC) patients. Methods. The lncRNA profiling data of 374 HCC patients and 50 normal healthy controls were downloaded from The Cancer Genome Atlas (TCGA). Using univariable Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, we developed a 15-lncRNA-based classifier and compared our classifier to the existing six-lncRNA signature. Besides, a nomogram incorporating the genomic classifier and clinicopathologic factors was also developed. The predictive accuracy and discriminative ability of the genomic-clinicopathologic nomogram were determined by a concordance index (C-index) and calibration curve and were compared with the TNM staging system by the C-index and receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was performed to estimate the clinical value of our nomogram. Results. Fifteen relapse-free survival (RFS-) related lncRNAs were identified, and the classifier, consisting of the identified 15 lncRNAs, could effectively classify patients into the high-risk and low-risk subgroups. The prediction accuracy of the 15-lncRNA-based classifier for predicting 2-year and 5-year RFS was 0.791 and 0.834 in the training set and 0.684 and 0.747 in the validation set, respectively, which was better than the existing six-lncRNA signature. Moreover, the AUC of genomic-clinicopathologic nomogram in predicting RFS were 0.837 in the training set and 0.753 in the validation set, and the C-index of the genomic-clinicopathologic nomogram was 0.78 (0.72-0.83) in the training set and 0.71 (0.65-0.76) in the validation set, which was better than the traditional TNM stage and 15-lncRNA-based classifier. The decision curve analysis further demonstrated that our nomogram had a larger net benefit than the TNM stage and 15-lncRNA-based classifier. The results were confirmed externally. Conclusion. Compared to the TNM stage, the 15-lncRNAs-based classifier-clinicopathologic nomogram is a more effective and valuable tool to identify HCC recurrence and may aid in clinical decision-making.

scholarly journals Identification and validation of methylation-driven genes prognostic signature for recurrence of laryngeal squamous cell carcinoma by integrated bioinformatics analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jie Cui ◽  
Liping Wang ◽  
Waisheng Zhong ◽  
Zhen Chen ◽  
Jie Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Small Molecules ◽  
Cell Carcinoma ◽  
Bioinformatics Analysis ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Cox Regression ◽  
Tnm Stage ◽  
Prognostic Signature

Abstract Background Recurrence remains a major obstacle to long-term survival of laryngeal squamous cell carcinoma (LSCC). We conducted a genome-wide integrated analysis of methylation and the transcriptome to establish methylation-driven genes prognostic signature (MDGPS) to precisely predict recurrence probability and optimize therapeutic strategies for LSCC. Methods LSCC DNA methylation datasets and RNA sequencing (RNA-seq) dataset were acquired from the Cancer Genome Atlas (TCGA). MethylMix was applied to detect DNA methylation-driven genes (MDGs). By univariate and multivariate Cox regression analyses, five genes of DNA MDGs was developed a recurrence-free survival (RFS)-related MDGPS. The predictive accuracy and clinical value of the MDGPS were evaluated by receiver operating characteristic (ROC) and decision curve analysis (DCA), and compared with TNM stage system. Additionally, prognostic value of MDGPS was validated by external Gene Expression Omnibus (GEO) database. According to 5 MDGs, the candidate small molecules for LSCC were screen out by the CMap database. To strengthen the bioinformatics analysis results, 30 pairs of clinical samples were evaluated by digoxigenin-labeled chromogenic in situ hybridization (CISH). Results A total of 88 DNA MDGs were identified, and five RFS-related MDGs (LINC01354, CCDC8, PHYHD1, MAGEB2 and ZNF732) were chosen to construct a MDGPS. The MDGPS can effectively divide patients into high-risk and low-risk group, with the area under curve (AUC) of 0.738 (5-year RFS) and AUC of 0.74 (3-year RFS). Stratification analysis affirmed that the MDGPS was still a significant statistical prognostic model in subsets of patients with different clinical variables. Multivariate Cox regression analysis indicated the efficacy of MDGPS appears independent of other clinicopathological characteristics. In terms of predictive capacity and clinical usefulness, the MDGPS was superior to traditional TNM stage. Additionally, the MDGPS was confirmed in external LSCC cohorts from GEO. CMap matched the 9 most significant small molecules as promising therapeutic drugs to reverse the LSCC gene expression. Finally, CISH analysis in 30 LSCC tissues and paired adjacent normal tissues revealed that MAGEB2 has significantly higher expression of LSCC compared to adjacent non-neoplastic tissues; LINC01354, CCDC8, PHYHD1, and ZNF732 have significantly lower expression of LSCC compared to adjacent non-neoplastic tissues, which were in line with bioinformatics analysis results. Conclusion A MDGPS, with five DNA MDGs, was identified and validated in LSCC patients by combining transcriptome and methylation datasets analysis. Compared TNM stage alone, it generates more accurate estimations of the recurrence prediction and maybe offer novel research directions and prospects for individualized treatment of patients with LSCC.

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