DOI . ORG {
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Title[redir]:
Mutational landscape of nasopharyngeal carcinoma based onĀ targeted next-generation sequencing: implications for predicting clinical outcomes | Molecular Medicine | Full Text
Description:
Background The aim of this study was to draw a comprehensive mutational landscape of nasopharyngeal carcinoma (NPC) tumors and identify the prognostic factors for distant metastasis-free survival (DMFS). Methods A total of forty primary nonkeratinizing NPC patients underwent targeted next-generation sequencing of 450 cancer-relevant genes. Analysis of these sequencing and clinical data was performed comprehensively. Univariate Cox regression analysis and multivariate Lasso-Cox regression analyses were performed to identify factors that predict distant metastasis and construct a risk score model, and seventy percent of patients were randomly selected from among the samples as a validation cohort. A receiver operating characteristic (ROC) curve and Harrellās concordance index (C-index) were used to investigate whether the risk score was superior to the TNM stage in predicting the survival of patients. The survival of patients was determined by KaplanāMeier curves and log-rank tests. Results The twenty most frequently mutated genes were identified, such as KMT2D, CYLD, and TP53 et al. Their mutation frequencies of them were compared with those of the COSMIC database and cBioPortal database. N stage, tumor mutational burden (TMB), PIK3CA, and SF3B1 were identified as predictors to build the risk score model. The risk score model showed a higher AUC and C-index than the TNM stage model, regardless of the training cohort or validation cohort. Moreover, this study found that patients with tumors harboring PI3K/AKT or RAS pathway mutations have worse DMFS than their wild-type counterparts. Conclusions In this study, we drew a mutational landscape of NPC tumors and established a novel four predictor-based prognostic model, which had much better predictive capacity than TNM stage.
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Keywords {š}
article, patients, genes, mutations, google, scholar, cancer, analysis, npc, pathway, fig, stage, sequencing, study, risk, clinical, score, sfb, nasopharyngeal, cas, pikca, carcinoma, shandong, signaling, data, mutational, distant, survival, model, dmfs, mutated, database, gene, tnm, nextgeneration, prognostic, cohort, identified, found, tumors, metastasis, mutation, tumor, information, molecular, zhang, number, validation, including, landscape,
Topics {āļø}
pi3k/akt/mtor interactive pathway distant metastasis-free survival lasso-cox regression analysis tumorālymph nodeāmetastasis multivariate lasso-cox analysis metastasis-free survival kaplanāmeier survival curves tumor mutational burden nf-Īŗb pathway regulators pi3k-akt signaling pathway springer nature identify metastasis-related factors tumor mutation burden ajcc/uicc staging system molecular-based prediction models author information authors gene expression-based signature rap1 signaling pathway additional information publisher' privacy choices/manage cookies low-read depth region predictor-based prognostic model authors scientific editing tumors harboring pi3k/akt study identified cd58-wee2 receiver operating characteristic tumor-related pathway wide mutational diversity kaplanāmeier analysis bmc mapk signaling pathway state privacy rights kaplanāmeier curves national key research nf-Īŗb pathway distant disease based genomic profiling based predict distant metastasis ras signaling pathway nasopharyngeal carcinoma based pi3k/akt pathway incomplete clinical follow x-title plots small sample size single-nucleotide variants breast cancer subtypes sharing risk score output mirna signature identified npc distant metastasis
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headline:Mutational landscape of nasopharyngeal carcinoma based onĀ targeted next-generation sequencing: implications for predicting clinical outcomes
description:The aim of this study was to draw a comprehensive mutational landscape of nasopharyngeal carcinoma (NPC) tumors and identify the prognostic factors for distant metastasis-free survival (DMFS). A total of forty primary nonkeratinizing NPC patients underwent targeted next-generation sequencing of 450 cancer-relevant genes. Analysis of these sequencing and clinical data was performed comprehensively. Univariate Cox regression analysis and multivariate Lasso-Cox regression analyses were performed to identify factors that predict distant metastasis and construct a risk score model, and seventy percent of patients were randomly selected from among the samples as a validation cohort. A receiver operating characteristic (ROC) curve and Harrellās concordance index (C-index) were used to investigate whether the risk score was superior to the TNM stage in predicting the survival of patients. The survival of patients was determined by KaplanāMeier curves and log-rank tests. The twenty most frequently mutated genes were identified, such as KMT2D, CYLD, and TP53 et al. Their mutation frequencies of them were compared with those of the COSMIC database and cBioPortal database. N stage, tumor mutational burden (TMB), PIK3CA, and SF3B1 were identified as predictors to build the risk score model. The risk score model showed a higher AUC and C-index than the TNM stage model, regardless of the training cohort or validation cohort. Moreover, this study found that patients with tumors harboring PI3K/AKT or RAS pathway mutations have worse DMFS than their wild-type counterparts. In this study, we drew a mutational landscape of NPC tumors and established a novel four predictor-based prognostic model, which had much better predictive capacity than TNM stage.
datePublished:2022-05-13T00:00:00Z
dateModified:2022-05-13T00:00:00Z
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Gene
Tumor mutational burden
Risk score
Nasopharyngeal carcinoma
Distant metastasis-free survival
Target next-generation sequencing
Molecular Medicine
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headline:Mutational landscape of nasopharyngeal carcinoma based onĀ targeted next-generation sequencing: implications for predicting clinical outcomes
description:The aim of this study was to draw a comprehensive mutational landscape of nasopharyngeal carcinoma (NPC) tumors and identify the prognostic factors for distant metastasis-free survival (DMFS). A total of forty primary nonkeratinizing NPC patients underwent targeted next-generation sequencing of 450 cancer-relevant genes. Analysis of these sequencing and clinical data was performed comprehensively. Univariate Cox regression analysis and multivariate Lasso-Cox regression analyses were performed to identify factors that predict distant metastasis and construct a risk score model, and seventy percent of patients were randomly selected from among the samples as a validation cohort. A receiver operating characteristic (ROC) curve and Harrellās concordance index (C-index) were used to investigate whether the risk score was superior to the TNM stage in predicting the survival of patients. The survival of patients was determined by KaplanāMeier curves and log-rank tests. The twenty most frequently mutated genes were identified, such as KMT2D, CYLD, and TP53 et al. Their mutation frequencies of them were compared with those of the COSMIC database and cBioPortal database. N stage, tumor mutational burden (TMB), PIK3CA, and SF3B1 were identified as predictors to build the risk score model. The risk score model showed a higher AUC and C-index than the TNM stage model, regardless of the training cohort or validation cohort. Moreover, this study found that patients with tumors harboring PI3K/AKT or RAS pathway mutations have worse DMFS than their wild-type counterparts. In this study, we drew a mutational landscape of NPC tumors and established a novel four predictor-based prognostic model, which had much better predictive capacity than TNM stage.
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Gene
Tumor mutational burden
Risk score
Nasopharyngeal carcinoma
Distant metastasis-free survival
Target next-generation sequencing
Molecular Medicine
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name:Department of Pathology, The 960Th Hospital of PLA, Jinan, China
name:Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
name:Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
name:Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
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