Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based prognostic model for distant metastasis
Abstract Background Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer, with diverse molecular characteristics and clinical outcomes. This study aims to dissect the molecular heterogeneity of NPC, followed by the construction of a microRNA (miRNA)-based prognostic model for pr...
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12929-018-0417-5 |
| _version_ | 1818194207546802176 |
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| author | Lan Zhao Alvin H. W. Fong Na Liu William C. S. Cho |
| author_facet | Lan Zhao Alvin H. W. Fong Na Liu William C. S. Cho |
| author_sort | Lan Zhao |
| collection | DOAJ |
| description | Abstract Background Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer, with diverse molecular characteristics and clinical outcomes. This study aims to dissect the molecular heterogeneity of NPC, followed by the construction of a microRNA (miRNA)-based prognostic model for prediction of distant metastasis. Methods We retrieved two NPC datasets: GSE32960 and GSE70970 as training and validation cohorts, respectively. Consensus clustering was employed for cluster discovery, and support vector machine was used to build a classifier. Finally, Cox regression analysis was applied to constructing a prognostic model for predicting risk of distant metastasis. Results Three NPC subtypes (immunogenic, classical and mesenchymal) were identified that are molecularly distinct and clinically relevant, of which mesenchymal subtype (~ 36%) is associated with poor prognosis, characterized by suppressing tumor suppressor miRNAs and the activation of epithelial-mesenchymal transition. Out of the 25 most differentially expressed miRNAs in mesenchymal subtype, miR-142, miR-26a, miR-141 and let-7i have significant prognostic power (P < 0.05). Conclusions We proposed for the first time that NPC can be stratified into three subtypes. Using a panel of 4 miRNAs, we established a prognostic model that can robustly stratify NPC patients into high- and low- risk groups of distant metastasis. |
| first_indexed | 2024-12-12T00:58:37Z |
| format | Article |
| id | doaj.art-94096f7d68a34cf8bf09c79da486861f |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-12-12T00:58:37Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-94096f7d68a34cf8bf09c79da486861f2022-12-22T00:43:48ZengBMCJournal of Biomedical Science1423-01272018-02-0125111210.1186/s12929-018-0417-5Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based prognostic model for distant metastasisLan Zhao0Alvin H. W. Fong1Na Liu2William C. S. Cho3Department of Electronic Engineering, City University of Hong KongDepartment of Clinical Oncology, Queen Elizabeth HospitalState Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer CenterDepartment of Clinical Oncology, Queen Elizabeth HospitalAbstract Background Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer, with diverse molecular characteristics and clinical outcomes. This study aims to dissect the molecular heterogeneity of NPC, followed by the construction of a microRNA (miRNA)-based prognostic model for prediction of distant metastasis. Methods We retrieved two NPC datasets: GSE32960 and GSE70970 as training and validation cohorts, respectively. Consensus clustering was employed for cluster discovery, and support vector machine was used to build a classifier. Finally, Cox regression analysis was applied to constructing a prognostic model for predicting risk of distant metastasis. Results Three NPC subtypes (immunogenic, classical and mesenchymal) were identified that are molecularly distinct and clinically relevant, of which mesenchymal subtype (~ 36%) is associated with poor prognosis, characterized by suppressing tumor suppressor miRNAs and the activation of epithelial-mesenchymal transition. Out of the 25 most differentially expressed miRNAs in mesenchymal subtype, miR-142, miR-26a, miR-141 and let-7i have significant prognostic power (P < 0.05). Conclusions We proposed for the first time that NPC can be stratified into three subtypes. Using a panel of 4 miRNAs, we established a prognostic model that can robustly stratify NPC patients into high- and low- risk groups of distant metastasis.http://link.springer.com/article/10.1186/s12929-018-0417-5Nasopharyngeal carcinomaMolecular subtypingConsensus clusteringmicroRNADistant metastasisCox regression model |
| spellingShingle | Lan Zhao Alvin H. W. Fong Na Liu William C. S. Cho Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based prognostic model for distant metastasis Journal of Biomedical Science Nasopharyngeal carcinoma Molecular subtyping Consensus clustering microRNA Distant metastasis Cox regression model |
| title | Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based prognostic model for distant metastasis |
| title_full | Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based prognostic model for distant metastasis |
| title_fullStr | Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based prognostic model for distant metastasis |
| title_full_unstemmed | Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based prognostic model for distant metastasis |
| title_short | Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based prognostic model for distant metastasis |
| title_sort | molecular subtyping of nasopharyngeal carcinoma npc and a microrna based prognostic model for distant metastasis |
| topic | Nasopharyngeal carcinoma Molecular subtyping Consensus clustering microRNA Distant metastasis Cox regression model |
| url | http://link.springer.com/article/10.1186/s12929-018-0417-5 |
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