A three‐microRNA signature identifies two subtypes of glioblastoma patients with different clinical outcomes
Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults, characterized by aggressive growth, limited response to therapy, and inexorable recurrence. Because of the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and th...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-09-01
|
| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12047 |
| _version_ | 1828118413216579584 |
|---|---|
| author | Giovanna Marziali Mariachiara Buccarelli Alessandro Giuliani Ramona Ilari Sveva Grande Alessandra Palma Quintino G. D'Alessandris Maurizio Martini Mauro Biffoni Roberto Pallini Lucia Ricci‐Vitiani |
| author_facet | Giovanna Marziali Mariachiara Buccarelli Alessandro Giuliani Ramona Ilari Sveva Grande Alessandra Palma Quintino G. D'Alessandris Maurizio Martini Mauro Biffoni Roberto Pallini Lucia Ricci‐Vitiani |
| author_sort | Giovanna Marziali |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults, characterized by aggressive growth, limited response to therapy, and inexorable recurrence. Because of the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and therapeutic strategies based on biologically and clinically relevant patient stratification systems. Analyzing a collection of patient‐derived GBM stem‐like cells (GSCs) by gene expression profiling, nuclear magnetic resonance spectroscopy, and signal transduction pathway activation, we identified two GSC clusters characterized by different clinical features. Due to the widely documented role played by microRNAs (miRNAs) in the tumorigenesis process, in this study we explored whether these two GBM patient subtypes could also be discriminated by different miRNA signatures. Global miRNA expression pattern was analyzed by oblique principal component analysis and principal component analysis. By a combined inferential strategy on PCA results, we identified a reduced set of three miRNAs – miR‐23a, miR‐27a, and miR‐9* (miR‐9‐3p) – able to discriminate the proneural‐ and mesenchymal‐like GSC phenotypes as well as mesenchymal and proneural subtypes of primary GBM included in The Cancer Genome Atlas (TCGA) data set. Kaplan–Meier analysis showed a significant correlation between the selected miRNAs and overall survival in 429 GBM specimens from TCGA‐identifying patients who had an unfavorable outcome. The survival prognostic capability of the three‐miRNA signatures could have important implications for the understanding of the biology of GBM subtypes and could be useful in patient stratification to facilitate interpretation of results from clinical trials. |
| first_indexed | 2024-04-11T13:31:45Z |
| format | Article |
| id | doaj.art-0a53b4e86ece46a5a82f78fa7fc44eb1 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-04-11T13:31:45Z |
| publishDate | 2017-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-0a53b4e86ece46a5a82f78fa7fc44eb12022-12-22T04:21:47ZengWileyMolecular Oncology1574-78911878-02612017-09-011191115112910.1002/1878-0261.12047A three‐microRNA signature identifies two subtypes of glioblastoma patients with different clinical outcomesGiovanna Marziali0Mariachiara Buccarelli1Alessandro Giuliani2Ramona Ilari3Sveva Grande4Alessandra Palma5Quintino G. D'Alessandris6Maurizio Martini7Mauro Biffoni8Roberto Pallini9Lucia Ricci‐Vitiani10Department of Hematology, Oncology and Molecular Medicine Istituto Superiore di Sanità Rome ItalyDepartment of Hematology, Oncology and Molecular Medicine Istituto Superiore di Sanità Rome ItalyDepartment of Environment and Health Istituto Superiore di Sanità Rome ItalyDepartment of Hematology, Oncology and Molecular Medicine Istituto Superiore di Sanità Rome ItalyDepartment of Technology and Health Istituto Superiore di Sanità Rome ItalyDepartment of Technology and Health Istituto Superiore di Sanità Rome ItalyInstitute of Neurosurgery Università Cattolica del Sacro Cuore Rome ItalyInstitute of Pathology Università Cattolica del Sacro Cuore Rome ItalyDepartment of Hematology, Oncology and Molecular Medicine Istituto Superiore di Sanità Rome ItalyInstitute of Neurosurgery Università Cattolica del Sacro Cuore Rome ItalyDepartment of Hematology, Oncology and Molecular Medicine Istituto Superiore di Sanità Rome ItalyGlioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults, characterized by aggressive growth, limited response to therapy, and inexorable recurrence. Because of the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and therapeutic strategies based on biologically and clinically relevant patient stratification systems. Analyzing a collection of patient‐derived GBM stem‐like cells (GSCs) by gene expression profiling, nuclear magnetic resonance spectroscopy, and signal transduction pathway activation, we identified two GSC clusters characterized by different clinical features. Due to the widely documented role played by microRNAs (miRNAs) in the tumorigenesis process, in this study we explored whether these two GBM patient subtypes could also be discriminated by different miRNA signatures. Global miRNA expression pattern was analyzed by oblique principal component analysis and principal component analysis. By a combined inferential strategy on PCA results, we identified a reduced set of three miRNAs – miR‐23a, miR‐27a, and miR‐9* (miR‐9‐3p) – able to discriminate the proneural‐ and mesenchymal‐like GSC phenotypes as well as mesenchymal and proneural subtypes of primary GBM included in The Cancer Genome Atlas (TCGA) data set. Kaplan–Meier analysis showed a significant correlation between the selected miRNAs and overall survival in 429 GBM specimens from TCGA‐identifying patients who had an unfavorable outcome. The survival prognostic capability of the three‐miRNA signatures could have important implications for the understanding of the biology of GBM subtypes and could be useful in patient stratification to facilitate interpretation of results from clinical trials.https://doi.org/10.1002/1878-0261.12047glioblastomaglioblastoma stem‐like cellsmicroRNAspatient stratification |
| spellingShingle | Giovanna Marziali Mariachiara Buccarelli Alessandro Giuliani Ramona Ilari Sveva Grande Alessandra Palma Quintino G. D'Alessandris Maurizio Martini Mauro Biffoni Roberto Pallini Lucia Ricci‐Vitiani A three‐microRNA signature identifies two subtypes of glioblastoma patients with different clinical outcomes Molecular Oncology glioblastoma glioblastoma stem‐like cells microRNAs patient stratification |
| title | A three‐microRNA signature identifies two subtypes of glioblastoma patients with different clinical outcomes |
| title_full | A three‐microRNA signature identifies two subtypes of glioblastoma patients with different clinical outcomes |
| title_fullStr | A three‐microRNA signature identifies two subtypes of glioblastoma patients with different clinical outcomes |
| title_full_unstemmed | A three‐microRNA signature identifies two subtypes of glioblastoma patients with different clinical outcomes |
| title_short | A three‐microRNA signature identifies two subtypes of glioblastoma patients with different clinical outcomes |
| title_sort | three microrna signature identifies two subtypes of glioblastoma patients with different clinical outcomes |
| topic | glioblastoma glioblastoma stem‐like cells microRNAs patient stratification |
| url | https://doi.org/10.1002/1878-0261.12047 |
| work_keys_str_mv | AT giovannamarziali athreemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT mariachiarabuccarelli athreemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT alessandrogiuliani athreemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT ramonailari athreemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT svevagrande athreemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT alessandrapalma athreemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT quintinogdalessandris athreemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT mauriziomartini athreemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT maurobiffoni athreemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT robertopallini athreemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT luciariccivitiani athreemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT giovannamarziali threemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT mariachiarabuccarelli threemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT alessandrogiuliani threemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT ramonailari threemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT svevagrande threemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT alessandrapalma threemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT quintinogdalessandris threemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT mauriziomartini threemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT maurobiffoni threemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT robertopallini threemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes AT luciariccivitiani threemicrornasignatureidentifiestwosubtypesofglioblastomapatientswithdifferentclinicaloutcomes |