Integrative multi-omics characterization reveals sex differences in glioblastoma
Abstract Background Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with limited treatment modalities and poor prognosis. Recent studies have highlighted the importance of considering sex differences in cancer incidence, prognosis, molecular disparities, and treatment...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Biology of Sex Differences |
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| Online Access: | https://doi.org/10.1186/s13293-024-00601-7 |
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| author | Byunghyun Jang Dayoung Yoon Ji Yoon Lee Jiwon Kim Jisoo Hong Harim Koo Jason K. Sa |
| author_facet | Byunghyun Jang Dayoung Yoon Ji Yoon Lee Jiwon Kim Jisoo Hong Harim Koo Jason K. Sa |
| author_sort | Byunghyun Jang |
| collection | DOAJ |
| description | Abstract Background Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with limited treatment modalities and poor prognosis. Recent studies have highlighted the importance of considering sex differences in cancer incidence, prognosis, molecular disparities, and treatment outcomes across various tumor types, including colorectal adenocarcinoma, lung adenocarcinoma, and GBM. Methods We performed comprehensive analyses of large-scale multi-omics data (genomic, transcriptomic, and proteomic data) from TCGA, GLASS, and CPTAC to investigate the genetic and molecular determinants that contribute to the unique clinical properties of male and female GBM patients. Results Our results revealed several key differences, including enrichments of MGMT promoter methylation, which correlated with increased overall and post-recurrence survival and improved response to chemotherapy in female patients. Moreover, female GBM exhibited a higher degree of genomic instability, including aneuploidy and tumor mutational burden. Integrative proteomic and phosphor-proteomic characterization uncovered sex-specific protein abundance and phosphorylation activities, including EGFR activation in males and SPP1 hyperphosphorylation in female patients. Lastly, the identified sex-specific biomarkers demonstrated prognostic significance, suggesting their potential as therapeutic targets. Conclusions Collectively, our study provides unprecedented insights into the fundamental modulators of tumor progression and clinical outcomes between male and female GBM patients and facilitates sex-specific treatment interventions. Highlights Female GBM patients were characterized by increased MGMT promoter methylation and favorable clinical outcomes compared to male patients. Female GBMs exhibited higher levels of genomic instability, including aneuploidy and TMB. Each sex-specific GBM is characterized by unique pathway dysregulations and molecular subtypes. EGFR activation is prevalent in male patients, while female patients are marked by SPP1 hyperphosphorylation. |
| first_indexed | 2024-04-24T23:11:21Z |
| format | Article |
| id | doaj.art-3d99471a5068453ba5e83a32605f9691 |
| institution | Directory Open Access Journal |
| issn | 2042-6410 |
| language | English |
| last_indexed | 2024-04-24T23:11:21Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj.art-3d99471a5068453ba5e83a32605f96912024-03-17T12:12:02ZengBMCBiology of Sex Differences2042-64102024-03-0115111510.1186/s13293-024-00601-7Integrative multi-omics characterization reveals sex differences in glioblastomaByunghyun Jang0Dayoung Yoon1Ji Yoon Lee2Jiwon Kim3Jisoo Hong4Harim Koo5Jason K. Sa6Department of Biomedical Informatics, Korea University College of MedicineDepartment of Biomedical Informatics, Korea University College of MedicineDepartment of Biomedical Informatics, Korea University College of MedicineDepartment of Biomedical Informatics, Korea University College of MedicineDepartment of Biomedical Informatics, Korea University College of MedicineDepartment of Biomedical Informatics, Korea University College of MedicineDepartment of Biomedical Informatics, Korea University College of MedicineAbstract Background Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with limited treatment modalities and poor prognosis. Recent studies have highlighted the importance of considering sex differences in cancer incidence, prognosis, molecular disparities, and treatment outcomes across various tumor types, including colorectal adenocarcinoma, lung adenocarcinoma, and GBM. Methods We performed comprehensive analyses of large-scale multi-omics data (genomic, transcriptomic, and proteomic data) from TCGA, GLASS, and CPTAC to investigate the genetic and molecular determinants that contribute to the unique clinical properties of male and female GBM patients. Results Our results revealed several key differences, including enrichments of MGMT promoter methylation, which correlated with increased overall and post-recurrence survival and improved response to chemotherapy in female patients. Moreover, female GBM exhibited a higher degree of genomic instability, including aneuploidy and tumor mutational burden. Integrative proteomic and phosphor-proteomic characterization uncovered sex-specific protein abundance and phosphorylation activities, including EGFR activation in males and SPP1 hyperphosphorylation in female patients. Lastly, the identified sex-specific biomarkers demonstrated prognostic significance, suggesting their potential as therapeutic targets. Conclusions Collectively, our study provides unprecedented insights into the fundamental modulators of tumor progression and clinical outcomes between male and female GBM patients and facilitates sex-specific treatment interventions. Highlights Female GBM patients were characterized by increased MGMT promoter methylation and favorable clinical outcomes compared to male patients. Female GBMs exhibited higher levels of genomic instability, including aneuploidy and TMB. Each sex-specific GBM is characterized by unique pathway dysregulations and molecular subtypes. EGFR activation is prevalent in male patients, while female patients are marked by SPP1 hyperphosphorylation.https://doi.org/10.1186/s13293-024-00601-7Multi-omicsGlioblastomaSex-differenceProteomics |
| spellingShingle | Byunghyun Jang Dayoung Yoon Ji Yoon Lee Jiwon Kim Jisoo Hong Harim Koo Jason K. Sa Integrative multi-omics characterization reveals sex differences in glioblastoma Biology of Sex Differences Multi-omics Glioblastoma Sex-difference Proteomics |
| title | Integrative multi-omics characterization reveals sex differences in glioblastoma |
| title_full | Integrative multi-omics characterization reveals sex differences in glioblastoma |
| title_fullStr | Integrative multi-omics characterization reveals sex differences in glioblastoma |
| title_full_unstemmed | Integrative multi-omics characterization reveals sex differences in glioblastoma |
| title_short | Integrative multi-omics characterization reveals sex differences in glioblastoma |
| title_sort | integrative multi omics characterization reveals sex differences in glioblastoma |
| topic | Multi-omics Glioblastoma Sex-difference Proteomics |
| url | https://doi.org/10.1186/s13293-024-00601-7 |
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