A multi-cohort validated OXPHOS signature predicts survival and immune profiles in grade II/III glioma patients
IntroductionGrade II/III gliomas are invasive brain tumors with a high risk of malignant progression and significant clinical heterogeneity, highlighting the urgent need for reliable prognostic biomarkers to guide personalized treatment strategies. This study aimed to investigate the molecular mecha...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1638824/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849412850493161472 |
|---|---|
| author | Jun Mou Min Zhang Fumin Qin Yajie Cui Keyou Xu Baoye Pang Xinyue Li Wanyi Tan Aiqi Yang Yaxin Liu Lingjun Shen Yanting Liu Kai Xu |
| author_facet | Jun Mou Min Zhang Fumin Qin Yajie Cui Keyou Xu Baoye Pang Xinyue Li Wanyi Tan Aiqi Yang Yaxin Liu Lingjun Shen Yanting Liu Kai Xu |
| author_sort | Jun Mou |
| collection | DOAJ |
| description | IntroductionGrade II/III gliomas are invasive brain tumors with a high risk of malignant progression and significant clinical heterogeneity, highlighting the urgent need for reliable prognostic biomarkers to guide personalized treatment strategies. This study aimed to investigate the molecular mechanisms driving glioma progression and to identify potential therapeutic targets.MethodsWe analyzed 200 mitochondrial oxidative phosphorylation (OXPHOS)-related genes in 512 grade II/III glioma samples from The Cancer Genome Atlas (TCGA). Consensus clustering identified two distinct molecular subtypes (C1 and C2). Differentially expressed genes (DEGs) between subtypes were determined using the limma package. The immune cell composition and tumor microenvironment (TME) characteristics were assessed using ESTIMATE, MCPcounter, and CIBERSORT algorithms. Based on prognostic DEGs, we constructed a four-gene prognostic signature (MAOB, IGFBP2, SERPINA1, and LGR6).ResultsThe C2 molecular subtype was associated with poorer prognosis, higher immune scores, and enrichment in tumor-promoting pathways. The four-gene signature demonstrated strong prognostic performance and robustness across multiple independent validation cohorts. Immunohistochemical (IHC) analysis of clinical glioma specimens confirmed elevated protein expression levels of the four genes in tumor tissues.DiscussionOur OXPHOS-associated gene signature provides novel insights into the molecular classification, immune landscape, and prognosis of grade II/III gliomas. These findings lay the foundation for precision oncology and the development of targeted therapeutic interventions. |
| format | Article |
| id | doaj-art-afe5cdb5c59641dc839fc14952cdc96e |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-afe5cdb5c59641dc839fc14952cdc96e2025-08-20T03:34:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16388241638824A multi-cohort validated OXPHOS signature predicts survival and immune profiles in grade II/III glioma patientsJun Mou0Min Zhang1Fumin Qin2Yajie Cui3Keyou Xu4Baoye Pang5Xinyue Li6Wanyi Tan7Aiqi Yang8Yaxin Liu9Lingjun Shen10Yanting Liu11Kai Xu12Laboratory of Infectious Diseases and Vaccine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaCancer Research Institute, Cancer Hospital, The First Affiliated Hospital of Xinxiang Medical University, Weihui, ChinaCancer Research Institute, Cancer Hospital, The First Affiliated Hospital of Xinxiang Medical University, Weihui, ChinaCancer Research Institute, Cancer Hospital, The First Affiliated Hospital of Xinxiang Medical University, Weihui, ChinaCancer Research Institute, Cancer Hospital, The First Affiliated Hospital of Xinxiang Medical University, Weihui, ChinaCancer Research Institute, Cancer Hospital, The First Affiliated Hospital of Xinxiang Medical University, Weihui, ChinaWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, ChinaCancer Research Institute, Cancer Hospital, The First Affiliated Hospital of Xinxiang Medical University, Weihui, ChinaCancer Research Institute, Cancer Hospital, The First Affiliated Hospital of Xinxiang Medical University, Weihui, ChinaIntroductionGrade II/III gliomas are invasive brain tumors with a high risk of malignant progression and significant clinical heterogeneity, highlighting the urgent need for reliable prognostic biomarkers to guide personalized treatment strategies. This study aimed to investigate the molecular mechanisms driving glioma progression and to identify potential therapeutic targets.MethodsWe analyzed 200 mitochondrial oxidative phosphorylation (OXPHOS)-related genes in 512 grade II/III glioma samples from The Cancer Genome Atlas (TCGA). Consensus clustering identified two distinct molecular subtypes (C1 and C2). Differentially expressed genes (DEGs) between subtypes were determined using the limma package. The immune cell composition and tumor microenvironment (TME) characteristics were assessed using ESTIMATE, MCPcounter, and CIBERSORT algorithms. Based on prognostic DEGs, we constructed a four-gene prognostic signature (MAOB, IGFBP2, SERPINA1, and LGR6).ResultsThe C2 molecular subtype was associated with poorer prognosis, higher immune scores, and enrichment in tumor-promoting pathways. The four-gene signature demonstrated strong prognostic performance and robustness across multiple independent validation cohorts. Immunohistochemical (IHC) analysis of clinical glioma specimens confirmed elevated protein expression levels of the four genes in tumor tissues.DiscussionOur OXPHOS-associated gene signature provides novel insights into the molecular classification, immune landscape, and prognosis of grade II/III gliomas. These findings lay the foundation for precision oncology and the development of targeted therapeutic interventions.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1638824/fullgrade II/III gliomasmitochondrial oxidative phosphorylationprognostic gene signatureRiskScore modelimmune microenvironment |
| spellingShingle | Jun Mou Min Zhang Fumin Qin Yajie Cui Keyou Xu Baoye Pang Xinyue Li Wanyi Tan Aiqi Yang Yaxin Liu Lingjun Shen Yanting Liu Kai Xu A multi-cohort validated OXPHOS signature predicts survival and immune profiles in grade II/III glioma patients Frontiers in Immunology grade II/III gliomas mitochondrial oxidative phosphorylation prognostic gene signature RiskScore model immune microenvironment |
| title | A multi-cohort validated OXPHOS signature predicts survival and immune profiles in grade II/III glioma patients |
| title_full | A multi-cohort validated OXPHOS signature predicts survival and immune profiles in grade II/III glioma patients |
| title_fullStr | A multi-cohort validated OXPHOS signature predicts survival and immune profiles in grade II/III glioma patients |
| title_full_unstemmed | A multi-cohort validated OXPHOS signature predicts survival and immune profiles in grade II/III glioma patients |
| title_short | A multi-cohort validated OXPHOS signature predicts survival and immune profiles in grade II/III glioma patients |
| title_sort | multi cohort validated oxphos signature predicts survival and immune profiles in grade ii iii glioma patients |
| topic | grade II/III gliomas mitochondrial oxidative phosphorylation prognostic gene signature RiskScore model immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1638824/full |
| work_keys_str_mv | AT junmou amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT minzhang amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT fuminqin amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT yajiecui amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT keyouxu amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT baoyepang amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT xinyueli amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT wanyitan amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT aiqiyang amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT yaxinliu amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT lingjunshen amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT yantingliu amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT kaixu amulticohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT junmou multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT minzhang multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT fuminqin multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT yajiecui multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT keyouxu multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT baoyepang multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT xinyueli multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT wanyitan multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT aiqiyang multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT yaxinliu multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT lingjunshen multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT yantingliu multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients AT kaixu multicohortvalidatedoxphossignaturepredictssurvivalandimmuneprofilesingradeiiiiigliomapatients |