ASPHD1 Is a tumor-suppressive and prognostic marker in glioma

Our plain-English summary of ASPHD1 Is a tumor-suppressive and prognostic marker in glioma, by J. Yang, F. Gao, X. Wang, et al (Frontiers in Oncology, 2025).

The study

• Authors: J. Yang, F. Gao, X. Wang, Y. Zhang, S. Li
• Journal: Frontiers in Oncology
• Published: 2025;15:1694116
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Glioma is a highly aggressive primary brain tumor. To identify novel prognostic biomolecules and potential therapeutic targets, we investigated Aspartate betahydroxylase domain-containing protein 1 (ASPHD1), encoded by the ASPHD1 gene and predicted to function as a Fe (II)/2-oxoglutarate-dependent dioxygenase involved in peptide amino-acid modification. ASPHD1 has not previously been characterized in glioma.

Methods: We assessed its expression and prognostic value using transcriptomic data from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Chinese Glioma Genome Atlas (CGGA). Co-expressed gene enrichment and DNA-methylation analyses were performed, and associations between ASPHD1 expression and overall survival (OS) were evaluated. Gene Ontology and KEGG analyses of ASPHD1 coexpressed genes indicated enrichment in synaptic signaling, ion-channel activity, and calcium-signaling pathways, suggesting a link with neuronal and synaptic function.

Results: ASPHD1 expression showed a pronounced inverse correlation with WHO grade, and higher ASPHD1 expression was associated with prolonged OS; multivariable Cox models identified low ASPHD1 as an independent adverse prognostic factor. Pan-cancer analysis further revealed that higher ASPHD1 expression was associated with longer OS in skin cutaneous melanoma (SKCM), uveal melanoma (UVM), and mesothelioma (MESO). In glioma cell lines, ASPHD1 overexpression suppressed proliferation, migration, and invasion in vitro, and inhibited tumor growth in a subcutaneous U87 xenograft model. ASPHD1 overexpression also upregulated neuronal differentiation-related genes, produced more negative resting membrane potentials on whole-cell patch-clamp recordings, enhanced depolarization-evoked Ca2+ transients on calcium imaging, and increased NeuN protein expression.

Discussion: Together, these findings identify ASPHD1 as a favorable prognostic biomarker in glioma and suggest that high ASPHD1 expression restrains glioma progression while promoting neuron-like differentiation of glioma cells.

Copyright © 2026 Yang, Gao, Wang, Zhang and Li.

In plain English

This laboratory and public-database study examined a gene, ASPHD1, in glioma, a brain tumor. It did not study asbestos. The authors analyzed gene-expression data from TCGA (674 glioma and 5 normal samples), two CGGA cohorts (325 and 693 glioma samples) and a GEO dataset. ASPHD1 levels were lower in glioma than in normal tissue and fell as tumor grade rose. Patients with above-median ASPHD1 lived longer overall than those below the median, and the authors reported low ASPHD1 as an independent risk factor in multivariable models. Of 30 cancer types checked with online tools, higher ASPHD1 was associated with longer survival in several, including mesothelioma (shown as a survival plot, without numbers in the text), and with shorter survival in one abbreviated COAD. In glioma cell lines, adding extra ASPHD1 reduced cell growth and invasion. In mice (5 control, 4 ASPHD1), U87 tumors grown under the skin were smaller, though the authors cautioned this model does not reproduce the brain environment. The authors concluded ASPHD1 appears to be a favorable prognostic marker in glioma, modest alone and needing further validation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of public gene-expression databases combined with cell-line experiments and a mouse xenograft experiment
• Who was studied: Glioma samples from public databases: TCGA (674 glioma, 5 normal), CGGA325 (325 glioma, 20 normal), CGGA693 (693 glioma, no normal) and GEO GSE7696. Also U87 and U251 human glioblastoma cell lines, and female BALB/c-nu mice (5 vector and 4 ASPHD1 mice analyzed).
• Exposure: No asbestos or fiber exposure was studied. The factor examined was ASPHD1 gene expression, split at the median into high and low groups. In the experiments, the authors increased (overexpression) or reduced (knockdown) ASPHD1 in cells.
• Main results:
  • ASPHD1 mRNA was lower in glioma than in normal tissue and decreased with increasing glioma grade (P < 0.05).
  • In TCGA glioma patients (high n = 335, low n = 335), those with high ASPHD1 had significantly longer overall survival than those with low ASPHD1 (P < 0.001).
  • In the TCGA multivariate analysis (n = 209), the authors reported low ASPHD1 expression as an independent risk factor, with hazard ratio 0.999 (95% CI 0.997 to 1.000, P < 0.05).
  • In the CGGA325 multivariate analysis (n = 294), low ASPHD1 expression had hazard ratio 0.989 (95% CI 0.978 to 0.999, P < 0.05).
  • In the pan-cancer analysis, higher ASPHD1 was associated with longer overall survival in SKCM, UVM, MESO (mesothelioma) and LGG. These results are shown as survival plots (Figure 5), and the text gives no numerical effect estimates for them.
  • In the pan-cancer analysis, higher ASPHD1 was linked to shorter overall survival in COAD.
  • In U87 cells, ASPHD1 overexpression reduced the share of proliferating cells from about 17.31% (vector control) to 13.21% (P < 0.01).
  • ASPHD1 overexpression inhibited invasion in both U87 and U251 cells.
  • In mice with U87 tumors grown under the skin (5 vector, 4 ASPHD1 overexpression), tumor volume and weight were significantly lower in the ASPHD1 group.
• The authors' conclusion: The authors concluded that ASPHD1 appears to be a favorable prognostic biomarker in glioma and may have diagnostic value, but that its performance on its own is modest and needs further validation.
• Limitations the authors state:
  • The database analyses were retrospective and used public cohorts whose patients were managed in different ways.
  • The basic biological functions of ASPHD1 remain incompletely understood.
  • The precise molecular mechanisms and signaling pathways downstream of ASPHD1 were not identified.
  • The mouse tumors were grown under the skin rather than in the brain, so the model does not fully reflect the brain environment.

Topics

Medical terms in this study, explained in our Lexicon: Overall Survival, Mesothelioma, Biomarker.

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