2. Academic Validation
  3. Thioredoxin related transmembrane protein 1acts as a prognostic indictor and promotes proliferation and TMZ resistance of lower-grade glioma

Thioredoxin related transmembrane protein 1acts as a prognostic indictor and promotes proliferation and TMZ resistance of lower-grade glioma

  • Sci Rep. 2025 Feb 12;15(1):5246. doi: 10.1038/s41598-025-89908-y.
Hongyan Hui 1 2 3,  Fang Zhou 1 2 3,  Sujuan Pei 1 2 3,  Wenyan Zhou 4,  Jie Shang 5,  Pengwei Wang 1 2 3,  Zhijian Deng 1 2 3,  Xiang Zhou 6
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan, People's Republic of China.
  • 2 Clinical Pharmacy, Henan Province Key Subjects of Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan, People's Republic of China.
  • 3 Xinxiang Key Laboratory for Individualized Drug Use Research for Immune Diseases, Weihui, 453100, Henan, People's Republic of China.
  • 4 Department of Medical Imaging, The First Affiliated Hospital of Xinxiang Medical University, 453100, Weihui, Henan, People's Republic of China.
  • 5 Medical Science, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan, People's Republic of China.
  • 6 Brain Hospital, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan, People's Republic of China. 44906700@qq.com.
PMID: 39939413 DOI: 10.1038/s41598-025-89908-y
Abstract

Thioredoxin Related Transmembrane Protein 1 (TMX1) encodes a thiol-disulfide oxidoreductase and regulates cleavage, formation, or isomerization of disulfide bonds among cysteine residues in proteins. Using bioinformatic analysis, we firstly prove TMX1 is significantly upregulated in lower-grade gliomas (LGGs) and associated with poor prognosis of LGG patients. Besides, it's also highly expressed in higher WHO grade, 1p/19q non-co-deleted and isocitrate dehydrogenase (IDH) wildtype LGGs, thus we established a TMX1-based nomogram model, which exhibits a strong and stable predictive ability in the prognosis of LGG patients. Then, we also noticed that TMX1 was significantly associated with the immune cell infiltrations in LGGs, especially in B cell, CD8+ T cell, CD4+T cell, dendritic cell, macrophage and neutrophil. Meanwhile, it was also highly correlated to the expressions of MKI67, PCNA, PROM1 and SOX2 in LGGs, and that higher TMX1 LGGs showed a stronger resistance to temozolomide (TMZ). Finally, in our in vitro and in vivo experiments, we verified that TMX1 is highly expressed in LGG patients clinically, and it not only regulates the proliferative ability of SW1088 and SW1783 cells both in vitro and in vivo, it can also be inhibited to increase the TMZ therapy sensitivity in vivo. These results revealed that TMX1 acts as a strong prognostic biomarker in LGGs, and targeting TMX1 can be an efficient way to increase the TMZ therapy in LGG patients.

Keywords

Cell proliferation; Lower grade glioma (LGG); Temozolomide resistance; Thioredoxin related transmembrane protein 1 (TMX1).

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