2. Academic Validation
  3. Novel mutations of SRPX facilitate the stemness and malignant progression of glioma

Novel mutations of SRPX facilitate the stemness and malignant progression of glioma

  • Br J Cancer. 2025 Jul 15. doi: 10.1038/s41416-025-03091-5.
Siyuan Tang 1 2 3,  Chunhui Qu 1 2,  Mingyu Zhang 4,  Peijun Zhou 1 2,  Xingzhi Peng 1 2,  Zhuan Zhou 1 2,  Liangfang Shen 5,  Lifang Yang 6 7
Affiliations

Affiliations

  • 1 Department of Oncology, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
  • 2 Cancer Research Institute, School of Basic Medicine Science, Central South University, Changsha, China.
  • 3 Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China.
  • 4 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
  • 5 Department of Oncology, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. lfshen2008@163.com.
  • 6 Department of Oncology, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. yanglifang@csu.edu.cn.
  • 7 Cancer Research Institute, School of Basic Medicine Science, Central South University, Changsha, China. yanglifang@csu.edu.cn.
PMID: 40665012 DOI: 10.1038/s41416-025-03091-5
Abstract

Background: Explorations of genomic profiles are of great clinical significance for glioma due to the high tumor heterogeneity and stemness. High-depth Sequencing enabled to identify driver genes and potential treatment targets in glioma.

Methods: A whole exome Sequencing analysis of 27 Chinese patients was conducted and somatic mutation signatures were analyzed using validated computational methods. The biological roles of SRPX mutations and subsequent regulatory mechanisms were revealed by common experimental methods.

Results: We intriguingly found that SRPX drove glioma progression with two frequent in-frame deletion mutations of p.L14DEL and p.L23DEL. Mechanistically, both the two mutations of SRPX promoted binding with transcription factor AHR on its promoter, upregulated gene transcription of itself, then activated EGFR/ Akt/ Nestin pathway and contributed to aggressive tumor phenotypes and animal tumor growth. Further, knockdown of AHR or application of Akt Inhibitor suppressed the oncogenic role of mutated SRPX.

Conclusions: Our study highlighted the landscape of glioma in revealing a non-distinctive mutation and signaling pathway profile between low and high grades. More importantly, we identified a novel role of SRPX mutations in acceleration to stemness and malignant progression, which could provide new targets in improving outcomes of glioma.

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