image: Figure 1: LRIG1 expression negatively correlates with WHO grades of gliomas. Representative Western Blot can be seen in Figure 9. (A–E) Western blot analysis of LRIG1 protein level. LRIG1 expression is significantly higher in control tissue (A, p = 0.0004). Grade II gliomas showed a tendency towards a higher LRIG1 expression than grade III gliomas (B) and significantly higher expression than sec. GBMs (C, p = 0.0079). Grade III tended to have a higher expression of LRIG1 than secondary GBMs (D, n.s.)). Low grade gliomas had significantly higher protein levels than high grade gliomas (grade III and GBMs) (E, p = 0.0118). (F–J) PCR analysis of LRIG1 mRNA. LRIG1 expression tended to be higher in gliomas (F, n.s.). LRIG1 transcriptional level correlates with protein level. There was a significantly higher expression in grade II compared to grade III (G, p = 0.0096) and secondary GBMs (H, p < 0.0001). Grade III tended to have a higher LRIG1 expression than secondary GBMs (I, n.s.). Transcription was significantly higher in low-grade compared to high-grade gliomas (J, p < 0.0001). (Statistical significance is marked with *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001; Abbreviation: ns: not significant).
Credit: Copyright: © 2025 Happe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“Our results reinforce suggestions that LRIG1-3 could function as diagnostic markers and therapeutic targets in the treatment of gliomas.”
BUFFALO, NY – November 12, 2025 – A new research paper was published in Oncotarget (Volume 16) on November 6, 2025, titled “LRIG1-3 in gliomas: LRIG1 protein expression decreased in higher grade gliomas.”
In this study by Marlene Happe, Saskia Kuhl, Lukas Görtz, Roland Goldbrunner and Marco Timmer, from the University of Cologne, researchers found that the LRIG1 protein, which may help suppress tumors, is present at lower levels in more aggressive gliomas, a type of brain tumor. The findings suggest that LRIG1 could serve as a useful marker for tumor severity and potentially as a target for future therapies.
Gliomas are the most common malignant brain tumors in adults and carry a poor prognosis, particularly in their most severe form, glioblastoma. This study investigated three related proteins: LRIG1, LRIG2, and LRIG3, which are involved in regulating cell growth signals. While LRIG1 and LRIG3 have shown tumor-suppressing effects in previous studies, LRIG2 is thought to support tumor growth. The researchers analyzed tumor samples from patients to understand how these proteins behave across different glioma grades and how they respond to chemotherapy.
The results showed that LRIG1 protein levels decline significantly as tumor grade increases. Low-grade gliomas displayed much higher LRIG1 expression than high-grade tumors. Among high-grade tumors, primary glioblastomas had the lowest levels of LRIG1. Interestingly, secondary glioblastomas, which typically develop from lower-grade tumors, had higher levels of LRIG1 than primary glioblastomas. This difference may contribute to their relatively better clinical outcomes. These results highlight LRIG1’s potential role in slowing tumor progression.
In contrast, LRIG2 showed a more complex pattern. While its gene expression was higher in lower-grade tumors, the actual protein levels were slightly elevated in higher-grade ones, which are more aggressive. This mismatch suggests that processes occurring after gene transcription may influence how much LRIG2 protein is produced.
“However, our data on LRIG2 indicate that its role in glioma may be more complex than previously thought, warranting further investigation.”
Concerning LRIG3, it was found in higher amounts in glioma tissue compared to surrounding healthy tissue. Its expression was particularly high in low-grade tumors. However, chemotherapy did not consistently affect LRIG3 levels, and results varied depending on tumor type and treatment status.
Overall, the study suggests that members of the LRIG protein family, especially LRIG1, could serve as important biomarkers to distinguish between glioma types and grades. Although chemotherapy did not significantly change their expression in most cases, these proteins have high potential as diagnostic tools or therapeutic targets. Further research is needed to better understand their roles in glioma development and treatment response.
DOI: https://doi.org/10.18632/oncotarget.28775
Correspondence to: Marco Timmer – marco.timmer@uk-koeln.de
Abstract video: https://www.youtube.com/watch?v=ZHsKLBEyBbM
Keywords: cancer, oncology, glioma, glioblastoma, LRIG1, LRIG2, LRIG3
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Journal
Oncotarget
Method of Research
News article
Subject of Research
Not applicable
Article Title
LRIG1-3 in gliomas: LRIG1 protein expression decreased in higher grade gliomas
Article Publication Date
6-Nov-2025
COI Statement
Authors have no conflicts of interest to declare.