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ORIGINAL RESEARCH ARTICLE

Prognostic significance of HTR6 expression and its association with immune infiltration in low-grade glioma

Jiayu Gu1,2† ,  Zhiqiang He3† ,  Shengnan He4† ,  Jing Du5 ,  Shaofeng Jiang6 ,  Dandan Li7* ,  Wei Zhang5*
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1 Department of Pharmacy, Shenzhen People’s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong , China
2 Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Department of Geriatrics, Shenzhen People’s Hospital, Shenzhen, Guangdong , China
3 Department of Laboratory Medicine, Zigong Fourth People’s Hospital, Zigong, Sichuan , China
4 Department of Breast and Thyroid Surgery, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong , China
5 Department of Clinical Laboratory, Peking University Shenzhen Hospital, Shenzhen, Guangdong , China
6 Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi , China
7 Experimental Center, Shenzhen Pingle Orthopedic Hospital (Shenzhen Pingshan Traditional Chinese Medicine Hospital), Shenzhen, Guangdong , China
†These authors contributed equally to this work.
EJMO, 026130140 https://doi.org/10.36922/EJMO026130140
Received: 24 March 2026 | Revised: 28 August 2026 | Accepted: 11 September 2026 | Published online: 29 September 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Low-grade glioma (LGG), defined herein as WHO grade II and III diffuse gliomas including astrocytomas and oligodendrogliomas, is a clinically and molecularly heterogeneous group of primary brain tumors with variable outcomes, highlighting the need for reliable prognostic biomarkers and immune-related therapeutic targets.

Objective: The purpose of this research was to determine the prognostic significance of HTR6 in LGG and its connection to immune cell infiltration.

Methods: Multiple bioinformatics analyses were performed to characterize HTR6 expression in normal and tumor tissues and to examine its associations with clinicopathological characteristics, prognosis, and immune infiltration status.

Results: In LGG, HTR6 expression was inversely correlated with SPI1, a candidate upstream transcription factor predicted to regulate HTR6. Low HTR6 expression was closely linked to shorter overall survival and progression-free survival. Kaplan–Meier survival analysis, along with univariate and multivariate Cox regression analyses, suggested that HTR6 expression is associated with prognosis in LGG. Functional enrichment and immune infiltration analyses demonstrated that HTR6 was involved in immune-related pathways and correlated with tumor immune infiltration patterns, which was further confirmed by immune checkpoint gene correlation analysis.

Conclusion: Lower HTR6 expression was associated with poorer survival outcomes and distinct immune-infiltration patterns in LGG. However, this study is limited by its retrospective bioinformatics-only design without experimental validation, and by the use of a traditional glioma classification system that does not fully incorporate the WHO 2021 molecular criteria (e.g., isocitrate dehydrogenase status and 1p/19q codeletion). Therefore, the conclusions should be considered preliminary and warrant further verification.

Keywords
HTR6
Low-grade glioma
Immune infiltration
Prognostic biomarker
Funding
This work was supported by the following funding sources: (i) 2025 Research Fund for Supportive Care in Cancer—A Designated Program of the Guangdong Hospital Pharmacy Research Fund (Fuxing Fund, No. 2025A02009); (ii) 2025 Special Research Project of National Health Commission Capacity Building and Continuing Education Center (No. GWJJZX20251007039); (iii) Open Funds of the Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation (Nos. 2023KF011 and 2024KF012); and (iv) Shenzhen Science and Technology Basic Research Project (No. JCYJ20250604183724032).
Conflict of interest
The authors declare no conflict of interest.
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