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

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.