4.6 Article

KDELR1 Is an Independent Prognostic Predictor and Correlates With Immunity in Glioma

Journal

FRONTIERS IN ONCOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.783721

Keywords

KDELR1; biomarker; immunity; prognosis; glioma

Categories

Funding

  1. Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]
  2. ZJLab
  3. Shanghai Rising-Star Program [18QA1400900]
  4. Shanghai Hospital Development Center [SHDC2020CR3073B]

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This study investigates the biological function and clinical value of a new biomarker in glioma. The results suggest that KDELR1 is upregulated in glioma patients and is significantly correlated with age, pathology, and other factors. Further analysis shows that KDELR1 overexpression is associated with shorter overall survival and disease-free survival times, and acts as an independent prognostic factor for overall survival in glioma patients. Additionally, KDELR1 expression is positively associated with immune infiltration and microenvironment parameters. Immunohistochemistry confirms the correlation between KDELR1 expression and tumor grade and prognosis.
BackgroundGliomas are the most malignant central nervous system tumors. With the development of sequencing technology, more potential biomarkers related to the treatment, prognosis, and molecular classification of glioma have been identified. Here, we intend to investigate the potential biological function and clinical value of a new biomarker in glioma. MethodsKDELR1 expression data and the corresponding clinical information were downloaded from public databases and then preprocessed using R language. Correlation, Kaplan-Meier survival, and Cox regression analyses were performed to explore the clinical significance of KDELR1 in glioma patients. Furthermore, the immune infiltration and microenvironment parameters were evaluated via TIMER and CIBERSORT. Immunohistochemistry was conducted to confirm the KDELR1 expression and its correlation with immunity infiltration and prognosis. ResultsKDELR1 was upregulated in glioma samples compared with normal brain tissues, and its expression was significantly correlated with age, the World Health Organization (WHO) grade, recurrence, necrosis, microvascular proliferation, molecular classification, isocitrate dehydrogenase (IDH) mutation, and 1p/19q codeletion status. In addition, survival analysis showed that glioma patients with KDELR1 overexpression had shorter overall survival (OS) and disease-free survival times, and Cox regression analysis revealed that KDELR1 acted as an independent prognostic factor of OS in glioma patients. Gene set enrichment analysis indicated a significant enrichment of metabolism-associated pathways. KDELR1 expression was positively associated with immune infiltration (including infiltration by CD8+ T cells, CD4+ T cells, macrophages, and so on) and microenvironment parameters (including stromal, immune, and ESTIMATE scores) in gliomas. The expression of KDELR1 and its correlation with the tumor grade and prognosis were confirmed by immunohistochemistry in clinical samples (n = 119, P < 0.05). ConclusionsTaken together, these findings suggest that KDELR1 is correlated with the tumor grade, molecular classifications, and immune infiltration; highlighting that KDELR1 is a novel and promising biomarker for molecular classification, treatment, and prognostic assessment may further indicate the treating effect of immune therapy.

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