Abstract
BackgroundGlioma is the most common primary brain tumor and represents one of the most aggressive and lethal types of human cancer. BCL7 family has been found in several cancer types and could be involved in tumor progression. While the role of BCL7 family in human glioma has remained to be elucidated.MethodsParaffin-embedded tumor samples were obtained to detect BCL7 expression by performing in glioma. Data (including normalized gene expression and corresponding clinical data) were obtained from Gliovis, CGGA, GEO, cBioportal and Oncomine and were used to investigate BCL7 genes expression in glioma. Survival analyses were calculated by Kaplan–Meier methods and Cox regression analysis in TCGA and CGGA. Gene Set Enrichment Analyses (GSEA) and gene ontology (GO) analysis was employed to perform the biological processes enrichment.ResultsBCL7A expression in glioma tissues was lower compared to non-tumor brain tissues (NBT), and exhibited a negative correlation with glioma grades. Results from immunohistochemical (IHC) staining and public dataset validation demonstrated that BCL7B and BCL7C were highly expressed in glioma tissues compared to NBT. Cox regression analysis identified BCL7A as the only gene in the BCL7 family that was independently associated with the prognosis of lower-grade glioma (LGG) and glioblastoma (GBM). GO and GSEA analyses revealed the potential contribution of BCL7A in adaptive immune response and neutrophil activation in the tumor microenvironment. Moreover, we found that BCL7A had no prognostic effect on the overall survival of GBM patients who received IR only; however, patients who received chemotherapy (TMZ) combined with IR in the high BCL7A group survived longer than patients in the low BCL7A group (HR = 0.346, p < 0.05).ConclusionBCL7A is a new tumor suppressor gene and can be adopted as a biomarker for independent prognosis in glioma and to evaluate response to TMZ.
Highlights
Gliomas account for nearly 80% of primary malignant brain tumors [1]
Transcriptional level of B-cell leukemia protein 7 (BCL7) in glioma To acquire more comprehensive information on the expression of the BCL7s family, we employed the cBioportal, Oncomine, Gliovis, and Gene Expression Omnibus (GEO) datasets to assess for gene expression for BCL7s family in glioma
BCL7A mRNA expression was significantly low in glioma tissues compared to normal brain tissues (NBTs) in 7 out of the 8 datasets, except for the Gravendeel dataset (Fig. 1B)
Summary
Gliomas account for nearly 80% of primary malignant brain tumors [1]. According to the World Health Organization (WHO) classification, gliomas occur in four grades. Liu et al J Transl Med (2021) 19:335 predicting tumor malignancy and clinical prognosis. Such molecular alterations are crucial in understanding the classification, diagnosis, and management of gliomas. This calls for urgent exploration to identify more novel molecular markers to predict prognosis and guide treatment. In B cell malignancy, BCL7A was overexpressed in late B cell differentiation It was lowly expressed in mature T cells and late plasma cells. Researchers need to explore the role of the BCL7 gene family in glioma, on their expression pattern and potentially associated genetic functions. While the role of BCL7 family in human glioma has remained to be elucidated
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