AUTHOR=Zhu Jinchao , Lin Qingyuan , Zheng Haiyan , Rao Yamin , Ji Tianhai 

TITLE=The pro-invasive factor COL6A2 serves as a novel prognostic marker of glioma

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.897042

DOI=10.3389/fonc.2022.897042

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Glioma is an incurable malignant lesion with poor outcome characterized by easy recurrence after surgery with or without radiotherapy and chemotherapy. Studies have shown that <italic>COL6A2</italic> is closely related to the tumorigenesis and development of a variety of tumors. However, the role of <italic>COL6A2</italic> in glioma and the relationship between <italic>COL6A2</italic> and tumor infiltrating immune cells remain unclear.</p></sec><sec><title>Methods</title><p>Western blot, real-time <italic>PCR</italic>, a tissue microarray and immunohistochemistry were applied to detect <italic>COL6A2 mRNA</italic> and protein amounts in glioma, and all experiments were repeated three times. A tissue microarray of glioma samples was used for prognostic analysis. Detection of <italic>COL6A2</italic> co-expression with immune genes using immunohistochemical methods, and tumor modeling using nude mice for prevention and treatment studies. Based on the mRNA expression of <italic>COL6A2</italic>, patients with glioma in <italic>TCGA</italic> were divided into the low and high <italic>COL6A2</italic> expression groups, and <italic>GO</italic> and <italic>KEGG</italic> pathway analyses were performed. A <italic>PPI</italic> network was constructed using STRING, and the associations of <italic>COL6A2</italic> with tumor-infiltrating immune cells and immune genes were analyzed in the <italic>CIBERSORT</italic> and <italic>TISIDB</italic> databases. <italic>COL6A2</italic> mRNA and protein amounts were increased in glioma.</p></sec><sec><title>Results</title><p>Multiple-database and tissue microarray analyses showed that <italic>COL6A2</italic> expression in glioma was associated with poor prognosis, Tissue microarray showed that <italic>COL6A2</italic> was the highest expressed in <italic>WHO</italic> IV and significantly higher in <italic>TCGA-GBM</italic> than in <italic>TCGA-LGG</italic>. Immunohistochemistry can well demonstrate the co-expression of COL6A2 with immune genes in a tumor model established in nude mice, showing that interference with <italic>COL6A2</italic> expression may have an inhibitory effect on tumors. The mRNA expression of <italic>COL6A2</italic> was involved in 22 <italic>KEGG</italic> pathways, and <italic>GSEA</italic> analysis showed that 28 and 57 gene sets were significantly enriched at nominal p values &lt;0.01 and &lt;0.05, respectively, protein network revealed a tight interaction between <italic>COL6A2</italic> and <italic>SPARC.</italic> The <italic>CIBERSORT</italic> database indicated that <italic>COL6A2</italic> was correlated with 15 types of tumor-infiltrating immune cells, including M2 macrophages, CD8 T cells, neutrophils, gamma delta T cells, activated CD4 memory T cells, follicular helper T cells, M0 macrophages, M1 macrophages, regulatory T cells (Tregs), activated NK cells, eosinophils, activated mast cells, monocytes, activated dendritic cells, and resting CD4 memory T cells. The <italic>TISIDB</italic> database indicated that <italic>COL6A2</italic> was significantly correlated with lymphocytes such as regulatory T cell, Type 17 T helper cell, Type 1 T helper cell, and immunomodulatory genes. In addition, <italic>COL6A2</italic>-related immune regulatory genes show that most immune regulatorygenes have prognostic value for glioma, and high-risk immune genes are notconducive to the survival of glioma patients.</p></sec><sec><title>Conclusions</title><p><italic>COL6A2</italic>-related immune regulatory genes show that most immune regulatory genes have prognostic value for glioma, and high-risk immune genes are not conducive to the survival of glioma patients. <italic>COL6A2</italic> may be a novel potential prognostic biomarker of glioma and associated with tumor-infiltrating immune cells in the tumor microenvironment, and interference with <italic>COL6A2</italic> expression can inhibit tumor growth, which suggests <italic>COL6A2</italic> as a potential target for future treatment.</p></sec>