Dataset Information

High expression of cluster of differentiation 276 indicates poor prognosis in glioma.

ABSTRACT:

Background

Glioma is the central nervous system tumor with the highest incidence rate and the molecular detection of gliomas has been the focus of research. This study aimed to investigate the guiding effect of cluster of differentiation 276 (CD276) expression on the clinical prognosis of glioma.

Methods

The TCGA and CGGA databases were used to study whether CD 276 can be used as an independent prognostic factor for gliomas. Immunohistochemistry was used to detect the expression of CD276, isocitrate dehydrogenase-1 (IDH1), matrix metallopeptidase 9 (MMP9), p53, and Ki-67, and 1p/19q co-deletion was detected by fluorescence in situ hybridization (FISH). The effects of CD276 RNA interference (RNAi) on cell invasion, cell cycle and the expression of β-catenin, tumor necrosis factor receptor 1 (TNFR1), and MMP9 were observed. Furthermore, the biological effects of CD276 gene knockout on intracranial transplanted tumors in nude mice were studied.

Results

CD276 expression was positively correlated with the extracellular matrix, collagen decomposition, and cell adhesion molecules. Immunohistochemistry and FISH showed that CD276 expression positively correlated with the glioma grade, p53 mutation, Ki-67 proliferation, and MMP9 expression; however, it negatively correlated with IDH1 mutation, 1p/19q co-deletion, and the survival rate. CD276 RNAi in U87 cells inhibited cell proliferation, migration, and invasion, but had no effect on the cell cycle. CD276 inhibited the expression of β-catenin, TNFR1, and MMP9 in U87 cells at the mRNA and protein levels. In vivo experiments showed that the tumor formation and invasion of the CD276 small interfering RNA glioma cell line in nude mice were reduced and the survival time was prolonged.

Conclusions

The present study demonstrated that high expression of CD276 in gliomas indicates a poor prognosis.

SUBMITTER: Li L

PROVIDER: S-EPMC8299877 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose: Glioma is the most common malignant brain tumor. The molecular mechanisms underlying its malignancy are not fully understood. LAMC1, which encodes extracellular matrix protein laminin ?1, has been implicated in some malignant tumors but has not been systematically evaluated in glioma. The aim of this study was to evaluate the expression of LAMC1 and its clinical significance. Patients and methods: LAMC1 protein expression in 52 fresh-frozen specimens of different pathological grade gliomas and 5 normal brain tissues was detected by Western blotting. Immunohistochemistry was used to detect LAMC1 protein expression in another set of 76 glioma tissues and 8 normal brain tissues. The associations between clinicopathological factors and LAMC1 expression were analyzed. A log-rank test and a multivariate Cox proportional hazards model were used to determine the relationship between LAMC1 expression and patient prognosis. The expression of LAMC1 at the mRNA level was analyzed in the TCGA database. Results: LAMC1 was highly expressed in high-grade glioma tissues, with moderate expression in low-grade gliomas, and weak or no expression in normal brain tissues, as detected by Western blotting and immunohistochemistry. A chi-square test indicated that LAMC1 expression was associated with pathological grade but not with other clinicopathological factors, such as age, sex, and tumor size. LAMC1 expression at the mRNA level was upregulated in high-grade gliomas compared with low-grade gliomas and normal brain tissue in the TCGA database. The Kaplan-Meier plot and log-rank test in our patient series showed that high LAMC1 expression was significantly associated with shorter survival, which was consistent with the TCGA database analysis. A multivariate Cox proportional hazards model revealed that LAMC1 expression, WHO grade, and surgery procedure were significantly correlated with overall survival and progression-free survival. Conclusion: These results demonstrated that LAMC1 may play an important role in glioma progression and may be used in the diagnosis, prognosis, and targeted therapy of glioma patients.