AI Article Synopsis
- Gliomas are aggressive brain tumors, and the study investigated the role of latent TGF binding proteins (LTBP), specifically LTBP2, as potential biomarkers and their impact on glioma progression and immune response.
- The analysis included 2407 glioma samples to evaluate LTBP2 expression with results showing higher levels of LTBP2 correlate with worse survival outcomes and increased immune infiltration in glioma tissues.
- Experimental results indicated that reducing LTBP2 expression slowed tumor growth and increased tumor sensitivity to treatment, suggesting that LTBP2 could be a valuable target for glioma therapies.
Article Abstract
Background: Gliomas are the highly aggressive brain tumor and also the most devastating human tumors. The latent TGF binding proteins (LTBP) had been found to be involved in malignant biological process and could be used as potent biomarkers in several solid tumors. While the role of LTBP family in human glioma remain to be elucidated.
Methods: Normalized gene expression and corresponding clinical data of 2407 gliomas samples in public datasets were downloaded from Gliovis. Kaplan-Meier methods and Cox regression analysis was used for survival analyses.Western blot (WB) and Immunohistochemical (IHC) testing were employed to test LTBPs protein level in 154 gliomas samples. Correlation between LTBP2 expression and immune infiltration was evaluated by immunofluorescence (IF) and IHC in glioma tissues. CCK8 and flow cytometric analysis were used to detect the effect of LTBP2 on glioma cells. Orthotopic glioma- mouse models were utilized to evaluate effects in vivo.
Results: LTBP2 mRNA level was dramatically higher in glioma samples compared with non-tumor brain tissues in XENA-TCGA_GTEx, Gill and Gravendeel datasets (all P < 0.01), and its expression positively correlated with glioma WHO grade, IDH1/2 wildtype and mesenchymal subtypes. These results were confirmed by In-house cohort which was detected by WB and IHC. We found that gliomas patients with high LTBP2 level had shorter OS than those with low LTBP2 level. LTBP2 expression significantly associated with glioma immune score (Spearman r = 0.68, P < 0.01)) and strongly correlated with infiltration degreee of macrophages both in lower grade gliomas (LGG) and GBM. Knocking down LTBP2 obviously reduced proliferation and enhanced sensitivity to temozolomide in U87 and U251 cells. Nude mice with lower expression of LTBP2 had slower tumor growth, and accompanied by less tumor-associated macrophages (TAMs) infiltration detected by IHC staining in vivo. Finally, low LTBP2 expression glioma patients who received chemotherapy survived longer than patients with high LTBP2 expression.
Conclusion: LTBP2 could be used as a prognostic marker, and high LTBP2 expression related to abundant TAMs infiltration and with a worse response to chemotherapy.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466037 | PMC |
| http://dx.doi.org/10.1186/s12885-024-12976-2 | DOI Listing |
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