Microfibrillar-associated protein 2 is a prognostic marker that correlates with the immune microenvironment in glioma

Abstract

Aims: microfibrillar-associated protein 2 (MFAP2), a component of the extracellular matrix, plays key roles in regulating growth factor signal transduction and various malignant tumors. However, the clinicopathological features of microfibrillar-associated protein 2 in gliomas have not been elucidated to date.Methods: TCGA and CGGA databases were used to study the expression of microfibrillar-associated protein 2 in glioma and its relationship with clinicopathological features of patients with glioma. Western blotting was performed to detect the expression of microfibrillar-associated protein 2 protein in tissue samples from glioma patients. Gene set enrichment analysis (GSEA) was applied to detect biological processes and signal pathways related to microfibrillar-associated protein 2. Single-sample gene set enrichment analysis, TIMER 2.0, and TISIDB databases were used to evaluate the role of microfibrillar-associated protein 2 in tumor immune characteristics. The prognostic role of microfibrillar-associated protein 2 in glioma was analyzed using the Kaplan-Meier method and Cox regression. Survival data were used to establish a nomogram prediction model.Results: microfibrillar-associated protein 2 expression was significantly elevated in gliomas. receiver operating characteristic analysis revealed good discrimination of microfibrillar-associated protein 2 between glioma and normal tissues. High expression of microfibrillar-associated protein 2 was associated with malignant phenotypes, such as histological type. Based on gene set enrichment analysis, we identified pathways associated with high microfibrillar-associated protein 2 expression. High microfibrillar-associated protein 2 expression was related to the infiltration of tumor immune cells, including Th2 cells and macrophages, and correlated with key markers of T-cell exhaustion. Based on the TISIDB database, microfibrillar-associated protein 2 was observed to be associated with chemokines, chemokine receptors, and multiple immunoinhibitors in glioma. Kaplan–Meier survival analyses revealed that high microfibrillar-associated protein 2 expression predicted poor overall survival, DSS, and PFS in patients with glioma. By combining microfibrillar-associated protein 2 and other prognostic factors, a nomogram prognostic prediction model was constructed, which demonstrated an ideal prediction effect.Conclusion: microfibrillar-associated protein 2 is a potential prognostic marker that plays a key role in glioma development given its association with malignant phenotypes, cancer-related pathways and tumor immunity.

The potent potential of MFAP2 in prognosis and immunotherapy of triple-negative breast cancer

“…M2 has anti-inflammatory and carcinogenic properties compared to M1, which has anti-tumor properties [ 33 ]. Our research investigated MFAP2 expression is positively correlated to macrophages in TNBC and previous study has reported the overexpression of MFAP2 is positively related to markers of Th2 cells and M2 macrophages in glioma [ 34 ], implying MFAP2 performs a crucial role in tumor immunity modulation. Because of this, MFAP2 may affect the immune infiltration of TNBC in similar ways and be a target for immunotherapy in the future.…”

The use of MFAP2 for diagnosis, prognosis and immunotherapy of triple-negative breast cancer

“…Our study revealed a significant correlation (p-value < 0.05) between MFAP2 expression and various immune cell types, including CD8+ T cells, CD4+ T cells, macrophages, and neutrophils. A prior investigation has also highlighted the positive association between MFAP2 overexpression and markers of Th2 cells and M2 macrophages in glioma [38], suggesting a pivotal role for MFAP2 in modulating tumor immu-nity. Consequently, it is plausible that MFAP2 may exert similar effects on the immune infiltration of TNBC, positioning it as atarget for future immunotherapeutic interventions.…”

The role of microfibrillar‐associated protein 2 in cancer

“…In head and neck squamous cell carcinoma, the MFAP2 marker is expressed at higher levels (at least 13 times or more) in tumors than in normal tissues, as verified using RT-qPCR ( 28 ). In glioma, Our previous research shows that MFAP2 mRNA was upregulated in tumor tissues compared with that in normal tissues through bioinformatics analysis using TCGA and CGGA databases, and western blotting analysis confirmed that MFAP2 protein expression levels in tumor tissues were significantly higher than those in the adjacent tissues ( 30 ). The above data showed that MFAP2 was upregulated in many tumor tissues, it favors specific tumor type.…”

“…As a potential biomarker of head and neck squamous cell carcinoma tumorigenesis, MFAP2 is significantly overexpressed in SAGE tumor libraries ( 28 ). In addition, MFAP2 is a prognostic marker that correlates with the immune microenvironment in glioma ( 30 ). MFAP2 is important in the prognosis of the above tumor types; however, the specific mechanism and prognostic value of MFAP2 in other cancers with low expression of MFAP2, such as Kidney chromophore, Kidney renal clear cell carcinoma, Kidney renal papillary cell carcinoma, and Prostate adenocarcinoma, need to be further explored.…”

“…In our previous research, the expression level of MFAP2 in glioma was positively correlated with Th2 cells, macrophages, eosinophils, neutrophils and T cells. Additionally, MFAP2 expression level in glioma was positively correlated with key markers of T-cell exhaustion ( 30 ). These results suggest that the high expression of MFAP2 in different types of tumors can form tumor immune infiltration, and then regulate tumor microenvironment, which plays an important role in immunotherapy of a variety of tumors, deserve further studies for their potential clinical implications.…”