The role of microfibrillar‐associated protein 2 in cancer

Xu, Wanzhen; Wang, Manfeng; Bai, Yang; Chen, Yong; Ma, Xiaoshan; Yang, Zhiqing; Zhao, Lei; Li, Yunqian

doi:10.3389/fonc.2022.1002036

Cited by 6 publications

(4 citation statements)

References 96 publications

(130 reference statements)

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“…MFAP2 plays a vital role as a constituent of extracellular elastic microfibers, interacting with and influencing fibrin. Additionally, it serves as the foundational protein for the majority of Am J Transl Res 2024;16(4):1322-1336 vertebrate microfibrils [26][27][28][29][30]. Notably, MFAP2 exhibits a distinctive capability to interact with TGF-β family growth factors, Notch, Notch ligands, and various elastins [31].…”

Section: Discussionmentioning

confidence: 99%

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

2024

Am J Transl Res

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Objectives: Triple-negative breast cancer (TNBC) is characterized by significant heterogeneity, presenting a formidable challenge with a poor prognosis and a deficiency of efficacious treatment options. Methods: In this comprehensive study, we investigated the multifaceted role of Microfibril-associated glycoprotein 2 (MFAP2) in TNBC using a combination of bioinformatics analysis involving Gene Expression Omnibus (GEO), OncoDB, UALCAN, Human Protein Atlas (HPA), TIMER, STRING, DAVID, and GSCA databases and in vitro experiments, such as cell culture, MFAP2 gene knockdown, RT-qPCR, western Blot, colony formation, Cell counting kit-8, and wound healing assays. Results: Our findings demonstrated a significant up-regulation of MFAP2 mRNA in TNBC cell lines, emphasizing its potential as a diagnostic biomarker. Validation across multiple datasets further affirmed the elevated expression of MFAP2 in TNBC tissues, underscoring its prognostic relevance. Notably, our study revealed a correlation between MFAP2 expression and immune cell infiltration, suggesting its role in shaping the tumor microenvironment. STRING analysis unveiled interactions with proteins involved in elastic fibers and extracellular matrix constituents. Furthermore, KEGG pathway analysis highlighted enrichment in the TGF-beta signaling pathway, implicating MFAP2 in key cancer-related processes. Drug sensitivity analysis identified potential therapeutic targets, supporting MFAP2's utility in personalized treatment strategies. In vitro experiments corroborated the oncogenic impact of MFAP2, demonstrating its influence on TNBC cell proliferation and migration. Conclusion: These comprehensive findings position MFAP2 as a promising biomarker and therapeutic target in TNBC, offering valuable insight for future research and clinical application.

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Section: Discussionmentioning

confidence: 99%

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

2024

Am J Transl Res

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“…And TP53 mutation also may occur in BC progression. Besides, MFAP2 is an important component of ECM [ 38 ], we made the hypothesis that MFAP2 may be engaged in breast cancer tumorigenesis through affecting the stability of TP53 mutation. Moreover, TP53, transcription factor, can regulate the expression of various proteins to establish a pro-oncogenic tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

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

Huang,

Xu,

et al. 2024

Discov Onc

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Backgrounds Microfibril-associated protein 2 (MFAP2) is a protein presenting in the extracellular matrix that governs the activity of microfibrils through its interaction with fibrillin. While the involvement of MFAP2 in metabolic disorders has been documented, its expression and prognostic significance in triple-negative breast cancer (TNBC) remain unexplored. Methods We acquired datasets pertaining to breast cancer (BC) from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Next, a Venn diagram was used to identify the differentially expressed genes (DEGs). The DEGs were used to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI), immune and survival analysis. The expressions of MFAP2, PD-1 and PD-L1 were examined by immunohistochemistry and western blot and their relationship with clinical pathological parameters were analyzed by clinical specimen samples from patients with TNBC. Tumor Immune Estimation Resource (TIMER, https://cistrome.shinyapps.io/timer/) was adopted to calculate the immune infiltration level of TNBC. The link between gene expression and tumor mutational burden (TMB) was described using Spearman’s correlation analysis. Results We identified 66 differentially expressed genes (DEGs) that were up-regulated. Among these DEGs, MFAP2 was found to be overexpressed in TNBC and was associated with a lower probability of survival. This finding was confirmed through the use of immunohistochemistry and western blot techniques. Additionally, MFAP2 was found to be related to various pathological parameters in TNBC patients. Mechanistically, gene set enrichment analysis (GSEA) revealed that MFAP2 primarily influenced cellular biological behavior in terms of epithelial mesenchymal transition, glycolysis, and apical junction. Notably, MFAP2 expression was positively correlated with the abundance of macrophages, while a negative correlation was observed with the abundance of B cells, CD4 + T cells, CD8 + T cells, neutrophils and dendritic cells through immune analysis. Furthermore, it was observed that MFAP2 displayed a negative correlation not only with tumor mutational burden (TMB), a recognized biomarker for PD-1/PD-L1 immunotherapy, but also with PD-L1 in samples of TNBC. Conclusion MFAP2 may be an important prognostic biomarker for TNBC, as well as a viable target for immunotherapy in this disease.

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“…It might be involved in reshaping the extracellular matrix and regulating processes such as cell growth, programmed cell death, invasion, metastasis, and angiogenesis. However, the exact mechanism of MFAP2 in these tumor-related processes remains unclear (Xu et al, 2022). Considine et al (2021) Frontiers in Molecular Biosciences frontiersin.org utilized extensive data from two genome-wide association studies to pinpoint protein biomarkers associated with ovarian cancer risk in circulating blood.…”

Section: Protein Biomarker For Tumor Size (Microscopic-macroscopic) V...mentioning

confidence: 99%

Integrating proteomics and explainable artificial intelligence: a comprehensive analysis of protein biomarkers for endometrial cancer diagnosis and prognosis

Yasar,

Yagin,

Melekoglu

et al. 2024

Front. Mol. Biosci.

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Endometrial cancer, which is the most common gynaecological cancer in women after breast, colorectal and lung cancer, can be diagnosed at an early stage. The first aim of this study is to classify age, tumor grade, myometrial invasion and tumor size, which play an important role in the diagnosis and prognosis of endometrial cancer, with machine learning methods combined with explainable artificial intelligence. 20 endometrial cancer patients proteomic data obtained from tumor biopsies taken from different regions of EC tissue were used. The data obtained were then classified according to age, tumor size, tumor grade and myometrial invasion. Then, by using three different machine learning methods, explainable artificial intelligence was applied to the model that best classifies these groups and possible protein biomarkers that can be used in endometrial prognosis were evaluated. The optimal model for age classification was XGBoost with AUC (98.8%), for tumor grade classification was XGBoost with AUC (98.6%), for myometrial invasion classification was LightGBM with AUC (95.1%), and finally for tumor size classification was XGBoost with AUC (94.8%). By combining the optimal models and the SHAP approach, possible protein biomarkers and their expressions were obtained for classification. Finally, EWRS1 protein was found to be common in three groups (age, myometrial invasion, tumor size). This article’s findings indicate that models have been developed that can accurately classify factors including age, tumor grade, and myometrial invasion all of which are critical for determining the prognosis of endometrial cancer as well as potential protein biomarkers associated with these factors. Furthermore, we were able to provide an analysis of how the quantities of the proteins suggested as biomarkers varied throughout the classes by combining the SHAP values with these ideal models.

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The role of microfibrillar‐associated protein 2 in cancer

Cited by 6 publications

References 96 publications

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

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

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

Integrating proteomics and explainable artificial intelligence: a comprehensive analysis of protein biomarkers for endometrial cancer diagnosis and prognosis

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