Upregulation of microfibrillar‑associated protein 2 is closely associated with tumor angiogenesis and poor prognosis in hepatocellular carcinoma

Abstract

Abnormal expression of microfibrillar-associated protein 2 (MFAP2), a key regulator of cellular differentiation, affects the occurrence and progression of tumors. However, the underlying role of MAFP2 in hepatocellular carcinoma (HCC) remains unclear. In the present study, patterns of MFAP2 expression in HCC were analyzed using sequencing data from The Cancer Genome Atlas database. Expression profiles of MFAP2, as well as those of epithelial-mesenchymal transition (EMT)-related proteins, were compared between HCC pathological sections and fresh tissues. Thereafter, associations between patterns of MFAP2 expression and the clinicopathological characteristics of patients, and identified risk factors associated with disease-free survival (DFS) and overall survival (OS), were determined. The functions of MFAP2 in the EMT-induced proliferation and migration of MHCC97H cells were investigated using in vitro experiments, and the effects of MFAP2 on vascular endothelial growth factor A (VEGFA)-induced tumor angiogenesis were also investigated. Upregulation of MFAP2 expression was observed in HCC, and was often accompanied by the abnormal expression of EMT-related marker proteins. In addition, analysis of clinical data from 94 patients with tumor tissues revealed a significant positive correlation between MFAP2 expression and low DFS and low OS following surgery. Through in vitro experimentation, silencing MFAP2 expression was shown inhibit EMT, which thereby inhibited cellular proliferation and migration. Moreover, downregulation of MFAP2 inhibited tumor angiogenesis via the inhibition of VEGFA. Taken together, these findings indicate that MFAP2 has the potential to predict the prognosis of patients with HCC. MFAP2 also induces tumor cell proliferation and migration through EMT, and promotes tumor blood vessel formation through VEGFA, suggesting that MFAP2 may be a potential therapeutic target for HCC.

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

“…Next, we explored MFAP2 expression in various types of glioma and observed that MFAP2 expression levels correlated positively with tumor grade, histology, recurrence, and other biomarkers such as 1p19q codeletion, IDH status, TERT expression, ATRX status, and chromosomes 7 and 10. These outcomes correspond with a former report that MFAP2 promotes epithelial-mesenchymal transformation, proliferation, and migration in tumor cells ( Chen et al, 2020 ; Yao et al, 2020 ; Zhang et al, 2021 ). The results of the functional analysis of MFAP2 protein in glioma revealed that MFAP2 correlated with signaling pathways activated in gliomas, such as activation of matrix metalloproteinases, MET promotion of cell motility, chemokine receptor binding to chemokines and cell cycle checkpoints.…”

“…MFAP2 was recently reported to be associated with various malignant tumors. For example, as a prognostic marker of hepatocellular carcinoma, MFAP2 leads to hepatocellular carcinoma cell epithelial-mesenchymal transition, and also promotes hepatocellular carcinoma angiogenesis via vascular endothelial growth factor A ( Zhang et al, 2021 ); MFAP2, an oncogene in gastric cancer, promotes the progression of cancer through the integrin α5β1/FAK/ERK1/2 signaling pathway ( Yao et al, 2020 ); MFAP2 is highly expressed in melanoma and leads to melanoma invasion and migration by upregulating EMT-related proteins and Wnt/β-catenin signal pathway ( Chen et al, 2020 ). However, the expression and effection of MFAP2 on gliomas have yet to be reported.…”

MFAP2 contributes to the proliferation and motility of lung cancer cells via Wnt/β-catenin pathway

“…The results showed that MFAP2 plays an important role in lung cancer, consistent with the results of previous studies [9,12,15]. MFAP2 has been correlated with angiogenesis and prognosis in HCC [16]. In addition, MFAP2 is a diagnostic and prognostic biomarker of papillary thyroid cancer (PTC) [9] and can potentiate the motility of melanomas [12].…”

The role of microfibrillar‐associated protein 2 in cancer

“…For example, hepatocellular carcinoma cell migration and invasion ability were reduced by inhibiting EMTrelated protein expression in MHCC97H cells after MFAP2knockdown. Furthermore, MFAP2 inhibition by si-MFAP2 in YY-8103 and HuH-7 cells showed time-dependent low relative mobility (20,21). In vitro colorectal adenocarcinoma studies found that MFAP2 silencing inhibited the migration of SW480 and HCT116 cells (19).…”