Genetically predicted circulating protein biomarkers and ovarian cancer risk

Considine, Daniel; Jia, Guochong; Shu, Xiang; Schildkraut, Joellen M.; Pharoah, Paul D.P.; Wang, Zheng; Kar, Siddhartha

doi:10.1016/j.ygyno.2020.11.016

Cited by 17 publications

(24 citation statements)

References 36 publications

(34 reference statements)

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“…12 In addition, Considine et al confirmed the overlapping genetic association signals between plasma protein levels of MFAP2 and EOC risk by using the regional genome map. 13 Based on this, we evaluated MFAP2 expression using the TCGA database of ovarian cancer cohort high-throughput RNA-sequencing data Gene Expression Profiling Interactive Analysis (GEPIA; http://gepia.cancer-pku.cn).…”

Section: Introductionmentioning

confidence: 99%

MFAP2 aggravates tumor progression through activating FOXM1/β‐catenin‐mediated glycolysis in ovarian cancer

Zhao

Sun

Zhang

et al. 2022

The Kaohsiung J of Med Scie

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Ovarian cancer is one of the most common gynecological tumors that seriously endanger the health and quality of life of women. Microfibril‐associated protein 2 (MFAP2) has been demonstrated to play crucial roles in the development of multiple tumors. However, the function of MFAP2 in ovarian cancer remains unclear. In this study, we found that MFAP2 was upregulated in ovarian cancer and cells and was positively correlated with FOXM1 and glycolysis‐related genes. The results of Cell Count Kit‐8, colony formation, and flow cytometry assays indicated that MFAP2 promoted cell proliferation. In addition, MFAP2 promotes cell proliferation, glucose uptake, lactate production; increases ATP levels, extracellular acidification ratio, and oxygen consumption ratio in ovarian cancer cells and increases the expression of glycolytic proteins. Further mechanistic analysis suggests that MFAP2 promotes FOXM1/β‐catenin‐mediated glycolysis signaling in ovarian cancer cells. Knockdown of MFAP2 inhibits ovarian cancer xenograft tumor growth and expression of Ki‐67, MFAP2, FOXM1, GLUT1, HK2, and β‐catenin in mice. In conclusion, MFAP2 promotes cell proliferation and glycolysis by modulating the FOXM1/β‐catenin signaling pathway in ovarian cancer, which may offer a fresh insight into the treatment of ovarian cancer in the glycolysis pathway.

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Section: Introductionmentioning

confidence: 99%

MFAP2 aggravates tumor progression through activating FOXM1/β‐catenin‐mediated glycolysis in ovarian cancer

Zhao

Sun

Zhang

et al. 2022

The Kaohsiung J of Med Scie

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“…Previous studies have shown that the gene that codes MFAP2 is located at 1p36.13, and is associated with several malignant tumor types ( 6 , 7 ). Consequently, MFAP2 is upregulated in breast cancer ( 8 ), thyroid cancer ( 9 ), melanoma ( 10 ), ovarian cancer ( 11 ) and gastric cancer ( 12 , 13 ), and associated with the occurrence and progression of these tumors. Previous studies have also shown that MFAP2 is upregulated in HCC ( 14 ), but its role in the occurrence and development of the disease is unclear.…”

Section: Introductionmentioning

confidence: 99%

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

2021

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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.

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“…It is also the constitutive protein of most vertebrate microfibrils [ 25 ]. A representative feature of MFAP2 is its capacity to work with TGF- β family growth factors, Notch, and Notch ligands, as well as a variety of elastins [ 26 ]. Mutations of MFAP2 gene may indicate thrombosis, thoracic aneurysms, metabolic diseases, and osteopenia in humans [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…A previous study pointed out that MFAP2 is a novel microRNA-29 target, and miR-29/MFAP2/integrin α 5 β 1/FAK/ERK1/2 might be an important carcinogenic pathway in gastric cancer progression [ 10 ]. Another study has also indicated the relevance of MFAP2 in hepatic carcinoma, whereby MFAP2 overexpression in hepatic carcinoma is associated with cancer staging, poor OS, and disease-specific survival [ 9 , 26 ]. An in vitro experiment showed that downregulation of MFAP2 inhibited the proliferation and migration levels of liver cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis of Microfibrillar-Associated Protein 2 (MFAP2) Based on Bioinformatics and qPCR Verification

Qiu

Miao

Wang

et al. 2022

Journal of Oncology

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MFAP2 has been reported to play an oncogenic role in several types of human cancers. However, the expression profile of MFAP2 in various cancers and its impact on prognosis and immune infiltration remain unclear. In this study, the mRNA expression and protein expression of MFAP2 in normal tissues, tumor cell lines, and 33 malignant tumor tissues were analyzed comprehensively using Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), and The Cancer Genome Atlas (TCGA), Oncomine and UALCAN databases, and the expression of MFAP2 in different grades and stages of cancers was assessed using Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Tumor and Immune System Interaction Database (TISIDB). In general, MFAP2 showed distinct expression in most tumor and normal tissues, closely associated with higher tumor grade, higher tumor stage, and poor survival in multiple cancers. A search of the UALCAN database and the cBioPortal database revealed that this difference in mRNA level expression could be partly attributed to abnormal DNA methylation and mutations at the genomic level. In addition, MFAP2 expression was also associated with tumor mutation burden, microsatellite instability, and neoantigens in different cancer types. More importantly, the TIMER and TISIDB databases also showed that MFAP2 levels were significantly correlated with immune infiltration abundance and immune-related gene markers, as well as ESTIMATE scores. By qPCR, MFAP2 expression was validated in four kinds of tumor tissue samples. The present study combined several databases and performed a pan-cancer analysis of the expression profile, methylation, and mutation for MFAP2 and its implications for prognosis and immune infiltration, suggesting that MFAP2 could contribute to malignant properties of many tumors. MFAP2 may be an important biomarker with prognostic value and has the potential to be a target for tumor immunotherapy.

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Genetically predicted circulating protein biomarkers and ovarian cancer risk

Cited by 17 publications

References 36 publications

MFAP2 aggravates tumor progression through activating FOXM1/β‐catenin‐mediated glycolysis in ovarian cancer

MFAP2 aggravates tumor progression through activating FOXM1/β‐catenin‐mediated glycolysis in ovarian cancer

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

Pan-Cancer Analysis of Microfibrillar-Associated Protein 2 (MFAP2) Based on Bioinformatics and qPCR Verification

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