Integrated analysis of microfibrillar-associated proteins reveals
            <i>MFAP4</i>
            as a novel biomarker in human cancers

Yang, Jue; Song, Hui; Chen, Li; Cao, Kun; Zhang, Yongqiang; Li, Yanmei; Hao, Xiao‐Jiang

doi:10.2217/epi-2018-0080

Cited by 37 publications

(24 citation statements)

References 62 publications

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“…In the present study, CSRP1 was downregulated in ACC, which indicated that CSRP1 may be a tumor suppressor gene. MFAP4 is a tumor suppressor gene in prostate cancer and it displays low expression in breast cancer (29,30). By contrast, downregulated MFAP4 may lead to adverse clinical incidents in ovarian cancer (31).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic screening and identification of downregulated hub genes in adrenocortical carcinoma

Zhang

Miao

et al. 2020

Exp Ther Med

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The molecular mechanisms of adrenocortical carcinoma (ACC) carcinogenesis and progression remain unclear. In the present study, three microarray datasets from the Gene Expression Omnibus database were screened, which identified a total of 96 differentially expressed genes (DEGs). A protein-protein interaction network (PPI) was established for these DEGs and module analysis was performed using STRING and Cytoscape. A total of eight hub genes were identified from the most significant module; namely, calponin 1 (CNN1), myosin light chain kinase (MYLK), cysteine and glycine rich protein 1 (CSRP1), myosin heavy chain 11 (MYH11), fibulin extracellular matrix protein 2 (EFEMP2), fibulin 1 (FBLN1), microfibril associated protein 4 (MFAP4) and fibulin 5 (FBLN5). The biological functions of these hub genes were analyzed using the DAVID online tool. Changes in the expression of hub genes did not affect overall survival; however, downregulated EFEMP2 decreased disease-free survival. CSRP1 and MFAP4 expression levels were associated with adverse clinicopathological features. In conclusion, although all eight hub genes were downregulated in ACC, they appeared to have important functions in ACC carcinogenesis and progression. Identification of these genes complements the genetic expression profile of ACC and provides insight for the diagnosis, treatment and prognosis of ACC.

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Section: Discussionmentioning

confidence: 99%

Bioinformatic screening and identification of downregulated hub genes in adrenocortical carcinoma

Zhang

Miao

et al. 2020

Exp Ther Med

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“…Subsequently, copy number variant (CNV) analysis in 464 individuals identified MFAP4 as a candidate gene for the severe cardiac malformations associated with left-sided congenital heart disease (LS-CHD) 2 . More recently, numerous studies have implicated MFAP4 as a prognostic marker (or biomarker) for assorted cancers, including ovarian 3 , 4 , mammary 5 and prostate 6 , as well as hepatic and pulmonary fibrosis 7 and chronic obstructive pulmonary disease (COPD) 8 . Despite the growing list of diseases that implicate MFAP4 in their aetiology, the exact function of MFAP4 in vivo remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Microfibril-associated glycoprotein 4 (Mfap4) regulates haematopoiesis in zebrafish

Ong

Vos

Meroshini

et al. 2020

Sci Rep

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Microfibril-associated glycoprotein 4 (MFAP4) is an extracellular matrix protein belonging to the fibrinogen-related protein superfamily. MFAP4 is produced by vascular smooth muscle cells and is highly enriched in the blood vessels of the heart and lung, where it is thought to contribute to the structure and function of elastic fibers. Genetic studies in humans have implicated MFAP4 in the pathogenesis of Smith-Magenis syndrome, in which patients present with multiple congenital abnormalities and mental retardation, as well as in the severe cardiac malformation left-sided congenital heart disease. Comprehensive genetic analysis of the role of MFAP4 orthologues in model organisms during development and tissue homeostasis is however lacking. Here, we demonstrate that zebrafish mfap4 transcripts are detected embryonically, resolving to the macrophage lineage by 24 h post fertilization. mfap4 null mutant zebrafish are unexpectedly viable and fertile, without ostensible phenotypes. However, tail fin amputation assays reveal that mfap4 mutants have reduced numbers of macrophages, with a concomitant increase in neutrophilic granulocytes, although recruitment of both cell types to the site of injury was unaffected. Molecular analyses suggest that loss of Mfap4 alters the balance between myeloid and lymphoid lineages during both primitive and definitive haematopoiesis, which could significantly impact the downstream function of the immune system.

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“…Interestingly, when the Euclidean distance and the Manhattan distance were used to characterize tumor similarity, we found that the high-grade tumors were more dissimilar to each other than the low-grade tumors (Additional file 1: Table S6). Among them was PSA (KLK3), and several other well established PCa-associated proteins like AGR2 [36], MDH2 [37], MFAP4 [38] and FABP5 [39]. We observed that for some of these top 20 proteins,…”

Section: Resultsmentioning

confidence: 87%

Convergent network effects along the axis of gene expression during prostate cancer progression

Charmpi

Guo

Zhong

et al. 2020

Preprint

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36Tumor-specific genomic aberrations are routinely determined by high throughput genomic 37 measurements. However, it is unclear how complex genome alterations affect molecular networks 38 through changing protein levels, and consequently biochemical states of tumor tissues. Here, we 39 investigated how tumor heterogeneity evolves during prostate cancer progression. In this study, we 40 performed proteogenomic analyses of 105 prostate samples, consisting of both benign prostatic 41 hyperplasia regions and malignant tumors, from 39 prostate cancer (PCa) patients. Exome sequencing, 42 copy number analysis, RNA sequencing and quantitative proteomic data were integrated using a network-43 based approach and related to clinical and histopathological features. In general, the number and 44 magnitude of alterations (DNA, RNA and protein) correlated with histopathological tumor grades. 45Although common sets of proteins were affected in high-grade tumors, the extent to which these proteins 46 changed their concentrations varied considerably across tumors. Our multi-layer network integration 47 identified a sub-network consisting of nine genes whose activity positively correlated with increasingly 48 aggressive tumor phenotypes. Importantly, although the effects on individual gene members were barely 49 detectable, together the perturbation of this sub-network was predictive for recurrence-free survival time. 50The multi-omics profiling of multiple tumor sites from the same patients revealed cases of likely shared 51 clonal origins as well as the occasional co-existence of multiple clonally independent tumors in the same 52 prostate. Overall, this study revealed molecular networks with remarkably convergent alterations across 53 tumor sites and patients, but it also exposed a diversity of network effects: we could not identify a single 54 sub-network that was perturbed in all high-grade tumor regions. 55 56 57

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Integrated analysis of microfibrillar-associated proteins reveals MFAP4 as a novel biomarker in human cancers

Abstract: This integrated analysis provides new insights into MFAPs in human cancers and indicates that MFAP4 could be used as novel biomarker for developing therapies against human cancers.

Cited by 37 publications

References 62 publications

Bioinformatic screening and identification of downregulated hub genes in adrenocortical carcinoma

Bioinformatic screening and identification of downregulated hub genes in adrenocortical carcinoma

Microfibril-associated glycoprotein 4 (Mfap4) regulates haematopoiesis in zebrafish

Convergent network effects along the axis of gene expression during prostate cancer progression

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