Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival

Xu, Yinghui; Wang, Yanru; Liu, Hongliang; Shi, Qiong; Zhu, Dakai; Amos, Christopher I.; Fang, Shenying; Lee, Jeffrey E.; Hyslop, Terry; Li, Xin; Han, Jiali; Wei, Qingyi

doi:10.1002/mc.22716

Cited by 6 publications

(5 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some studies have indicated that high expression of MMP16 is associated with the proliferation, migration, and invasion of cutaneous squamous cell carcinoma cells [ 51 ], while knockdown of MMP16 could inhibit cell proliferation and invasion in chordoma cells [ 11 ]. Moreover, some variations in MMP16 have been found to be associated with different types of diseases [ 52 , 53 ]. In our study, MMP16 was found to be upregulated in UVM, and high expression was associated with shorter OS and DFS.…”

Section: Discussionmentioning

confidence: 99%

MMP1 and MMP9 are potential prognostic biomarkers and targets for uveal melanoma

et al. 2021

View full text Add to dashboard Cite

Background Uveal melanoma (UVM) is the leading cause of eye-related mortality worldwide. This study aimed to explore the expression and prognostic value of matrix metalloproteinases (MMPs) in UVM. Methods Gene expression levels were obtained from the Gene Expression Omnibus (GEO) and Oncomine databases. Functional and pathway enrichment analyses were performed using the Metascape database. GeneMANIA was then applied to construct a protein-protein interaction network and identify the hub genes. Moreover, overall survival (OS) and disease-free survival (DFS) analysis for the hub genes was performed using the UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) online tool. Furthermore, TRRUST was used to predict the targets of the MMPs. Results Our results revealed that the transcriptional levels of MMP1, MMP9, MMP10, MMP11, MMP13, MMP14, and MMP17 were upregulated in UVM tissues compared to normal tissues. A protein-protein interaction (PPI) network was constructed and the top 50 hub genes were identified. The functions of MMPs and their neighboring proteins are mainly associated with ECM-receptor interaction, proteoglycans in cancer, the IL-17 signaling pathway, and microRNAs in cancer. Among the MMPs, MMP1/2/9/11/14/15/16/17/24 played significant roles in the progression of UVM from stage 3 to stage 4. We also found that the expression of MMP1, MMP2, MMP9, and MMP16 positively correlated with OS and DFS in patients with UVM. Additionally, 18 transcription factors associated with nine MMPs were identified. Conclusions The results of this study may provide potential biomarkers and targets for UVM. However, further studies are required to confirm these results.

show abstract

Section: Discussionmentioning

confidence: 99%

MMP1 and MMP9 are potential prognostic biomarkers and targets for uveal melanoma

et al. 2021

View full text Add to dashboard Cite

show abstract

“…ADAMTS3 is involved in the alteration of osteosarcoma matrices [ 25 ], and the single nucleotide polymorphism (SNP) of the ADAMTS3 gene is an independent prognostic biomarker for cutaneous melanoma [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer

Liang

Zhu

Chen

et al. 2020

Journal of Oncology

View full text Add to dashboard Cite

The “A Disintegrin and Metalloproteinase with Thrombospondin Motif” (ADAMTS) family of genes is involved in the occurrence and development of different cancers. However, the prognostic value of these genes in gastric cancer (GC) has not been revealed. The present study was thus conducted to determine the prognostic value for the ADAMTS family of genes in GC. First, we evaluated the mRNA expression levels of the ADAMTS family in GC patients using a GEPIA dataset. Thereafter, we determined the prognostic value of these genes by analyzing their mRNA level using the Kaplan–Meier Plotter database. The mRNA expression level of ADAMTS12 was randomly validated by qRT-PCR and meta-analysis while its coexpression genes were derived using Coexpedia. Finally, we performed Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the OmicShare Tools. Compared to normal tissues, expression of ADAMTS2 and 12 was significantly higher while that of ADAMTS1, 13, and 15 was significantly lower in GC tissues. According to the RNA-seq and gene chip data, the ADAMTS family (6, 7, 12, 15, and 18) of genes was closely related to the prognosis of GC, and their high expression levels were associated with poor prognosis and survival time. In addition, ADAMTS12 was highly expressed in 20 pairs of GC tissues based on RT-PCR (P=0.016) and meta-analysis (SMD: 0.73, 95% CI: 0.32–1.14, P<0.001). GO and KEGG pathway analyses indicated that the ADAMTS12 coexpressed genes were enriched in the pathways of extracellular matrix organization, extracellular matrix structural constituent, extracellular matrix, and protein digestion and absorption. Herein, we discovered the prognostic values and biological roles of the ADAMTS genes in GC.

show abstract

“…Finally, other regulatory mechanisms of MMP-9 expression are mediated by MMP-9 allelic variation (rs3918251GG (A>G) and by the over-expression of SOX4 responsible for the concomitant up-regulation of MMP-2/9 and NF-κB/p65 and, consequently, for a more aggressive tumor phenotype [78,79].…”

Section: Mmp-9 Functions and Regulation In Melanomamentioning

confidence: 99%

Functional Roles of Matrix Metalloproteinases and Their Inhibitors in Melanoma

Napoli

Scuderi

Gattuso

et al. 2020

Cells

View full text Add to dashboard Cite

The extracellular matrix (ECM) plays an important role in the regulation of the tissue microenvironment and in the maintenance of cellular homeostasis. Several proteins with a proteolytic activity toward several ECM components are involved in the regulation and remodeling of the ECM. Among these, Matrix Metalloproteinases (MMPs) are a class of peptidase able to remodel the ECM by favoring the tumor invasive processes. Of these peptidases, MMP-9 is the most involved in the development of cancer, including that of melanoma. Dysregulations of the MAPKs and PI3K/Akt signaling pathways can lead to an aberrant overexpression of MMP-9. Even ncRNAs are implicated in the aberrant production of MMP-9 protein, as well as other proteins responsible for the activation or inhibition of MMP-9, such as Osteopontin and Tissue Inhibitors of Metalloproteinases. Currently, there are different therapeutic approaches for melanoma, including targeted therapies and immunotherapies. However, no biomarkers are available for the prediction of the therapeutic response. In this context, several studies have tried to understand the diagnostic, prognostic and therapeutic potential of MMP-9 in melanoma patients by performing clinical trials with synthetic MMPs inhibitors. Therefore, MMP-9 may be considered a promising molecule for the management of melanoma patients due to its role as a biomarker and therapeutic target.

show abstract

Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival

Cited by 6 publications

References 47 publications

MMP1 and MMP9 are potential prognostic biomarkers and targets for uveal melanoma

MMP1 and MMP9 are potential prognostic biomarkers and targets for uveal melanoma

Prognostic Values for the mRNA Expression of the ADAMTS Family of Genes in Gastric Cancer

Functional Roles of Matrix Metalloproteinases and Their Inhibitors in Melanoma

Contact Info

Product

Resources

About