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Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival.

Publication ,  Journal Article
Xu, Y; Wang, Y; Liu, H; Shi, Q; Zhu, D; Amos, CI; Fang, S; Lee, JE; Hyslop, T; Li, X; Han, J; Wei, Q
Published in: Mol Carcinog
January 2018

Metzincins are key molecules in the degradation of the extracellular matrix and play an important role in cellular processes such as cell migration, adhesion, and cell fusion of malignant tumors, including cutaneous melanoma (CM). We hypothesized that genetic variants of the metzincin metallopeptidase family genes would be associated with CM-specific survival (CMSS). To test this hypothesis, we first performed Cox proportional hazards regression analysis to evaluate the associations between genetic variants of 75 metzincin metallopeptidase family genes and CMSS using the dataset from the genome-wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC) which included 858 non-Hispanic white patients with CM, and then validated using the dataset from the Harvard GWAS study which had 409 non-Hispanic white patients with invasive CM. Four independent SNPs (MMP16 rs10090371 C>A, ADAMTS3 rs788935 T>C, TLL2 rs10882807 T>C and MMP9 rs3918251 A>G) were identified as predictors of CMSS, with a variant-allele attributed hazards ratio (HR) of 1.73 (1.32-2.29, 9.68E-05), 1.46 (1.15-1.85, 0.002), 1.68 (1.31-2.14, 3.32E-05) and 0.67 (0.51-0.87, 0.003), respectively, in the meta-analysis of these two GWAS studies. Combined analysis of risk genotypes of these four SNPs revealed a decreased CMSS in a dose-response manner as the number of risk genotypes increased (Ptrend  < 0.001). An improvement was observed in the prediction model (area under the curve [AUC] = 81.4% vs. 78.6%), when these risk genotypes were added to the model containing non-genotyping variables. Our findings suggest that these genetic variants may be promising prognostic biomarkers for CMSS.

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Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

January 2018

Volume

57

Issue

1

Start / End Page

22 / 31

Location

United States

Related Subject Headings

  • Tolloid-Like Metalloproteinases
  • Skin Neoplasms
  • Proportional Hazards Models
  • Prognosis
  • Procollagen N-Endopeptidase
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Middle Aged
  • Melanoma
  • Matrix Metalloproteinase 9
 

Citation

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Xu, Y., Wang, Y., Liu, H., Shi, Q., Zhu, D., Amos, C. I., … Wei, Q. (2018). Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival. Mol Carcinog, 57(1), 22–31. https://doi.org/10.1002/mc.22716
Xu, Yinghui, Yanru Wang, Hongliang Liu, Qiong Shi, Dakai Zhu, Christopher I. Amos, Shenying Fang, et al. “Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival.Mol Carcinog 57, no. 1 (January 2018): 22–31. https://doi.org/10.1002/mc.22716.
Xu Y, Wang Y, Liu H, Shi Q, Zhu D, Amos CI, et al. Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival. Mol Carcinog. 2018 Jan;57(1):22–31.
Xu, Yinghui, et al. “Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival.Mol Carcinog, vol. 57, no. 1, Jan. 2018, pp. 22–31. Pubmed, doi:10.1002/mc.22716.
Xu Y, Wang Y, Liu H, Shi Q, Zhu D, Amos CI, Fang S, Lee JE, Hyslop T, Li X, Han J, Wei Q. Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival. Mol Carcinog. 2018 Jan;57(1):22–31.
Journal cover image

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

January 2018

Volume

57

Issue

1

Start / End Page

22 / 31

Location

United States

Related Subject Headings

  • Tolloid-Like Metalloproteinases
  • Skin Neoplasms
  • Proportional Hazards Models
  • Prognosis
  • Procollagen N-Endopeptidase
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Middle Aged
  • Melanoma
  • Matrix Metalloproteinase 9