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Genetic variants in the genes encoding rho GTPases and related regulators predict cutaneous melanoma-specific survival.

Publication ,  Journal Article
Liu, S; Wang, Y; Xue, W; Liu, H; Xu, Y; Shi, Q; Wu, W; Zhu, D; Amos, CI; Fang, S; Lee, JE; Hyslop, T; Li, Y; Han, J; Wei, Q
Published in: Int J Cancer
August 15, 2017

Rho GTPases control cell division, motility, adhesion, vesicular trafficking and phagocytosis, which may affect progression and/or prognosis of cancers. Here, we investigated associations between genetic variants of Rho GTPases-related genes and cutaneous melanoma-specific survival (CMSS) by re-analyzing a published melanoma genome-wide association study (GWAS) and validating the results in another melanoma GWAS. In the single-locus analysis of 36,018 SNPs in 129 Rho-related genes, 427 SNPs were significantly associated with CMSS (p < 0.050 and false-positive report probability <0.2) in the discovery dataset, and five SNPs were replicated in the validation dataset. Among these, four SNPs (i.e., RHOU rs10916352 G > C, ARHGAP22 rs3851552 T > C, ARHGAP44 rs72635537 C > T and ARHGEF10 rs7826362 A > T) were independently predictive of CMSS (a meta-analysis derived p = 9.04 × 10-4 , 9.58 × 10-4 , 1.21 × 10-4 and 8.47 × 10-4 , respectively). Additionally, patients with an increasing number of unfavorable genotypes (NUGs) of these loci had markedly reduced CMSS in both discovery dataset and validation dataset (ptrend =1.47 × 10-7 and 3.12 × 10-5 ). The model including the NUGs and clinical variables demonstrated a significant improvement in predicting the five-year CMSS. Moreover, rs10916352C and rs3851552C alleles were significantly associated with an increased mRNA expression levels of RHOU (p = 1.8 × 10-6 ) and ARHGAP22 (p = 5.0 × 10-6 ), respectively. These results may provide promising prognostic biomarkers for CM personalized management and treatment.

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

August 15, 2017

Volume

141

Issue

4

Start / End Page

721 / 730

Location

United States

Related Subject Headings

  • rho GTP-Binding Proteins
  • Survival Analysis
  • Skin Neoplasms
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Melanoma, Cutaneous Malignant
  • Melanoma
  • Male
  • Humans
  • Genetic Predisposition to Disease
 

Citation

APA
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Liu, S., Wang, Y., Xue, W., Liu, H., Xu, Y., Shi, Q., … Wei, Q. (2017). Genetic variants in the genes encoding rho GTPases and related regulators predict cutaneous melanoma-specific survival. Int J Cancer, 141(4), 721–730. https://doi.org/10.1002/ijc.30785
Liu, Shun, Yanru Wang, William Xue, Hongliang Liu, Yinghui Xu, Qiong Shi, Wenting Wu, et al. “Genetic variants in the genes encoding rho GTPases and related regulators predict cutaneous melanoma-specific survival.Int J Cancer 141, no. 4 (August 15, 2017): 721–30. https://doi.org/10.1002/ijc.30785.
Liu S, Wang Y, Xue W, Liu H, Xu Y, Shi Q, et al. Genetic variants in the genes encoding rho GTPases and related regulators predict cutaneous melanoma-specific survival. Int J Cancer. 2017 Aug 15;141(4):721–30.
Liu, Shun, et al. “Genetic variants in the genes encoding rho GTPases and related regulators predict cutaneous melanoma-specific survival.Int J Cancer, vol. 141, no. 4, Aug. 2017, pp. 721–30. Pubmed, doi:10.1002/ijc.30785.
Liu S, Wang Y, Xue W, Liu H, Xu Y, Shi Q, Wu W, Zhu D, Amos CI, Fang S, Lee JE, Hyslop T, Li Y, Han J, Wei Q. Genetic variants in the genes encoding rho GTPases and related regulators predict cutaneous melanoma-specific survival. Int J Cancer. 2017 Aug 15;141(4):721–730.

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

August 15, 2017

Volume

141

Issue

4

Start / End Page

721 / 730

Location

United States

Related Subject Headings

  • rho GTP-Binding Proteins
  • Survival Analysis
  • Skin Neoplasms
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Melanoma, Cutaneous Malignant
  • Melanoma
  • Male
  • Humans
  • Genetic Predisposition to Disease