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Genetic variants in the genes encoding rho GTPases and related regulators predict cutaneous melanoma‐specific survival
Author(s) -
Liu Shun,
Wang Yanru,
Xue William,
Liu Hongliang,
Xu Yinghui,
Shi Qiong,
Wu Wenting,
Zhu Dakai,
Amos Christopher I.,
Fang Shenying,
Lee Jeffrey E.,
Hyslop Terry,
Li Yi,
Han Jiali,
Wei Qingyi
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30785
Subject(s) - gene , melanoma , gtpase , biology , genetics , cancer research , computational biology
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 ( p trend =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.