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


ABSTRACT: 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??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.

SUBMITTER: Liu S 

PROVIDER: S-EPMC5512872 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

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