Genetic variants in the genes encoding rho GTPases and related regulators predict cutaneous melanoma-specific survival
dc.contributor.author | Liu, Shun | |
dc.contributor.author | Wang, Yanru | |
dc.contributor.author | Xue, William | |
dc.contributor.author | Liu, Hongliang | |
dc.contributor.author | Xu, Yinghui | |
dc.contributor.author | Shi, Qiong | |
dc.contributor.author | Wu, Wenting | |
dc.contributor.author | Zhu, Dakai | |
dc.contributor.author | Amos, Christopher I. | |
dc.contributor.author | Fang, Shenying | |
dc.contributor.author | Lee, Jeffrey E. | |
dc.contributor.author | Hyslop, Terry | |
dc.contributor.author | Li, Yi | |
dc.contributor.author | Han, Jiali | |
dc.contributor.author | Wei, Qingyi | |
dc.contributor.department | Epidemiology, School of Public Health | en_US |
dc.date.accessioned | 2019-05-06T18:43:00Z | |
dc.date.available | 2019-05-06T18:43:00Z | |
dc.date.issued | 2017-08-15 | |
dc.description.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 < 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. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | 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. International journal of cancer, 141(4), 721–730. doi:10.1002/ijc.30785 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/19137 | |
dc.language.iso | en_US | en_US |
dc.publisher | Wiley | en_US |
dc.relation.isversionof | 10.1002/ijc.30785 | en_US |
dc.relation.journal | International Journal of Cancer | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | GTPase-activating protein | en_US |
dc.subject | Rho GTPase | en_US |
dc.subject | Cutaneous melanoma-specific survival | en_US |
dc.subject | Genome-wide association study | en_US |
dc.title | Genetic variants in the genes encoding rho GTPases and related regulators predict cutaneous melanoma-specific survival | en_US |
dc.type | Article | en_US |