Browsing by Subject "melanoma-specific survival"

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    Association of genetic variants of TMEM135 and PEX5 in the peroxisome pathway with cutaneous melanoma-specific survival.
    (Annals of translational medicine, 2021-03) Wang, Haijiao; Liu, Hongliang; Dai, Wei; Luo, Sheng; Amos, Christopher I; Lee, Jeffrey E; Li, Xin; Yue, Ying; Nan, Hongmei; Wei, Qingyi

    Background

    Peroxisomes are ubiquitous and dynamic organelles that are involved in the metabolism of reactive oxygen species (ROS) and lipids. However, whether genetic variants in the peroxisome pathway genes are associated with survival in patients with melanoma has not been established. Therefore, our aim was to identify additional genetic variants in the peroxisome pathway that may provide new prognostic biomarkers for cutaneous melanoma (CM).

    Methods

    We assessed the associations between 8,397 common single-nucleotide polymorphisms (SNPs) in 88 peroxisome pathway genes and CM disease-specific survival (CMSS) in a two-stage analysis. For the discovery, we extracted the data from a published genome-wide association study from The University of Texas MD Anderson Cancer Center (MDACC). We then replicated the results in another dataset from the Nurse Health Study (NHS)/Health Professionals Follow-up Study (HPFS).

    Results

    Overall, 95 (11.1%) patients in the MDACC dataset and 48 (11.7%) patients in the NHS/HPFS dataset died of CM. We found 27 significant SNPs in the peroxisome pathway genes to be associated with CMSS in both datasets after multiple comparison correction using the Bayesian false-discovery probability method. In stepwise Cox proportional hazards regression analysis, with adjustment for other covariates and previously published SNPs in the MDACC dataset, we identified 2 independent SNPs (TMEM135 rs567403 C>G and PEX5 rs7969508 A>G) that predicted CMSS (P=0.003 and 0.031, respectively, in an additive genetic model). The expression quantitative trait loci analysis further revealed that the TMEM135 rs567403 GG and PEX5 rs7969508 GG genotypes were associated with increased and decreased levels of mRNA expression of their genes, respectively.

    Conclusions

    Once our findings are replicated by other investigators, these genetic variants may serve as novel biomarkers for the prediction of survival in patients with CM.
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    Genetic variants in ELOVL2 and HSD17B12 predict melanoma-specific survival.
    (International journal of cancer, 2019-02-08) Dai, Wei; Liu, Hongliang; Xu, Xinyuan; Ge, Jie; Luo, Sheng; Zhu, Dakai; Amos, Christopher I; Fang, Shenying; Lee, Jeffrey E; Li, Xin; Nan, Hongmei; Li, Chunying; Wei, Qingyi
    Fatty acids play a key role in cellular bioenergetics, membrane biosynthesis and intracellular signaling processes and thus may be involved in cancer development and progression. In the present study, we comprehensively assessed associations of 14,522 common single-nucleotide polymorphisms (SNPs) in 149 genes of the fatty-acid synthesis pathway with cutaneous melanoma disease-specific survival (CMSS). The dataset of 858 cutaneous melanoma (CM) patients from a published genome-wide association study (GWAS) by The University of Texas M.D. Anderson Cancer Center was used as the discovery dataset, and the identified significant SNPs were validated by a dataset of 409 CM patients from another GWAS from the Nurses' Health and Health Professionals Follow-up Studies. We found 40 noteworthy SNPs to be associated with CMSS in both discovery and validation datasets after multiple comparison correction by the false positive report probability method, because more than 85% of the SNPs were imputed. By performing functional prediction, linkage disequilibrium analysis, and stepwise Cox regression selection, we identified two independent SNPs of ELOVL2 rs3734398 T>C and HSD17B12 rs11037684 A>G that predicted CMSS, with an allelic hazards ratio of 0.66 (95% confidence interval = 0.51-0.84 and p = 8.34 × 10-4 ) and 2.29 (1.55-3.39 and p = 3.61 × 10-5 ), respectively. Finally, the ELOVL2 rs3734398 variant CC genotype was found to be associated with a significantly increased mRNA expression level. These SNPs may be potential markers for CM prognosis, if validated by additional larger and mechanistic studies.