Browsing by Author "Xu, Yinghui"

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    Genetic variant of IRAK2 in the toll-like receptor signaling pathway and survival of non-small cell lung cancer.
    (International journal of cancer, 2018-11) Xu, Yinghui; Liu, Hongliang; Liu, Shun; Wang, Yanru; Xie, Jichun; Stinchcombe, Thomas E; Su, Li; Zhang, Ruyang; Christiani, David C; Li, Wei; Wei, Qingyi
    The toll-like receptor (TLR) signaling pathway plays an important role in the innate immune responses and antigen-specific acquired immunity. Aberrant activation of the TLR pathway has a significant impact on carcinogenesis or tumor progression. Therefore, we hypothesize that genetic variants in the TLR signaling pathway genes are associated with overall survival (OS) of patients with non-small cell lung cancer (NSCLC). To test this hypothesis, we first performed Cox proportional hazards regression analysis to evaluate associations between genetic variants of 165 TLR signaling pathway genes and NSCLC OS using the genome-wide association study (GWAS) dataset from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). The results were further validated by the Harvard Lung Cancer Susceptibility GWAS dataset. Specifically, we identified IRAK2 rs779901 C > T as a predictor of NSCLC OS, with a variant-allele (T) attributed hazards ratio (HR) of 0.78 [95% confidence interval (CI) = 0.67-0.91, P = 0.001] in the PLCO dataset, 0.84 (0.72-0.98, 0.031) in the Harvard dataset, and 0.81 (0.73-0.90, 1.08x10-4 ) in the meta-analysis of these two GWAS datasets. In addition, the T allele was significantly associated with an increased mRNA expression level of IRAK2. Our findings suggest that IRAK2 rs779901 C > T may be a promising prognostic biomarker for NSCLC OS.
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    Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival.
    (International journal of cancer, 2018-06) Li, Bo; Wang, Yanru; Xu, Yinghui; Liu, Hongliang; Bloomer, Wendy; Zhu, Dakai; Amos, Christopher I; Fang, Shenying; Lee, Jeffrey E; Li, Xin; Han, Jiali; Wei, Qingyi
    Cutaneous melanoma (CM) is considered as a steroid hormone-related malignancy. However, few studies have evaluated the roles of genetic variants encoding steroid hormone receptor genes and their related regulators (SHR-related genes) in CM-specific survival (CMSS). Here, we performed a pathway-based analysis to evaluate genetic variants of 191 SHR-related genes in 858 CMSS patients using a dataset from a genome-wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC), and then validated the results in an additional dataset of 409 patients from the Harvard GWAS. Using multivariate Cox proportional hazards regression analysis, we identified three-independent SNPs (RORA rs782917 G > A, RORA rs17204952 C > T and DNMT1 rs7253062 G > A) as predictors of CMSS, with a variant-allele attributed hazards ratio (HR) and 95% confidence interval of 1.62 (1.25-2.09), 1.60 (1.20-2.13) and 1.52 (1.20-1.94), respectively. Combined analysis of risk genotypes of these three SNPs revealed a decreased CMSS in a dose-response manner as the number of risk genotypes increased (ptrend  < 0.001); however, no improvement in the prediction model was observed (area under the curve [AUC] = 79.6-80.8%, p = 0.656), when these risk genotypes were added to the model containing clinical variables. Our findings suggest that genetic variants of RORA and DNMT1 may be promising biomarkers for CMSS, but these results needed to be validated in future larger studies.
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    Genetic variants in the calcium signaling pathway genes are associated with cutaneous melanoma-specific survival.
    (Carcinogenesis, 2018-12-29) Wang, Xiaomeng; Liu, Hongliang; Xu, Yinghui; Xie, Jichun; Zhu, Dakai; Amos, Christopher I; Fang, Shenying; Lee, Jeffrey E; Li, Xin; Nan, Hongmei; Song, Yanqiu; Wei, Qingyi
    Remodeling or deregulation of the calcium signaling pathway is a relevant hallmark of cancer including cutaneous melanoma (CM). In the present study, using data from a published genome-wide association study (GWAS) from The University of Texas M.D. Anderson Cancer Center, we assessed the role of 41,377 common single nucleotide polymorphisms (SNPs) of 167 calcium signaling pathway genes in CM survival. We used another GWAS from Harvard University as the validation dataset. In the single-locus analysis, 1,830 SNPs were found to be significantly associated with CM-specific survival (CMSS) (P ≤ 0.050 and false-positive report probability ≤ 0.2), of which nine SNPs were validated in the Harvard study (P ≤ 0.050). Among these, three independent SNPs (i.e., PDE1A rs6750552 T>C, ITPR1 rs6785564 A>G and RYR3 rs2596191 C>A) had a predictive role in CMSS, with a meta-analysis derived hazards ratio (HR) of 1.52 [95% confidence interval (CI) = 1.19-1.94, P = 7.21×10-4]], 0.49 (0.33-0.73, 3.94×10-4) and 0.67 (0.53-0.86, 0.0017), respectively. Patients with an increasing number of protective genotypes had remarkably improved CMSS. Additional expression quantitative trait loci (eQTL) analysis showed that these genotypes were also significantly associated with mRNA expression levels of the genes. Taken together, these results may help us to identify prospective biomarkers in the calcium signaling pathway for CM prognosis.
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    Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival.
    (Molecular carcinogenesis, 2018-01) Xu, Yinghui; Wang, Yanru; Liu, Hongliang; Shi, Qiong; Zhu, Dakai; Amos, Christopher I; Fang, Shenying; Lee, Jeffrey E; Hyslop, Terry; Li, Xin; Han, Jiali; Wei, Qingyi
    Metzincins are key molecules in the degradation of the extracellular matrix and play an important role in cellular processes such as cell migration, adhesion, and cell fusion of malignant tumors, including cutaneous melanoma (CM). We hypothesized that genetic variants of the metzincin metallopeptidase family genes would be associated with CM-specific survival (CMSS). To test this hypothesis, we first performed Cox proportional hazards regression analysis to evaluate the associations between genetic variants of 75 metzincin metallopeptidase family genes and CMSS using the dataset from the genome-wide association study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC) which included 858 non-Hispanic white patients with CM, and then validated using the dataset from the Harvard GWAS study which had 409 non-Hispanic white patients with invasive CM. Four independent SNPs (MMP16 rs10090371 C>A, ADAMTS3 rs788935 T>C, TLL2 rs10882807 T>C and MMP9 rs3918251 A>G) were identified as predictors of CMSS, with a variant-allele attributed hazards ratio (HR) of 1.73 (1.32-2.29, 9.68E-05), 1.46 (1.15-1.85, 0.002), 1.68 (1.31-2.14, 3.32E-05) and 0.67 (0.51-0.87, 0.003), respectively, in the meta-analysis of these two GWAS studies. Combined analysis of risk genotypes of these four SNPs revealed a decreased CMSS in a dose-response manner as the number of risk genotypes increased (Ptrend  < 0.001). An improvement was observed in the prediction model (area under the curve [AUC] = 81.4% vs. 78.6%), when these risk genotypes were added to the model containing non-genotyping variables. Our findings suggest that these genetic variants may be promising prognostic biomarkers for CMSS.
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    Genetic variants of genes in the Notch signaling pathway predict overall survival of non-small cell lung cancer patients in the PLCO study.
    (Oncotarget, 2016-09) Xu, Yinghui; Wang, Yanru; Liu, Hongliang; Kang, Xiaozheng; Li, Wei; Wei, Qingyi
    The Notch signaling pathway has been shown to have biological significance and therapeutic application in non-small cell lung cancer (NSCLC). We hypothesize that genetic variants of genes in the Notch signaling pathway are associated with overall survival (OS) of NSCLC patients. To test this hypothesis, we performed multivariate Cox proportional hazards regression analysis to evaluate associations of 19,571 single nucleotide polymorphisms (SNPs) in 132 Notch pathway genes with OS of 1,185 NSCLC patients available from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We found that five potentially functional tagSNPs in four genes (i.e., ADAM12 rs10794069 A > G, DTX1 rs1732793 G > A, TLE1 rs199731120 C > CA, TLE1 rs35970494 T > TC and E2F3 rs3806116 G > T) were associated with a poor OS, with a variant-allele attributed hazards ratio (HR) of 1.27 [95% confidence interval (95% CI) = 1.13-1.42, P = 3.62E-05], 1.30 (1.14-1.49, 8.16E-05), 1.40 (1.16-1.68, 3.47E-04), 1.27 (1.11-1.44, 3.38E-04), and 1.21 (1.09-1.33, 2.56E-04), respectively. Combined analysis of these five risk genotypes revealed that the genetic score 0-5 was associated with the adjusted HR in a dose-response manner (Ptrend = 3.44E-13); individuals with 2-5 risk genotypes had an adjusted HR of 1.56 (1.34-1.82, 1.46E-08), compared with those with 0-1 risk genotypes. Larger studies are needed to validate our findings.