Browsing by Author "Xu, Yinghui"

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    Genetic variants in the calcium signaling pathway genes are associated with cutaneous melanoma-specific survival
    (Oxford, 2019) 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; Epidemiology, School of Public Health
    Remodeling or deregulation of the calcium signaling pathway is a relevant hallmark of cancer including cutaneous melanoma (CM). In this 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, 1830 SNPs were found to be significantly associated with CM-specific survival (CMSS; P ≤ 0.050 and false-positive report probability ≤ 0.2), of which 9 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 of 1.52 (95% confidence interval = 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 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 genes encoding rho GTPases and related regulators predict cutaneous melanoma-specific survival
    (Wiley, 2017-08-15) 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; Epidemiology, School of Public Health
    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.
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    Genetic variants in the integrin signaling pathway genes predict cutaneous melanoma survival
    (Wiley, 2017-03-15) Li, Hongyu; Wang, Yanru; Liu, Hongliang; Shi, Qiong; Xu, Yinghui; Wu, Wenting; Zhu, Dakai; Amos, Christopher I.; Fang, Shenying; Lee, Jeffrey E.; Han, Jiali; Wei, Qingyi; Epidemiology, School of Public Health
    To identify genetic variants involved in prognosis of cutaneous melanoma (CM), we investigated associations of single nucleotide polymorphisms (SNPs) of genes in the integrin signaling pathway with CM survival by re-analyzing a published genome-wide association study (GWAS) from The University of Texas M.D. Anderson Cancer Center (MDACC), and then validated significant SNPs in another GWAS from Harvard University. In the MDACC study, 1,148 SNPs were significantly associated with CM-specific survival (CMSS) (P ≤ 0.050 and false-positive report probability ≤ 0.20), and nine SNPs were validated in the Harvard study (P ≤ 0.050). Among these, three independent SNPs (i.e., DOCK1 rs11018104 T>A, rs35748949 C>T and PAK2 rs1718404 C>T) showed a predictive role in CMSS, with an effect-allele attributed adjusted hazards ratio [adjHR of 1.50 (95% confidence interval (CI) = 1.18-1.90, P = 7.46E-04), 1.53 (1.18-1.97, 1.18E-03) and 0.58 (0.45-0.76, 5.60E-05), respectively]. Haplotype analysis revealed that a haplotype carrying two risk alleles A-T in DOCK1 was associated with the poorest survival in both MDACC (adjHR=1.73, 95% CI = 1.19-2.50, P = 0.004) and Harvard (adjHR = 1.95, 95% CI=1.14-3.33, P = 0.010) studies. In addition, patients with an increasing number of unfavorable genotypes (NUGs) for these three SNPs had a poorer survival. Incorporating NUGs with clinical variables showed a significantly improved ability to classify CMSS (AUC increased from 86.8% to 88.6%, P = 0.031). Genetic variants in the integrin signaling pathway may independently or jointly modulate the survival of CM patients. Further large, prospective studies are needed to validate these findings.
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    Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival
    (Wiley, 2017) 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; Department of Epidemiology, School of Public Health
    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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    Primary Caregiver Retention and Perceptions of Retention Strategies in a 36-Month Prospective Childhood Caries Study
    (Sage, 2022) Daly, Jeanette M.; Xu, Yinghui; Yanca, Emily; Levy, Steven M.; Levy, Barcey T.; Talbert, Jennifer; Tran, Jennifer L.; Keels, Martha Ann; Fontana, Margherita; Biomedical and Applied Sciences, School of Dentistry
    Introduction/objectives: This paper reports on participant retention from an ongoing prospective, multi-site cohort caries risk study involving parent/infant pairs. The objectives were to: (1) compare the retention rates at each intermediate contact (every 4 months) and dental visit (every 18 months) across the 3 clinical sites, (2) assess primary caregivers' perceptions at the end of the study about the retention efforts used in this longitudinal study, and (3) determine whether primary caregiver baseline demographic characteristics and child's baseline caries experience were associated with retention. Methods: 1325 primary caregiver-child pairs recruited at the child's first birthday were followed for 36 months at 3 sites. Dental visits occurred at children's ages of approximately 12, 30, and 48 months. Telephone/email intermediate contacts with the primary caregiver occurred 6 times between dental visits. The outcome variable was the retention rates at each dental visit and each intermediate contact. Primary caregivers' perceptions of intermediate contacts were evaluated. Retention rates were compared by maternal age, race, ethnicity, Medicaid status, yearly household income, baseline caries experience (defined as decayed, missing due to caries, or filled tooth surfaces) at 12 months, and the number of teeth erupted. Results: 1325 primary caregiver/infant pairs were enrolled and completed the first in-person dental visit, 1062 pairs (80%) completed the second visit and 985 (74%) completed the third. Most primary caregivers were female (94%), with a mean age of 29 years and 667 (50%) self-identified as White, 544 (41%) as Black, and 146 (11%) as Hispanic. The percentages of successful intermediate contacts were 95% at 4 months decreasing to 82% at 34 months. Almost all 964 (98%) of 985 primary caregivers reported at the last visit that they were comfortable/very comfortable with 4-month intermediate contacts. The multivariable analysis showed that primary caregivers who were older (OR = 1.07; 95% CI, 1.04-1.09) and White (OR = 1.52; 95% CI, 1.12-2.06) were more likely to complete the study. Conclusions: Retention strategies were focused on frequent routine contact and increasing monetary incentives. Those strategies may have resulted in retention exceeding the proposed goals. At the end of the study, primary caregivers were comfortable with the 4-month intermediate contacts.
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    Tooth Eruption and Early Childhood Caries – A Multi-site Longitudinal Study
    (American Academy of Pediatric Dentistry, 2021) Warren, John J.; Levy, Steven M.; Xu, Yinghui; Daly, Jeanette M.; Eckert, George J.; Clements, Dennis; Hara, Anderson T.; Jackson, Richard; Katz, Barry P.; Keels, Martha Ann; Levy, Barcey T.; Fontana, Margherita; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Objectives: This study assessed the relationship between the number of teeth present at 12 months and dmfs at 30 and 48 months. Methods: Data are from a longitudinal, multi-site study with clinical dental examinations conducted at 12, 30 and 48 months of age. Spearman correlation, and chi-square tests assessed relationships between teeth present at 12 months and decayed, missing or filled surfaces (dmfs) at 30 (n=1,062) and 48 months (n=985). Results: Spearman correlations were weak but significant for both 30- and 48-month time points (R= 0.066; p=0.032, R= 0.093; p=0.004, respectively). Mantel-Haenszel chi-square analyses of categories of teeth present at 12 months (0, 1–4, 5–8, and 9+) and categories of dmfs at 30 and 48 months (0, 1–2, 3–5, 6–15 and 16+), revealed non-significant (p=0.326) relationship with 30-month dmfs, but a significant (p=0.013) relationship with 48-month dmfs. Conclusion: Results suggest that early tooth eruption is weakly associated with occurrence of early childhood caries.