Chengyuan Gu

Lower skeletal muscle index and early complications in patients undergoing radical cystectomy for bladder cancer

BackgroundRadical cystectomy (RC) is the standard treatment for patients with muscle-invasive bladder cancer (BC), and it is also a valid option for selected patients with high-risk non-muscle-invasive BC. The purpose of this study was to evaluate the effect on the lower skeletal muscle index (SMI) of short-term postoperative complications of radical cystectomy (RC) in patients with bladder cancer (BC).MethodsA total of 247 patients who received RC for BC and 204 age-matched healthy population-based controls were retrospectively assessed. SMI was measured by preoperative computed tomography scans at the L4 to L5 level. Early complications were graded by Clavien-Dindo classification; severity of grade III or greater was identified as a severe complication. Logistic regression was utilized to determine the relationships between covariables and severe complications.ResultsA total of 125 (50.61%)/19 (7.69%) patients exhibited overall/severe complications during the early postoperative period. SMI was strongly associated with gender (P <0.01), but not age and body mass index (BMI), among patients with BC. Compared with the matched control group, BC patients exhibited lower SMI. The difference was statistically significant in the subgroup of male patients (P = 0.03). In the multivariate analysis, SMI was an independent predictor of developing severe complications. Each 1 cm2/m2 increase in SMI was associated with a decrease in the odds of morbidity by 4.8%.ConclusionsA lower SMI is frequently observed in bladder cancer patients undergoing RC and is shown to be strongly associated with early complications following surgery.

Genetic Score of Multiple Risk-Associated Single Nucleotide Polymorphisms Is a Marker for Genetic Susceptibility to Bladder Cancer

Genome‐wide association studies have identified 13 single nucleotide polymorphisms (SNPs) that are associated with bladder cancer; three of these SNPs were validated in the Chinese population. This study assessed the performance of these three SNPs, in combination, to predict genetic susceptibility to bladder cancer in Chinese. Three previously established bladder cancer risk‐associated SNPs (rs798766 in TACC3, rs9642880 in MYC, and rs2294008 in PSCA) were genotyped in 1,210 bladder cancer patients and 1,008 control subjects in Shanghai, China. A genetic score was calculated for each subject based on these three SNPs. Each of these three SNPs was significantly associated with bladder cancer risk in this independent study population, P < 0.05. The genetic score based on these three SNPs was significantly higher in cases than controls, with a mean of 1.05 and 0.99, respectively, P = 1.03E‐05. Compared with subjects with a genetic score <= 1.00, subjects with an elevated genetic score (>1.00) had a significantly increased risk for bladder cancer after adjusting for age, gender, and smoking status, OR = 1.58, 95% Confidence Interval (CI) = 1.21 − 2.06, P = 0.0007. When tested separately for lower (Ta) or higher (Tis, T1‐T4) tumor stage, the association was significantly stronger for lower (OR = 2.24, 95% CI = 1.66 − 3.01, P = 1.02E‐07) than higher tumor stage (OR = 1.33, 95% CI = 1.00 − 1.78, P = 0.05), P = 0.001. In conclusion, A combination of three previously implicated bladder cancer risk‐associated SNPs is a significant predictor of genetic susceptibility to bladder cancer in Chinese.

Polymorphisms in the mTOR Gene and Risk of Sporadic Prostate Cancer in an Eastern Chinese Population

Background The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk. Methodology/Principal Findings In a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis. Conclusions/Significances In the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted OR = 1.42 (1.13–1.78), P = 0.003 and 1.29 (1.07–1.55), P = 0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted OR = 0.76 (0.64–0.92), P = 0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted OR = 1.24 (1.04–1.47), P = 0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies.

Age-Dependent Association between Sex and Renal Cell Carcinoma Mortality: a Population-Based Analysis

Research on sex differences in renal cancer-specific mortality (RCSM), which considered the sex effect to be constant throughout life, has yielded conflicting results. This study hypothesized the sex effect may be modified by age, which is a proxy for hormonal status. Data from the Surveillance, Epidemiology and End Results database (1988–2010) were used to identify 114,539 patients with renal cell carcinoma (RCC). The study cohort was divided into three age groups using cutoffs of 42 and 58 years, which represent the premenopausal and postmenopausal periods. The cumulative incidence function and competing risks analyses were used to examine the effect of covariates on RCSM and other-cause mortality (OCM). In premenopausal period, male sex was a significant predictor of poor RCSM for both localized (adjusted subdistribution hazard ratio [aSHR] = 1.63, P = 0.002) and advanced (aSHR = 1.20, P = 0.041) disease. In postmenopausal period, the sex disparity diminished (aSHR = 1.05, P = 0.16) and reversed (aSHR = 0.95, P = 0.017) in localized and advanced disease, respectively. On the contrary, similar trend was not found for OCM across all age groups. Our results demonstrated the sex effect on RCSM was strongly modified by age. These findings may aid in clinical practice and need further evaluation of underlying biological mechanisms.

Genome-Wide Association Study of Bladder Cancer in a Chinese Cohort Reveals a New Susceptibility Locus at 5q12.3

Genome-wide association studies (GWAS) of bladder cancer have identified a number of susceptibility loci in European populations but have yet to uncover the genetic determinants underlying bladder cancer incidence among other ethnicities. Therefore, we performed the first GWAS in a Chinese cohort comprising 3,406 cases of bladder cancer and 4,645 controls. We identified a new susceptibility locus for bladder cancer at 5q12.3, located in the intron of CWC27 (rs2042329), that was significantly associated with disease risk (OR = 1.40; P = 4.61 × 10(-11)). However, rs2042329 was not associated with bladder cancer risk in patients of European descent. The rs2042329 risk allele was also related to significantly increased expression levels of CWC27 mRNA and protein in bladder cancer tissues from Chinese patients. Additional functional analyses suggested that CWC27 played an oncogenic role in bladder cancer by inducing cell proliferation and suppressing apoptosis. In conclusion, the identification of a risk-associated locus at 5q12.3 provides new insights into the inherited susceptibility to bladder cancer in Chinese populations and may help to identify high-risk individuals. Cancer Res; 76(11); 3277-84. ©2016 AACR.

Diagnosis of adults Xp11.2 translocation renal cell carcinoma by immunohistochemistry and FISH assays: clinicopathological data from ethnic Chinese population

This study aimed to assess the utility of transcription factor E3 (TFE3) break-apart fluorescence in situ hybridization (FISH) assay in diagnosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and to compare the clinicopathological features between adult Xp11.2 RCC and non-Xp11.2 RCC. 76 pathologically suspected Xp11.2 RCCs were recruited from our institution. Both TFE3 immunohistochemistry (IHC) and TFE3 FISH assay were performed for the entire cohort. The progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. FISH analysis confirmed 30 Xp11.2 RCCs, including 28 cases with positive TFE3 immunostaining and 2 cases with negative immunostaining. The false-positive and false-negative rates were 6.7% (2/30) and 4.3% (2/46), respectively, for TFE3 IHC compared with FISH assay. Xp11.2 RCC was significantly associated with higher pathological stage and Fuhrman nuclear grade compared with non-Xp11.2 RCC (P < 0.05). The median PFS and OS for TFE3 FISH-positive group were 13.0 months (95% CI, 8.4–17.6 months) and 50.0 months (95% CI, 27.6–72.4 months), respectively, while the median PFS and OS had not been reached for TFE3 FISH-negative group. In conclusion, TFE3 break-apart FISH assay is a highly useful and standard diagnostic method for Xp11.2 RCC. Adult Xp11.2 RCC is clinically aggressive and often presents at advanced stage with poor prognosis.

A functional variant in TP63 at 3q28 associated with bladder cancer risk by creating an miR-140-5p binding site.

The first genome‐wide association study (GWAS) for bladder cancer has identified a susceptibility locus at 3q28 in the European ancestry. However, the causal variant at 3q28 remains unknown. We conducted a three‐stage fine mapping study to identify potential causal variants in the region. A total of 41 single nucleotide polymorphisms (SNPs) across 120 kb at 3q28 were tested for association with bladder cancer risk among 3,094 bladder cancer cases and 3,738 controls. Resequencing and functional assays were further evaluated. The SNP rs35592567 in the 3′‐UTR of TP63 was consistently associated with bladder cancer risk in all three stages. In the combined analysis, the T allele of rs35592567 was significantly associated with a decreased risk for bladder cancer (OR = 0.82, 95% CI = 0.75–0.90, P = 9.797 × 10−6 in the additive model). Biochemical assays revealed that the T allele reduced the post‐transcriptional levels of TP63 mediated by interfering binding efficiency of miR‐140‐5p. In addition, overexpression of miR‐140‐5p inhibited bladder cancer cell proliferation and attenuated cell migration, invasion and G1 cell‐cycle arrest. Together, these results suggest that rs35592567 in TP63 may be a novel causal variant contributing to the susceptibility to bladder cancer, which provides additional insight into the pathogenesis of bladder carcinogenesis.

A single nucleotide polymorphism in ADIPOQ predicts biochemical recurrence after radical prostatectomy in localized prostate cancer

Adiponectin has been implicated in prostate cancer (PCa) aggressiveness. However, the role of genetic variations in the adiponectin (ADIPOQ) gene in PCa progression remains unknown. To determine whether genetic variants in ADIPOQ are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We evaluated three common ADIPOQ polymorphisms in 728 men with clinically localized PCa who underwent RP. Multivariable Cox proportional hazards models and Kaplan–Meier analysis were used to assess their prognostic significance on BCR. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay. ADIPOQ rs182052 variant allele was associated with both increased risk of BCR [HR: 2.44; 95% confidence interval (CI): 1.57–3.79, P = 6×10−5] and decreased adiponectin level (β = −0.048, P = 0.004). Stratified analyses demonstrated that the association was more pronounced in men with higher visceral adipose tissue. Our data support that the ADIPOQ rs182052 SNP may be a predictive biomarker for BCR after RP by a possible mechanism of altering the adiponectin level. If validated, genetic predictors of outcome may help individualizing treatment for PCa.

ADIPOQ polymorphism rs182052 is associated with clear cell renal cell carcinoma

Recent studies have indicated that low circulating adiponectin concentrations are associated with a higher risk of several cancers, including renal cell carcinoma. In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell renal cell carcinoma (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The association of serum adiponectin concentration with genetic variants was calculated using a multivariate linear regression model. A significantly higher ccRCC risk was associated with the rs182052 variant A allele (adjusted OR, 1.36 and 95% CI, 1.07–1.74 for AA vs GG, P = 0.013; adjusted OR, 1.27 and 95% CI, 1.04–1.56 for AA vs GG+AG, P = 0.019), and this positive association was more evident in overweight subjects. Fasting serum adiponectin was lower in subjects carrying A alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.

Nonlinear programming and scientific computing visualization in the optimization design of electron optical system

Abstract In part I of this paper, five different nonlinear programming methods, improved Powell method, axis directional search method with fixed step, Hook–Jeeves method, axis directional search method with variable step and Rosenbrock method, are discussed for the optimization design of electron optical systems. Major aspects of these techniques in their applications are systematically studied, which include convergence rate, optimal objective function value and global convergence. The calculation results indicate that Rosenbrock method should be recommended in electron optical system optimization. In part II of this paper, an efficient method, reverse-match interpolation method, is presented for the visualized optimization design of electron optical systems, which is a new development of CAD in electron optics. This method can produce the density distribution of electron beam from electron trajectories worked out in the optimization search process. It makes real-time control system possible.