[Association of CTLA-4 gene polymorphisms with the genetic susceptibility and prognosis of patients with Bladder urothelial carcinoma].

OBJECTIVE: To assess the association of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms with the prognosis of patients with Bladder urothelial carcinoma (BUC). METHODS: From February 2019 to October 2020, 256 BUS patients treated at the Xinxiang Central Hospital were selected as the study group, whilst 250 healthy individuals were selected as the control group. Genotypes of rs5742909 (-318C/T), rs231775 (+49A/G) and rs4553808 (-1661A/G) were determined by PCR-restriction fragment length polymorphism assay. The frequencies of genotypes and alleles of the CTLA-4 gene were compared between the two groups. All patients had undergone surgical treatment and were followed up for 3 years and divided into good prognosis group (n = 166) and poor prognosis group (n = 86) based on the status of disease. The distribution of alleles and genotypes were compared, and Kaplan-Meier analysis was used to assess the association of genetic polymorphisms with the prognosis. RESULTS: No significant difference was found in the gender, age, BMI, smoking history and alcohol use between the two groups (P > 0.05). The frequencies of GG genotype and G allele for the rs231775 (+49A/G) and rs4553808 (-1661A/G) loci were significantly higher in the study group compared with the control group (P < 0.05), whilst no statistical difference was found in the genotypic and allelic frequency for the rs5742909 locus between the two groups (P > 0.05). Among the 252 subjects who had completed follow-up, 86 had poor prognosis and 166 had good prognosis. The frequencies of GG genotype and G allele at the rs231775 (+49A/G) and rs4553808 (-1661A/G) loci were significantly lower in the good prognosis group compared with the poor prognosis group (P < 0.05). Kaplan-Meier survival curve analysis showed that the survival time of patients with GG genotype for the rs231775 (+49A/G) and rs4553808 (-1661A/G) loci was significantly shorter than patients with AA or AG genotypes (Log Rank 2 = 13.654, 9.974, P < 0.001). CONCLUSION: The polymorphisms of the rs231775 and rs4553808 loci of the CTLA-4 gene are associated with genetic susceptibility and poor prognosis for BUC, and a higher GG genotypic frequency may increase the risk for infection and poor prognosis of the patients.

Erratum: Association of 3 Common Polymorphisms of IL-27 Gene with Susceptibility to Cancer in Chinese People: Evidence from an Updated Meta-Analysis of 27 Studies.

The authors informed the journal that an error occurred in their manuscript.Figure 3C was mistakenly merged by the authors.The new version of the Figure 3C is as below.Reference:1. Meng Zhang, Xiuxiu Tan, Junjie Huang, Zekai Ke, Yukun Ge, Hu Xiong, Wei Lu, Lu Fang, Zhiming Cai, Song Wu: Association of 3 Common Polymorphisms of IL-27 Gene with Susceptibility to Cancer in Chinese: Evidence From an Updated Meta-Analysis of 27 Studies. Med Sci Monit 2015; 21: 2505-2513. DOI: 10.12659/MSM.895032.

Ligation-free technique for dorsal vascular complex control during laparoscopic radical prostatectomy: a single-center experience from China.

OBJECTIVE: To illustrate a ligation-free technique and compare perioperative and postoperative outcomes of this technique versus the standard suture method. PATIENTS AND METHODS: This study is a retrospective review of 233 consecutive patients with localized prostate cancer who underwent ligation-free technique (n = 180, Group 1) or standard ligation (n = 53, Group 2) at an academic institution from February 2010 to January 2014. RESULTS AND LIMITATIONS: Operative time was significantly shorter in Group 1 than in Group 2 (148.47 vs. 164.25 min, p = 0.000). No difference in EBL was noted between the groups (191.11 vs. 185.06 mL, p = 0.055). Postoperative continence rates at 3, 6, and 12 months in Groups 1 and 2 were 40.0 versus 24.5, 54.4 versus 37.7, and 73.9 versus 71.7 %, respectively. These differences were statistically significant. No patient in either group had a positive apical surgical margin. During follow-up, tumor recurrence or metastasis was not observed in any patient. Limitations of the study include this retrospective study of a single-center experience and lack of potency appraisal. CONCLUSIONS: This present ligation-free technique showed a statistically significant shorter interval to recovery of continence and higher continence rates in short-term postoperative results by contrast to conventional suture ligation, but no significant difference was revealed in long-term urinary control. We offer this technique and the correlative data to provide more information for deeply understanding the precise construction of the dorsal vascular complex and the mechanism of urinary control.

FK506 Binding Protein 10 Is Overexpressed and Promotes Renal Cell Carcinoma.

INTRODUCTION: FK506 binding proteins (FKBPs) function as oncogenes or tumor suppressors by interacting with steroid hormone receptors, kinases, or other cellular factors in addition to intracellular ligands FK506 and rapamycin. In this study, we aimed at evaluating the expression and function of FKBPs in renal cell carcinoma (RCC). MATERIALS AND METHODS: Thirty-four RCC specimens were analyzed by whole transcriptome sequencing. Small interfere RNA was employed to knockdown FKBP10 in 786-O and A-704 cells, and cell proliferation, cell cycle progression, invasion and migration were evaluated. RESULTS: FKBP10 was different from other members of FKBPs with most significant upregulation in almost all RCC specimens, compared to normal mucosa. FKBP10 expression was high in additional 38 RCC specimens and RCC cell lines compared to paired non-tumor tissues and normal renal tubule cells. FKBP10 knockdown led to cell cycle arrest at G0/G1 phase, and reduced cell proliferation, invasion, and migration in 786-O and A-704 cells. In addition, heat shock protein 90 was significantly downregulated after FKBP10 knockdown. CONCLUSIONS: FKBP10 is overexpressed and promotes RCC and is a new promising biomarker and therapy target for RCC.

Common Polymorphisms in the NFKBIA Gene and Cancer Susceptibility: A Meta-Analysis.

BACKGROUND: NFKBIA encodes the inhibitors of nuclear factor-κB (NF-κB), which regulate the translation of the genes involved in the inflammatory and immune reactions. Polymorphisms (rs2233406, rs3138053, and rs696) of NFKBIA have been implicated in susceptibility to many cancer types. MATERIAL AND METHODS: To evaluate the association between polymorphisms of NFKBIA and cancer susceptibility, a meta-analysis including a total of 7182 cancer cases and 10 057 controls from 28 case-control studies was performed. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Combined data demonstrated that rs3138053 polymorphism of NFKBIA was associated with cancer susceptibility in an allelic model (C vs. T: OR=10.754, 95%CI=4.175-27.697, Pheterogeneity=0.000), while the polymorphism of rs696 appeared to play a protective role in tumorigenesis (CC+CT vs. TT: OR=0.879, 95%CI=0.787-0.982, Pheterogeneity=0.107). When stratification analysis was performed by cancer type, an increased association of rs3138053 was recognized in hepatocarcinoma (C vs. T: OR=42.180, 95%CI=27.970-63.612, Pheterogeneity=0.007), while a decreased association of rs696 was identified in Hodgkin lymphoma (C vs. T: OR=0.792, 95%CI=0.656-0.956, Pheterogeneity=0.116; CC vs. TT: OR=0.658, 95%CI=0.448-0.965, Pheterogeneity=0.076; CC vs. CT+TT: OR=0.734, 95%CI=0.562-0.958, Pheterogeneity=0.347). By ethnicity, rs696 appears to be a protective candidate among Caucasians (CT vs. TT: OR=0.809, 95%CI=0.676-0.969, Pheterogeneity=0.459). CONCLUSIONS: Our data demonstrated that the rs3138053 polymorphism of NFKBIA gene is a candidate for susceptibility to overall cancers, while rs696 plays a protective role.

Association of 3 Common Polymorphisms of IL-27 Gene with Susceptibility to Cancer in Chinese: Evidence From an Updated Meta-Analysis of 27 Studies.

BACKGROUND: Many epidemiology studies have indicated that several functional polymorphisms of the IL-27 gene may contribute to individual susceptibility to cancer. Nevertheless, the data arising from these studies were inconclusive. Therefore, we conducted the current meta-analysis aiming to elucidate the effects of IL-27 polymorphisms (rs153109, rs17855750, and rs181206) on cancer susceptibility. MATERIAL AND METHODS: We searched the CNKI (Chinese National Knowledge Infrastructure), Wanfang database, PubMed, Web of Science, and Google Scholar for all eligible publications. We used odds ratios (ORs) corresponding with 95% confidence intervals (CIs) by using the random/fixed-effects model to evaluate the association. Finally, a total of 12 publications, including 27 case-control studies comprising of 7570 patients and 9839 controls, were enrolled in our meta-analysis. RESULTS: Our work demonstrates that IL-27 rs17855750 polymorphism is significantly associated with cancer susceptibility, particularly for bladder cancer. However, no association between IL-27 rs153109 and rs181206 polymorphisms and cancer susceptibility was identified. When a stratification analysis was performed by cancer type, we identified an increased susceptibility of bladder cancer in rs153109 polymorphism. Moreover, in the stratification analysis by genotyping method, we identified an increased susceptibility for PCR-RFLP group in rs17855750 polymorphism, whereas a decreased susceptibility was identified in rs153109 polymorphism. CONCLUSIONS: Our study shows that IL-27 rs17855750 polymorphism is significantly associated with increased susceptibility to cancer in Chinese.

[Corrigendum] Downregulation of nucleolar and spindle­associated protein 1 expression suppresses cell migration, proliferation and invasion in renal cell carcinoma.

Following the publication of the above article, the authors have realized that Fig. 5A was published with certain errors; essentially, the authors needed to perform further experiments to validate certain of their results, and the Blank and si­NC control data in Fig. 5A were included from an incorrect set of experiments (the intended si­NUSAP1 experimental data from the flow cytometric analyses, however, were presented correctly in the published Figure). The corrected version of Fig. 5, featuring the panels for the Blank and si­NC control data in Fig. 5A from the same set of experiments, is shown opposite. The authors have confirmed that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum. Furthermore, they apologize to the readership of the Journal for any inconvenience caused. [the original article was published in Oncology Reports 36: 1506-1516, 2016; DOI: 10.3892/or.2016.4955].

Circular RNA circSEMA5A promotes bladder cancer progression by upregulating ENO1 and SEMA5A expression.

Bladder cancer (BC) is one of the most commonly diagnosed urologic carcinomas, with high recurrence and death rates. Circular RNAs (circRNAs) are a class of noncoding RNAs which are anomalously expressed in cancers and involved in the progression of cancers. In this study, we found that circSEMA5A was upregulated in BC tissues and cell lines. The overexpressed circSEMA5A was correlated with malignant characteristics of BC. In vitro data indicated that circSEMA5A promoted proliferation, suppressed apoptosis, facilitated migration, accelerated invasion, enhanced angiogenesis and promotes glycolysis of BC. Mechanistically, circSEMA5A served as a miRNA sponge for miR-330-5p to upregulates Enolase 1 (ENO1) expression and facilitated the activation of Akt and ß-catenin signaling pathways. Then, we showed that circSEMA5A exerted its biological functions partially via miR-330-5p/ENO1 signaling. Moreover, circSEMA5A raised SEMA5A expression by recruiting EIF4A3 to enhance the mRNA stability of SEMA5A, and thereby accelerated BC angiogenesis. To sum up, circSEMA5A is upregulated in BC and facilitates BC progression by mediating miR-330-5p/ENO1 signaling and upregulating SEMA5A expression.

Downregulation of nucleolar and spindle-associated protein 1 expression suppresses cell migration, proliferation and invasion in renal cell carcinoma.

Nucleolar and spindle-associated protein 1 (NUSAP1) is a microtubule-binding protein that plays an essential role in mitosis and cancer. Previous studies have demonstrated that NUSAP1 expression is relatively elevated in several malignancies. However, the biological roles of NUSAP1 in renal cell carcinoma (RCC) remain unknown. In the present study, we firstly performed reverse transcription­polymerase chain reaction (RT-PCR) and western blot analysis to reveal that the expression of NUSAP1 was relatively elevated in clear cell RCC (ccRCC) tissue specimens and RCC cell lines. Immunohistochemical analysis showed that upregulation of NUSAP1 was significantly correlated with Fuhrman grade (P<0.001), tumor size (P=0.016), clinical stage (P<0.001) and distant metastasis (P=0.023). Additionally, high expression of NUSAP1 was closely associated with a shorter overall survival time of the ccRCC patients (P=0.006). Furthermore, we investigated the biological behaviors of RCC cells in vitro, and we identified that NUSAP1 depletion inhibited RCC cell migration, proliferation and invasion, and apoptosis was induced and the cell cycle was arrested. On the basis of our studies, NUSAP1 was identified as a potential prognostic indicator and a novel therapeutic target for RCC patients.

Rs401681 polymorphism in TERT-CLPTM1L was associated with bladder cancer risk: A meta-analysis.

OBJECTIVES: Genome-wide association studies have identified a number of genetic variants of telomerase reverse transcriptase (TERT), cleft lip and palate transmembrane1-like (CLPTM1L) associated with the risk of bladder cancer. Rs401681 polymorphism in TERT-CLPTM1L was of special interest for bladder cancer risk, whereas the results were inconclusive. MATERIALS AND METHODS: Publications illustrating the association between rs401681 polymorphism and bladder cancer risk were collected from the Embase, PubMed and Google scholar. Three independent reviewers worked on the data extraction. The meta-analysis was performed by STATA 12.0. The odds ratio (OR) with 95% confidence interval (CI) was calculated for these data. RESULTS: Six case-control studies were retrieved reporting a total of 9196 bladder cancer patients and 42570 controls. The strength of the relevance between rs401681 polymorphism and bladder cancer risk was evaluated by Stata 12.0 software. Rs401681[C] allele was identified marginally associated with increased bladder cancer risk, with per allele OR of 1.132 (95% CI=1.080-1.187, P heterogeneity=0.701); in the stratified analysis by ethnicity, the increased cancer risk was revealed in Asian and Caucasian groups. Moreover, we also revealed that rs401681 polymorphism was associated with an increased risk of bladder cancer in Asian population with three publications under allele model (OR=3.722, 95% CI=1.311-10.568, P=0.014), whereas a decreased risk was identified in homozygote model (OR=0.692, 95 % CI=0.513-0.934, P= 0.016) and recessive model (OR=0.728, 95% CI=0.541-0.980, P=0.036). CONCLUSION: In summary, our study provided evidence that rs401681 polymorphism is associated with the risk of bladder cancer.

FBXW7 overexpression suppresses renal cancer cell proliferation and induces apoptosis.

FBXW7 gene (F-box and WD-40 domain protein 7) is also named HCDC4 and is a significant tumor suppressor gene, which can regulate human cell cycle, proliferation and differentiation. In this study, we tend to investigate protein expression and related biological functions of FBXW7 gene. FBXW7 expression level in renal cell carcinoma (RCC) tissues is highly related to its clinical pathologic grade (P = 0.0094) and TNM phase (P = 0.0080) and is highly lower than in paracancerous normal tissues through immunohistochemistry study. FBXW7 high-expression patients have overall better prognosis than low-expression patients (P < 0.001). After transfected with FBXW7 plasmid, the RCC cell lines ACHN and A704 showed a depressed proliferation activity and high proportion of apoptosis through CCK8, colony formation and flow cytometry assay studies. By Western blot analysis, expression of cell proliferation-activating protein c-Myc and c-Jun is downregulated in FBXW7 high-expression RCC compared with negative control. These data suggested that FBXW7 is a significant tumor suppressor gene in RCC.