Ran Li

Association between vascular endothelial growth factor gene polymorphisms and the risk and prognosis of renal cell carcinoma: A systematic review and meta-analysis

The aim of the meta-analysis was to clarify the associations between vascular endothelial growth factor (VEGF) polymorphisms and the risk and prognosis of renal cell carcinoma (RCC). A meta-analysis was performed by searching the databases PubMed, EMBASE and Web of Science for the relevant available studies until August 1st, 2016, and fourteen studies met the inclusion criteria. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of such associations. Besides, the pooled hazard ratios (HRs) with 95% CIs were used to evaluate the overall survival (OS). Fixed- or random-effects models were conducted according to existence of heterogeneity. Publication bias was evaluated using Beggs funnel plots and Eggers regression test. Overall, this meta-analysis included a total of 8,275 patients, who had been accrued between November 2002 and September 2015. Meta-analysis indicated that -2578C/A, +936C/T and +405G/C polymorphisms in the VEGF gene correlated with elevated RCC risk, especially in Asian populations. Moreover, VEGF -1154G/A and -634C/G polymorphisms were found significantly associated with poor OS of RCC. Therefore, this meta-analysis revealed that VEGF -2578C/A, +936C/T, +405G/C polymorphisms were associated with an elevated susceptibility to RCC, indicating that these three polymorphisms might be risk factors for RCC, especially in Asian populations.

Lack of association between NAT2 polymorphism and prostate cancer risk: a meta-analysis and trial sequential analysis

Previous studies have investigated the association between NAT2 polymorphism and the risk of prostate cancer (PCa). However, the findings from these studies remained inconsistent. Hence, we performed a meta-analysis to provide a more reliable conclusion about such associations. In the present meta-analysis, 13 independent case-control studies were included with a total of 14,469 PCa patients and 10,689 controls. All relevant studies published were searched in the databates PubMed, EMBASE, and Web of Science, till March 1st, 2017. We used the pooled odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of the association between NAT2*4 allele and susceptibility to PCa. Subgroup analysis was carried out by ethnicity, source of controls and genotyping method. Whats more, we also performed trial sequential analysis (TSA) to reduce the risk of type I error and evaluate whether the evidence of the results was firm. Firstly, our results indicated that NAT2*4 allele was not associated with PCa susceptibility (OR = 1.00, 95% CI= 0.95-1.05; P = 0.100). However, after excluding two studies for its heterogeneity and publication bias, no significant relationship was also detected between NAT2*4 allele and the increased risk of PCa, in fixed-effect model (OR = 0.99, 95% CI= 0.94-1.04; P = 0.451). Meanwhile, no significant increased risk of PCa was found in the subgroup analyses by ethnicity, source of controls and genotyping method. Moreover, TSA demonstrated that such association was confirmed in the present study. Therefore, this meta-analysis suggested that no significant association between NAT2 polymorphism and the risk of PCa was found.Previous studies have investigated the association between NAT2 polymorphism and the risk of prostate cancer (PCa). However, the findings from these studies remained inconsistent. Hence, we performed a meta-analysis to provide a more reliable conclusion about such associations. In the present meta-analysis, 13 independent case-control studies were included with a total of 14,469 PCa patients and 10,689 controls. All relevant studies published were searched in the databates PubMed, EMBASE, and Web of Science, till March 1st, 2017. We used the pooled odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of the association between NAT2*4 allele and susceptibility to PCa. Subgroup analysis was carried out by ethnicity, source of controls and genotyping method. Whats more, we also performed trial sequential analysis (TSA) to reduce the risk of type I error and evaluate whether the evidence of the results was firm. Firstly, our results indicated that NAT2*4 allele was not associated with PCa susceptibility (OR = 1.00, 95% CI= 0.95–1.05; P = 0.100). However, after excluding two studies for its heterogeneity and publication bias, no significant relationship was also detected between NAT2*4 allele and the increased risk of PCa, in fixed-effect model (OR = 0.99, 95% CI= 0.94–1.04; P = 0.451). Meanwhile, no significant increased risk of PCa was found in the subgroup analyses by ethnicity, source of controls and genotyping method. Moreover, TSA demonstrated that such association was confirmed in the present study. Therefore, this meta-analysis suggested that no significant association between NAT2 polymorphism and the risk of PCa was found.

High Annexin A5 expression promotes tumor progression and poor prognosis in renal cell carcinoma

Annexinxa0A5 has been found to act as an oncogenic protein in a variety of cancers. However, its specific biological role and mechanism in renal cell cancerxa0(RCC) remains unknown. Quantitative Real-time PCR and western blotting were used to evaluate the mRNA and protein expression level of Annexinxa0A5 in human RCC cell lines and tissues. Immunohistochemistry was adopted to measure the Annexinxa0A5 expression in 123xa0cases of RCC tissues. Survival analysis was performed to explore the association between Annexinxa0A5 expression and the prognosis of RCC. The effect of Annexinxa0A5 on RCC growth and metastasis was studied inxa0vitro and inxa0vivo. Annexinxa0A5 was frequently highly expressed in both human RCC cells and tissues. High Annexinxa0A5 expression was associated with higher clinical stage and histological grade. In addition, Annexinxa0A5 might be used as a predictive factor for the prognosis of RCC. Further research suggested that upregulated Annexinxa0A5 in RCC cells could significantly promote tumor cell proliferation, migration and invasion inxa0vitro. Subcutaneous xenograft tumor model displayed that knockdown of Annexinxa0A5 could impede tumorigenesis inxa0vivo. Moreover, mechanism study exhibited that Annexinxa0A5 could activate PI3K/Akt/mTOR signaling pathway, promote epithelial-mesenchymal transitionxa0(EMT) and the expression of MMP2 and MMP9. Annexinxa0A5 may be a potential prognostic biomarker in RCC and promotes proliferation, migration and invasion of RCC cells via activating PI3K/Akt/mTOR signaling pathway and regulating EMT process and MMP expression.

High LINC01605 expression predicts poor prognosis and promotes tumor progression via up-regulation of MMP9 in bladder cancer

The advent of high-throughput sequencing methods has facilitated identification of novel long non-coding RNAs (lncRNAs), which have been demonstrated to play an important role in multiple tumors. Moreover, with the assistance of bioinformatics analysis, LINC01605 has been found to be up-regulated in bladder cancer (BC) tissues compared with normal tissues. Hence, the present study was to explore its specific biological role and related mechanism in BC. The relative expression level of LINC01605 was measured in a cohort of BC tissues with matched normal tissues as well as human BC cell lines by quantitative real-time PCR (qRT-PCR). Survival analysis was performed to explore the relationship between LINC01605 expression and the prognosis of BC patients. The biological function of LINC01605 was studied in vitroand in vivo, by means of CCK-8 assay, colony formation assay, transwell assay, and tumor xenografts mice model. LINC01605 was found to be frequently highly expressed in both human BC cells and tissues. Survival analysis indicated that high LINC01605 expression was associated with higher histological grade and clinical stages. In addition, down-regulated LINC01605 in BC cells could significantly inhibit the abilities of proliferation, migration, and invasion in vitro and knockdown of LINC01605 in subcutaneous xenograft tumor model could impede tumorigenesis in vivo. Mechanistically, LINC01605 could activate epithelial–mesenchymal transition (EMT) signaling pathway and promote the expression of matrix metallopeptidase (MMP) 9 (MMP9). In summary, our results shed light on that LINC01605, as a new prognostic biomarker, could promote the proliferation, migration, and invasion of BC cells via activating EMT signaling pathway and up-regulating MMP9 expression.

Association between PSCA gene polymorphisms and the risk of cancer: an updated meta-analysis and trial sequential analysis

Previous studies have investigated the relationships between PSCA rs2294008 C>T and rs2976392 G>A polymorphisms and cancer susceptibility. However, the available findings remained inconsistent and even controversial. Thus, the aim of this meta-analysis was performed to clarify such associations. The online databases PubMed, EMBASE and Web of Science searched for relevant studies, covering all the papers published until September 1st, 2016. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of such associations. Then, trial sequential analysis was performed to estimate whether the evidence of the results was firm. Overall, a significant increased risk of cancer was associated with PSCA rs2294008 C>T and rs2976392 G>A polymorphisms. For the PSCA rs2294008 polymorphism, when stratified by type of cancer, the results were significant especially in gastric cancer and bladder cancer. Moreover, in the subgroup analysis by ethnicity, significant results were detected in both Asian and Caucasian populations. Similarly, for the PSCA rs2976392 polymorphism, the stratification analyses by type of cancer showed that the results were significant only in gastric cancer. In addition, the stratification analyses by ethnicity detected that this polymorphism increased cancer risk only in Asian populations. Then, trial sequential analyses demonstrated that the results of the meta-analysis were based on sufficient evidence. Therefore, this meta-analysis suggested that the PSCA rs2294008 C>T and rs2976392 G>A polymorphisms might be associated with cancer susceptibility, which might act as a potential predicted biomarker for genetic susceptibility to cancer, especially in gastric cancer and bladd er cancer.Previous studies have investigated the relationships between PSCA rs2294008 C>T and rs2976392 G>A polymorphisms and cancer susceptibility. However, the available findings remained inconsistent and even controversial. Thus, the aim of this meta-analysis was performed to clarify such associations. The online databases PubMed, EMBASE and Web of Science searched for relevant studies, covering all the papers published until September 1st, 2016. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of such associations. Then, trial sequential analysis was performed to estimate whether the evidence of the results was firm. Overall, a significant increased risk of cancer was associated with PSCA rs2294008 C>T and rs2976392 G>A polymorphisms. For the PSCA rs2294008 polymorphism, when stratified by type of cancer, the results were significant especially in gastric cancer and bladder cancer. Moreover, in the subgroup analysis by ethnicity, significant results were detected in both Asian and Caucasian populations. Similarly, for the PSCA rs2976392 polymorphism, the stratification analyses by type of cancer showed that the results were significant only in gastric cancer. In addition, the stratification analyses by ethnicity detected that this polymorphism increased cancer risk only in Asian populations. Then, trial sequential analyses demonstrated that the results of the meta-analysis were based on sufficient evidence. Therefore, this meta-analysis suggested that the PSCA rs2294008 C>T and rs2976392 G>A polymorphisms might be associated with cancer susceptibility, which might act as a potential predicted biomarker for genetic susceptibility to cancer, especially in gastric cancer and bladd er cancer.

Protective effects of sulforaphane on di-n-butylphthalate-induced testicular oxidative stress injury in male mice offsprings via activating Nrf2/ARE pathway

Di-N-butylphthalate (DBP) is one of the most common endocrine-disrupting chemicals which can disrupt human endocrine system, especially in the male reproductive system. Here, this study was aimed to determine whether sulforaphane (SFN) could protect against testicular oxidative stress injury induced by DBP in male mice offsprings. Wild-type (Nrf2+/+) and Nrf2-deficient (Nrf2-/-) timed-pregnant mice were given DBP orally from embryonic day (E)14.5 to E19.5. Subsequently, the oxidative stress markers were evaluated. Besides, Nrf2, NF-κB, I-kB, HO-1 and NQO-1 expression levels in the testis were measured by immunohistochemical staining or western blot analysis. DBP significantly reduced anogenital distance (AGD) and influenced testes growth in male mice offsprings, while SFN ameliorated these phenotypes. After DBP stimulation, the testicular morphology, testicular cell apoptosis index and the oxidative stress markers exhibited statistical differences compared with Control group, while SFN supplementation showed obvious improvements. In addition, administration of SFN could obviously increase the expression level of Nrf2 and its downstream ARE gene battery, such as HO-1, NQO-1 in the testis. Meanwhile, SFN pretreatment did not confer protection against DBP-induced testicular oxidative stress injury in Nrf2 knockout mice. Therefore, the present findings suggested that SFN could effectively protect against DBP-induced testicular oxidative stress injury through Nrf2/ARE signaling pathways in male mice offsprings.

TP53 codon 72 Polymorphism and bladder cancer risk: a meta-analysis and emphasis on the role of tumor or smoking status

Background: Various studies had explored the relationship between TP53 codon 72 polymorphisms and the risk of bladder cancer (BC). However, their results remained inconsistent and the definite role of smoking or tumor status associated with this polymorphism in BC cases was seldom involved. Hence, this meta-analysis was to disclose such associations. Methods: Systematical and comprehensive retrieval of online databases PubMed, PMC, EMBASE and Web of Science were conducted to obtain eligible studies, up to May 30th, 2018. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were utilized to assess the associations between TP53 codon 72 polymorphisms and BC susceptibilities under five genetic comparison models. Results: Ultimately, this meta-analysis enrolled 22 applicable studies with 3,791 BC cases and 4,917 controls. Our results suggested that the variant genotypes were associated with BC risk in Asian subgroup (allele model: OR=1.19, 95% CI=1.04-1.34; dominant model: OR=1.27, 95% CI=1.06-1.52; homozygote model: OR=1.36, 95% CI=1.03-1.80), while negative outcomes were presented in Caucasians. In the relationship between TP53 codon 72 polymorphisms and BC tumor stage in Asian group, positive results were presented in allele model: OR=1.68, 95% CI=1.04-2.72; dominant model: OR=2.46, 95% CI=1.08-5.61; heterozygous model: OR=2.32, 95% CI=1.04-5.14; homozygote model: OR=2.66, 95% CI=1.04-6.81. However, no evidence was revealed between this polymorphism and BC tumor grade. Besides, significant associations were displayed between TP53 codon 72 polymorphism and smoking status (allele model: OR=1.40, 95% CI=1.06-1.84; dominant model OR=1.72, 95% CI=1.18-2.50; heterozygous model: OR=1.77, 95% CI=1.19-2.64). Conclusion: Taken together, our results shed light on that TP53 codon 72 polymorphism was significantly associated with the susceptibility to BC in Asians. In addition, positive associations were also revealed between this polymorphism and tumor stage/smoking status in BC cases.

Prognostic significance of venous tumor thrombus consistency (solid vs. friable) in patients with renal cell carcinoma: A systematic review and meta-analysis

Background: To assess the prognostic value of venous tumor thrombus consistency (VTTC) in patients with renal cell carcinoma (RCC), and the association of RCC clinicopathological variables between friable venous tumor thrombus (VTT) and solid VTT. n Methods: Relevant studies were systematically searched from the databases PubMed, EMBASE, Web of Science and the Cochrane Library up to December 1st, 2017. Data was centrally extracted and analyzed from the previous studies by two independent reviewers. The pooled hazard ratio (HR) and its 95% confidence intervals (CI) were calculated to assess the prognostic impact of VTTC on RCC patients. Besides, the associations between VTTC and clinical parameters of RCC were calculated using the pooled odds ratio (OR) with 95% CI. n Results: Overall, friable VTT is an important adverse predictor of OS in patients with RCC using the Fixed-effort model (pooled HR =1.60; 95% CI, 1.13–2.26). Nevertheless, the results showed that friable VTT was not a significant predictor of CSS in patients with RCC (pooled HR =1.32; 95% CI, 0.88–1.99). Besides, this meta-analysis also investigated the association of RCC clinicopathological variables between friable VTT and solid VTT. Of the selected variables, nodal status, perinephric fat invasion, tumor necrosis, Fuhrman grade, pathologic grade and histological subtype were associated with VTTC. n Conclusions: This meta-analysis indicated a friable VTT might significantly affect the prognosis of the RCC patients with VTTC.

RTA-408 Protects Kidney from Ischemia-Reperfusion Injury in Mice via Activating Nrf2 and Downstream GSH Biosynthesis Gene

Acute kidney injury (AKI) induced by ischemia-reperfusion is a critical conundrum in many clinical settings. Here, this study aimed to determine whether and how RTA-408, a novel oleanane triterpenoid, could confer protection against renal ischemia-reperfusion injury (IRI) in male mice. Mice treated with RTA-408 undergoing unilateral ischemia followed by contralateral nephrectomy had improved renal function and histological outcome, as well as decreased apoptosis, ROS production, and oxidative injury marker compared with vehicle-treated mice. Also, we had found that RTA-408 could strengthen the total antioxidant capacity by increasing Nrf2 nuclear translocation and subsequently increased Nrf2 downstream GSH-related antioxidant gene expression and activity. In vitro study demonstrated that GSH biosynthesis enzyme GCLc could be an important target of RTA-408. Furthermore, Nrf2-deficient mice treated with RTA-408 had no significant improvement in renal function, histology, ROS production, and GSH-related gene expression. Thus, by upregulating Nrf2 and its downstream antioxidant genes, RTA-408 presents a novel and potential approach to renal IRI prevention and therapy.

Association between 8q24 Gene Polymorphisms and the Risk of Prostate Cancer: A Systematic Review and Meta-Analysis

Though numerous studies have been conducted to investigate the associations between five 8q24 polymorphisms (rs6983267 T>G, rs1447295 C>A, rs16901979 C>A, rs6983561 A>C and rs10090154 C>T) and prostate cancer (PCa) risk, the available results remained contradictory. Therefore, we performed a comprehensive meta-analysis to derive a precise estimation of such associations. We searched electronic databases PubMed, EMBASE, Web of Science and Wan Fang for the relevant available studies up to February 1st, 2017, and 39 articles were ultimately adopted in this meta-analysis. All data were extracted independently by two investigators and recorded in a unified form. The strength of association between 8q24 polymorphisms and PCa susceptibility was evaluated by the pooled odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analysis was conducted based on ethnicity, source of controls and genotypic method. Overall, a total of 39 articles containing 80 studies were adopted in this meta-analysis. The results of this meta-analysis indicated that five 8q24 polymorphisms above were all related to PCa susceptibility. Besides, in the subgroup analysis by ethnicity, all selected 8q24 polymorphisms were significantly associated with PCa risk in Asian population. In addition, stratification analysis by source of controls showed that significant results were mostly concentrated in the studies controls from general population. Moreover, when stratified by genotypic method, significant increased PCa risks were found by TaqMan method. Therefore, this meta-analysis demonstrated that 8q24 polymorphisms (rs6983267 T>G, rs1447295 C>A, rs16901979 C>A, rs6983561 A>C and rs10090154 C>T) were associated with the susceptibility to PCa, which held the potential biomarkers for PCa risk.