LncRNA CARD8-AS1 suppresses lung adenocarcinoma progression by enhancing TRIM25-mediated ubiquitination of TXNRD1.

Long non-coding RNAs (lncRNAs) play crucial roles in the tumorigenesis and progression of lung adenocarcinoma (LUAD). However, little was known about the role of lncRNAs in high-risk LUAD subtypes: micropapillary-predominant adenocarcinoma (MPA) and solid-predominant adenocarcinoma (SPA). In this study, we conducted a systematic screening of differentially expressed lncRNAs using RNA sequencing in 10 paired MPA/SPA tumor tissues and adjacent normal tissues. Consequently, 110 significantly up-regulated lncRNAs and 288 aberrantly down-regulated lncRNAs were identified (|Log2 Foldchange| ≥ 1 and corrected P < 0.05). The top 10 lncRNAs were further analyzed in 89 MPA/SPA tumor tissues and 59 normal tissues from The Cancer Genome Atlas database. Among them, CARD8-AS1 showed the most significant differential expression, and decreased expression of CARD8-AS1 was significantly associated with a poorer prognosis. Functionally, CARD8-AS1 overexpression remarkably suppressed the proliferation, migration and invasion of LUAD cells both in vitro and in vivo. Conversely, inhibition of CARD8-AS1 yielded opposite effects. Mechanistically, CARD8-AS1 acted as a scaffold to facilitate the interaction between TXNRD1 and E3 ubiquitin ligase TRIM25, thereby promoting the degradation of TXNRD1 through the ubiquitin-proteasome pathway. Additionally, TXNRD1 was found to promote LUAD cell proliferation, migration and invasion in vitro. Furthermore, the suppressed progression of LUAD cells resulting from CARD8-AS1 overexpression could be significantly reversed by simultaneous overexpression of TXNRD1. In conclusion, this study revealed that the lncRNA CARD8-AS1 played a suppressive role in the progression of LUAD by enhancing TRIM25-mediated ubiquitination of TXNRD1. The CARD8-AS1-TRIM25-TXNRD1 axis may represent a promising therapeutic target for LUAD.

LncRNA PCBP1-AS1 correlated with the functional states of cancer cells and inhibited lung adenocarcinoma metastasis by suppressing the EMT progression.

The development of single-cell RNA sequencing (scRNA-seq) provided us an unprecedented chance to identify novel oncogenes or tumor suppressors at single-cell resolution. Long non-coding RNAs (lncRNAs) related to the functional states of cancer cells might play vital roles in the progression of lung adenocarcinoma (LUAD). In this study, lncRNAs that were associated with the functional states of LUAD cells identified in scRNA-seq studies were screened based on the CancerSEA database. Differential gene expression analysis and survival analysis were performed in TCGA, GEO and our JSPH databases. Finally, transwell and tail vein metastasis assays were used to reveal the functions of our identified novel prognostic lncRNAs. A total of 849 lncRNAs were initially identified. Among them, 11 lncRNAs were found significantly associated with LUAD prognosis in the TCGA database. Two of them (PCBP1-AS1 and ZSCAN16-AS1) were further validated in independent GEO datasets. ScRNA-seq analysis showed that PCBP1-AS1 and ZSCAN16-AS1 were significantly negatively correlated with most of the functional states of LUAD cells, especially with metastasis. Functionally, PCBP1-AS1 was aberrantly downregulated in LUAD cells and tumor tissues. Knockdown of PCBP1-AS1 significantly promoted the migration and invasion of LUAD cells. Consistently, PCBP1-AS1 overexpression suppressed the metastasis of LUAD in vitro and in vivo. Besides, PCBP1-AS1 inhibition induced decreased E-cadherin expression and increased N-cadherin, Vimentin and Snail expression. In conclusion, PCBP1-AS1 could suppress the metastasis of LUAD by targeting the epithelial-mesenchymal transition pathway and might serve as a prognostic biomarker and a potential therapeutic target of LUAD.

CircRNA-Cdr1as Exerts Anti-Oncogenic Functions in Bladder Cancer by Sponging MicroRNA-135a.

BACKGROUND/AIMS: CircRNAs regulate gene expression in different malignancies. However, the role of Cdr1as in the tumourigenesis of bladder cancer and its potential mechanisms remain unknown. METHODS: qRT-PCR was used to detect Cdr1as and target miRNA expression in bladder cancer tissues and cell lines. Biological functional experiments were performed to detect the effects of Cdr1as on the biological behaviour of bladder cancer cells in vivo and in vitro. Bioinformatic analysis was utilised to predict potential miRNA target sites on Cdr1as. Ago2 RNA binding protein immunoprecipitation assay, RNA antisense purification assay, biotin pull down assay and RNA FISH were performed to detect the interaction between Cdr1as and target miRNAs. Western blot was used to determine the expression level of p21 in bladder cancer cells. RESULTS: Cdr1as was significantly down-regulated in bladder cancer tissues compared with adjacent normal tissues. Overexpression of Cdr1as inhibited the proliferation, invasion and migration of bladder cancer cells in vitro and slowed down tumour growth in vivo. Cdr1as sponged multiple miRNAs in bladder cancer. Moreover, Cdr1as directly bound to miR-135a and inhibited its activity in bladder cancer. CONCLUSION: Cdr1as is down-regulated and sponges multiple miRNAs in bladder cancer. It exerts anti-oncogenic functions by sponging microRNA-135a.

MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1.

BACKGROUND/AIMS: MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. METHODS: qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2', 7'-dichlorodihydro-fluorescein diacetate, respectively. RESULTS: Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. CONCLUSIONS: MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer.

A lentiviral sponge for miRNA-21 diminishes aerobic glycolysis in bladder cancer T24 cells via the PTEN/PI3K/AKT/mTOR axis.

Cancer cells exhibit the ability to metabolise glucose to lactate even under aerobic conditions for energy. This phenomenon is known as the Warburg effect and can be a potential target to kill cancer cells. Several studies have shown evidence for interplay between microRNAs and key metabolic enzyme effecters, which can facilitate the Warburg effect in cancer cells. In the present study, a microRNA sponge forcibly expressed using a lentiviral vector was utilised to knock down miR-21 expression in vitro. qPCR and Western blot assays were performed to evaluate the expression of a regulatory factor related to aerobic glycolysis and the signalling pathway it regulates. In bladder cancer specimens, expression levels of glycolysis-related genes [glucose transporter (GLUT)1, GLUT3, lactic dehydrogenase (LDH)A, LDHB, hexokinase (HK)1, HK2, pyruvate kinase type M (PKM) and hypoxia-inducible factor 1-alpha (HIF-1α)] were higher in tumour tissues than in adjacent tissues, suggesting the role of glycolysis in bladder cancer. miR-21 inhibition in bladder cancer cell lines resulted in reduction in tumour aerobic glycolysis. Decrease in glucose uptake and lactate production was observed upon expression of the miR-21 sponge, which promoted phosphatase and tensin homologue (PTEN) expression, decreased phosphorylated AKT and deactivated mTOR. Furthermore, messenger RNA (mRNA) and protein expression levels of glycolysis-related genes were also lower in miR-21 sponge cells compared to miR-21 control cells. Our findings suggest that miR-21 acts as a molecular switch to regulate aerobic glycolysis in bladder cancer cells via the PTEN/phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway. Blocking miR-21 function can be an effective diagnostic and therapeutic approach either by itself or in combination with existing methods to treat bladder cancer.

MicroRNA-218 inhibits bladder cancer cell proliferation, migration, and invasion by targeting BMI-1.

MicroRNAs (miRNAs) are recognized as important molecules and have emerged as important gene regulators in tumorigenesis. Growing evidence suggested that miR-218 was a tumor suppressor in many human cancers. However, its underlying role in bladder cancer (BCa) remains unclear. The aim of this study was to explore the effect of miR-218 on the proliferation, migration, and invasion of BCa cells. We found that miR-218 was frequently downregulated in BCa tissues compared with normal adjacent tissues. In vitro and in vivo assays demonstrated that miR-218 overexpression in the BCa cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay showed that BMI-1 was a direct target of miR-218. In addition, we found that miR-218 regulated the expression of BMI-1 and its downstream target (PTEN) and participated in the phosphorylation of AKT. Our findings indicate that miR-218 functions as tumor suppressor in BCa, and the miR-218/BMI-1 axis may provide novel diagnostic and therapeutic strategies for the treatment of BCa.

XRCC1 polymorphisms associated with survival among Chinese bladder cancer patients receiving epirubicin and mitomycin C.

The association between DNA repair gene polymorphisms and bladder cancer risk has been widely studied. However, only few studies have examined the correlation between bladder cancer and instillation agent sensitivity. The aim of this study was to examine the association between polymorphisms of DNA repair genes, namely X-ray repair cross-complementing group I (XRCC1) rs2854509 and rs3213255, and bladder cancer recurrence risk. We recruited 244 patients (130 treated with epirubicin and 114 treated with mitomycin C). Genomic DNA was used to examine the XRCC1 rs2854509 and rs3213255 genotypes by Taqman PCR analysis. Combination analysis of XRCC1 rs2854509 and rs3213255 and examination of XRCC1 diplotypes were performed to reveal possible correlations. The rs2854509 CC and rs3213255 TT genotypes conferred shorter survival times than the rs2854509 AC/AA and rs3213255 CC/CT genotypes in patients treated with epirubicin, but not in those treated with mitomycin C (MMC) in adjusted models [hazard ratio (HR) = 0.23, 95 % confidence interval (CI) = 0.10-0.53 for rs2854509 AC + AA compared with CC; HR = 0.17, 95 % CI = 0.06-0.46 for rs3213255 CC + CT compared with TT]. Combination analysis showed significantly increased recurrence-free survival (RFS) among patients simultaneously carrying the rs2854509 AC/AA and rs3213255 CC/CT genotypes with an HR of 0.15 (95 % CI = 0.05-0.45) compared to those carrying other genotypes. Diplotype analysis demonstrated that the A-C/C-T diplotype is associated with a lower risk of recurrence compared with the common wild C-T/C-T diplotype (HR = 0.17, 95 % CI = 0.06-0.51). Our results suggest that the rs2854509 CC and rs3213255 TT genotypes confer higher sensitivity to epirubicin instillation. Moreover, the A-C/C-T diplotype presents significantly lower recurrence risk than other diplotypes.

Serum metabolomic analysis of human upper urinary tract urothelial carcinoma.

To find potential serum biomarkers for upper tract urothelial carcinomas (UTUCs) via (1)H nuclear magnetic resonance ((1)H NMR)-based metabolomic analysis. Serum specimens collected from 34 healthy individuals and 39 patients with UTUCs were subjected to (1)H NMR-based metabolomic analysis. Principal component and orthogonal partial least squares discriminant analyses were used to analyse the data. Compared with serum samples from healthy subjects, samples from UTUC patients showed elevated levels of lactate and creatinine as well as decreased levels of glucose, glutamine and taurine. Serum low-density lipoprotein/very low-density lipoprotein, valine and glycoprotein levels showed decreasing trends whereas serum polyunsaturated fatty acids and 3,7-dimethyluric acid level presented increasing trends in UTUC patients. (1)H NMR-based metabolomic analysis of serum enhances the current understanding of the mechanisms involved in UTUC development. The present analysis may be a valuable tool for UTUC detection.

Intratumor microbiome derived glycolysis-lactate signatures depicts immune heterogeneity in lung adenocarcinoma by integration of microbiomic, transcriptomic, proteomic and single-cell data.

Introduction: Microbiome plays roles in lung adenocarcinoma (LUAD) development and anti-tumor treatment efficacy. Aberrant glycolysis in tumor might promote lactate production that alter tumor microenvironment, affecting microbiome, cancer cells and immune cells. We aimed to construct intratumor microbiome score to predict prognosis of LUAD patients and thoroughly investigate glycolysis and lactate signature's association with LUAD immune cell infiltration. Methods: The Cancer Genome Atlas-LUAD (TCGA-LUAD) microbiome data was downloaded from cBioPortal and analyzed to examine its association with overall survival to create a prognostic scoring model. Gene Set Enrichment Analysis (GSEA) was used to find each group's major mechanisms involved. Our study then investigated the glycolysis and lactate pattern in LUAD patients based on 19 genes, which were correlated with the tumor microenvironment (TME) phenotypes and immunotherapy outcomes. We developed a glycolysis-lactate risk score and signature to accurately predict TME phenotypes, prognosis, and response to immunotherapy. Results: Using the univariate Cox regression analysis, the abundance of 38 genera were identified with prognostic values and a lung-resident microbial score (LMS) was then developed from the TCGA-LUAD-microbiome dataset. Glycolysis hallmark pathway was significantly enriched in high-LMS group and three distinct glycolysis-lactate patterns were generated. Patients in Cluster1 exhibited unfavorable outcomes and might be insensitive to immunotherapy. Glycolysis-lactate score was constructed for predicting prognosis with high accuracy and validated in external cohorts. Gene signature was developed and this signature was elevated in epithelial cells especially in tumor mass on single-cell level. Finally, we found that the glycolysis-lactate signature levels were consistent with the malignancy of histological subtypes. Discussion: Our study demonstrated that an 18-microbe prognostic score and a 19-gene glycolysis-lactate signature for predicting prognosis of LUAD patients. Our LMS, glycolysis-lactate score and glycolysis-lactate signature have potential roles in precision therapy of LUAD patients.

Effects of SVEP1 on Lung Squamous Cell Carcinoma and its Association with Tumor Mutation Burden, Prognosis, and Immune Regulation.

BACKGROUND: The mutated genes in lung squamous cell carcinoma were investigated for their possible association with tumor mutation burden, microsatellite instability, and cancer prognosis. OBJECTIVE: Our study aims to evaluate the value of the candidate genes as a potential biomarker of lung squamous cell carcinoma and pan-cancer analysis. METHODS: The landscape of the tumor microenvironment and infiltrating lymphocytes in lung squamous cell carcinoma was calculated using ESTIMATE and CIBERSORT algorithm. Weighed gene co-expression network analysis was used to screen key modules related to immune cell infiltration. Somatic mutations were found by data analysis from the TCGA and ICGC databases. Mann-Whitney U test was used to evaluate the tumor mutation burden difference between patients with mutant and wild-type SVEP1 genes. The Kaplan-Meier method was used to examine the prognosis of the patients with mutations. The effects of SVEP1 expression on tumor mutation burden and immunity in different cancers were determined by pan-cancer analysis. RESULTS: SVEP1 mutation was found to be associated with a higher tumor mutation burden and prognosis. SVEP1 mutation might be involved in the possible biological process of the anti-tumor immune response. SVEP1 is related to different degrees of immune infiltration in cancer. Moreover, the miRNA-SVEP1 targeting network was used to illuminate the possible mechanisms. CONCLUSION: SVEP1 mutation and its mRNA expression are related to tumor mutation burden and cancer immunity in lung squamous cell carcinoma. Our findings reveal the underlying mechanisms, indicating that SVEP1 may be a prognostic marker of lung squamous cell carcinoma.

Identification of underlying mechanisms and hub gene-miRNA networks of the genomic subgroups in preeclampsia development.

Preeclampsia is a hypertensive disorder of pregnancy that can lead to multiorgan complications in the mother and fetus. Our study aims to uncover the underlying mechanisms and hub genes between genomic subgroups of preeclampsia. A total of 180 preeclampsia cases from 4 gene profiles were classified into 3 subgroups. Weighted gene coexpression analysis was performed to uncover the genomic characteristics associated with different clinical features. Functional annotation was executed within the significant modules and hub genes were predicted using Cytoscape software. Subsequently, miRNet analysis was performed to identify potential miRNA-mRNA networks. Three key subgroup-specific modules were identified. Patients in subgroup II were found to develop more severe preeclampsia symptoms. Subgroup II, characterized by classical markers, was considered representative of typical preeclampsia patients. Subgroup I was considered as an early stage of preeclampsia with normal-like gene expression patterns. Moreover, subgroup III was a proinflammatory subgroup, which presented immune-related genomic characteristics. Subsequently, miR-34a-5p and miR-106a-5p were found to be correlated with all 3 significant gene modules. This study revealed the transcriptome classification of preeclampsia cases with unique gene expression patterns. Potential hub genes and miRNAs may facilitate the identification of therapeutic targets for preeclampsia in future.

Prediction of lung squamous cell carcinoma immune microenvironment and immunotherapy efficiency with pyroptosis-derived genes.

Lung squamous cell carcinoma (LUSC) is a common subtype of lung cancer that exhibits diverse pyroptosis regulatory patterns. Studies have highlighted the significance of pyroptosis in cancer invasion and immune responses. We aimed to explore the signatures of pyroptosis-related genes and their immune relevance in LUSC. Using The Cancer Genome Atlas (TCGA)-LUSC cohort and 5 gene expression omnibus (GEO) datasets, we performed consensus clustering based on 41 pyroptosis-related genes, and single sample gene set enrichment analysis (ssGSEA) was employed to calculate the infiltration levels of distinct clusters. A pyroptosis scoring scheme using the principal component analysis (PCA) method was used to quantify pyroptosis regulation in patients with LUSC and predict their prognosis. Four pyroptosis clusters were identified among 833 LUSC samples, which were associated with different Kyoto encyclopedia of genes and genome (KEGG) signaling pathways and tumor microenvironment infiltration features, and were highly consistent with 4 reported immune phenotypes: immune-responsive, immune-non-functional, immune-exclusion, and immune-ignorance. We then divided the patients into high- and low-pyroptosis score subgroups, and patients with higher scores were characterized by prolonged survival and attenuated immune infiltration. Moreover, higher scores were correlated with male patients, higher microsatellite instability, lower immune checkpoint inhibitor expression (such as CTLA-4 and GAL-9), and high mutation rates of typical mutated genes (e.g., TP53 and TTN). In particular, patients with lower pyroptosis scores showed better immune response to immune checkpoint inhibitor treatment. Pyroptosis regulatory patterns in the immune microenvironment can predict the clinical outcomes of patients with LUSC. Accurately quantifying the pyroptosis of individual patients will strengthen the understanding of heterogeneity within the LUSC tumor microenvironment infiltration areas.

Genome-wide analysis of methylation CpG sites in gene promoters identified four pairs of CpGs-mRNAs associated with lung adenocarcinoma prognosis.

BACKGROUND: Activation of oncogenes through promoter hypomethylation and silencing of tumor suppressor genes induced by promoter hypermethylation played essential roles in the progression of lung adenocarcinoma (LUAD). This study aimed to identify the LUAD prognostic CpG sites and the regulated genes which contributed to LUAD progression. METHODS: Methylation profiles from TCGA and GSE60645 were used to screen the differentially methylated CpGs. Then, the Log-rank test was adopted to identify LUAD prognosis-associated CpGs. Differential gene expression and survival analyses were further performed to suggest the roles of methylation-driven genes in LUAD prognosis. Finally, models and nomograms were constructed to predict the prognosis of LUAD. RESULTS: A total of 1891 CpGs at gene promoters were differentially methylated. Among them, 54 CpGs were significantly associated with LUAD prognosis. Nine of them showed significant correlations with the expression of four genes (CCDC181, CFTR, PPP1R16B, MYEOV). CCDC181, CFTR and PPP1R16B were aberrantly down-regulated in LUAD, while MYEOV was up-regulated. All of them were significantly associated with LUAD prognosis. The LASSO regression analysis indicated that tumor stages, cg09181792, cg16998150, cg22779330 and PPP1R16B were promising prognostic factors. The AUC (area under the curve) of the model containing the clinical predictors was 0.643. The combination of CpGs and PPP1R16B with clinical variables significantly improved the predictive efficiency with an AUC of 0.714 (P = 0.036). CONCLUSION: This study identified four pairs of promoter CpGs and genes that were significantly associated with LUAD prognosis. The integration of CpGs methylation and gene expression showed better predictive ability for LUAD prognosis.

Cell Trajectory-Related Genes of Lung Adenocarcinoma Predict Tumor Immune Microenvironment and Prognosis of Patients.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer which typically exhibits a diverse progression trajectory. Our study sought to explore the cell differentiation trajectory of LUAD and its clinical relevance. Methods: Utilizing a single-cell RNA-sequencing dataset (GSE117570), we identified LUAD cells of distinct differential status along with differentiation-related genes (DRGs). DRGs were applied to the analysis of bulk-tissue RNA-sequencing dataset (GSE72094) to classify tumors into different subtypes, whose clinical relevance was further analyzed. DRGs were also applied to gene co-expression network analysis (WGCNA) using another bulk-tissue RNA-sequencing dataset (TCGA-LUAD). Genes from modules that demonstrated a significant correlation with clinical traits and were differentially expressed between normal tissue and tumors were identified. Among these, genes with significant prognostic relevance were used for the development of a prognostic nomogram, which was tested on TCGA-LUAD dataset and validated in GSE72094. Finally, CCK-8, EdU, cell apoptosis, cell colony formation, and Transwell assays were used to verify the functions of the identified genes. Results: Four clusters of cells with distinct differentiation status were characterized, whose DRGs were predominantly correlated with pathways of immune regulation. Based on DRGs, tumors could be clustered into four subtypes associated with distinct immune microenvironment and clinical outcomes. DRGs were categorized into four modules. A total of nine DRGs (SFTPB, WFDC2, HLA-DPA1, TIMP1, MS4A7, HLA-DQA1, VCAN, KRT8, and FABP5) with most significant survival-predicting power were integrated to develop a prognostic model, which outperformed the traditional parameters in predicting clinical outcomes. Finally, we verified that knockdown of WFDC2 inhibited proliferation, migration, and invasion but promoted the apoptosis of A549 cells in vitro. Conclusion: The cellular composition and cellular differentiation status of tumor mass can predict the clinical outcomes of LUAD patients. It also plays an important role in shaping the tumor immune microenvironment.

Postoperative diffused alveolar hemorrhage complicated by pneumonia after lung cancer surgery in a patient with liver cirrhosis: a case report and review of literatures.

Postoperative pulmonary complications remain a challenge after pulmonary surgery in patients with severe cirrhosis in spite of advances in perioperative management. Diffused alveolar hemorrhage (DAH) is a pernicious clinical syndrome that is often primarily assumed to be atypical pneumonia. We report a case of a 54-year-old man presented with shortness of breath on the first post-operation day, who was successfully treated by left superior segmentectomy and right superior wedge resection. Imaging studies showed patchy infiltrates scattered throughout both lungs. Klebsiella pneumoniae and Candida albicans were found in the sputum culture. Management strategy was designed to provide adequate respiratory support, treat underlying infections and control inflammation. Non-invasive ventilator assisted ventilation was performed. We proposed that cirrhosis-induced DAH should be considered in the differential diagnosis of early pulmonary complications after pulmonary surgery. Early diagnosis and proper but not aggressive treatment protocol are crucial for recovery.

Extraperitoneal Laparoscopic Radical Nephroureterectomy and Lymph Node Dissection in Modified Supine Position.

OBJECTIVE: To explore the feasibility of extraperitoneal laparoscopic radical nephroureterectomy (EL-RNU) and lymph node dissection in a modified supine position for managing urothelial carcinomas in the renal pelvis or in the upper two-thirds of the ureter. PATIENTS AND METHODS: Consecutively from January 2014 to October 2015, 15 patients with high-risk urothelial carcinoma in the renal pelvis or in the upper two-thirds of the ureter underwent EL-RNU and extraperitoneal laparoscopic lymph node dissection (EL-LND). Clinical and pathologic data, histologic nodal status, perioperative complications, and recurrence data were collected. RESULTS: All of the 15 patients were treated with EL-RNU and EL-LND in a modified supine position, and none was converted to open surgery. The mean operation time was 178 ± 18 minutes. The mean estimated blood loss was 140 ± 40 mL. The mean postoperative intestinal function recovery time was 2 days. The mean postoperative hospitalization was 7 ± 1 days. Pathologic studies revealed positive lymph nodes in 3 patients (20%). The mean number of harvested lymph nodes was 12 ± 3. No local recurrence and distant metastasis were found after a median follow-up of 14.4 months (7-23 months). CONCLUSION: EL-RNU and EL-LND in the modified supine position are mini-invasive and feasible for patients with urothelial carcinoma in the renal pelvis or in the upper two-thirds of the ureter. Good exposure and dissection of the abdominal aorta and inferior vena cava and the integrity of the peritoneum are key to the operational success of this approach.

Identification of circular RNA signature in bladder cancer.

Circular RNA (circRNA) comprises a class of endogenous species of RNA consisting of a circular loop that is crucial for genetic and epigenetic regulation. The significance of circRNA in bladder cancer (BCa) remains to be investigated. Here we performed genome­wide circRNA analysis of 5 paired tumour and adjacent normal tissue samples from BCa patients via next generation sequencing (NGS) technology. Next we confirmed NGS data in a separate set of 32 paired BCa samples using quantitative real-time reverse transcription polymerase chain reaction. The results showed that circRNA profile presented a total of 88,732 circRNA in BCa samples. Among them, 14 were upregulated and 42 were downregulated with q-values of <0.001 and fold changes of ≥2 or ≤0.5. The expression level changes of hsa_circ_0091017 and hsa_circ_0002024 in the 32 paired samples were in accord with NGS data. In conclusion, we identified a set of circRNAs that are potentially implicated in the tumorigenesis of BCa and could serve as novel diagnostic markers for BCa.

Perioperative treatments for resected upper tract urothelial carcinoma: a network meta-analysis.

BACKGROUND: Perioperative treatments have been used to improve prognosis in patients with upper tract urothelial carcinoma (UTUC). However, optimal management remains unestablished. METHODS: We searched the Embase, Web of Science and Cochrane databases for studies published before June 20, 2015. All included studies were categorised into three groups on the basis of the outcome reported (overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS)). Relative hazard ratios (HRs) for death were calculated using random-effects Bayesian network meta-analysis methods. We also ranked the three different treatments in terms of three outcomes. RESULTS: A total of 31 trials with 8100 patients were included. Compared with the control, adjuvant chemotherapy (AC) could improve OS, DSS and RFS by 32% (HR 0.68, 95% CI 0.51-0.89), 29% (HR 0.71, 95% CI 0.54-0.89) and 51% (HR 0.49, 95% CI 0.23-0.85), respectively. We noted a marked prolongation of RFS in both intravesical chemotherapy (HR 0.32, 95% CI 0.09-0.69) as well as concurrent radiotherapy and intravesical chemotherapy (HR 0.32, 95% CI 0.03-0.97) than in the control. Neoadjuvant chemotherapy (NAC) showed a significant improvement in DSS relative to the control (HR 0.25, 95% CI 0.06-0.61) and a distinct advantage over AC (HR 0.36, 95% CI 0.08-0.90) or AR (HR 6.89, 95% CI 1.25-18.66). CONCLUSIONS: Our results showed that AC; intravesical chemotherapy; and concurrent radiotherapy and intravesical chemotherapy could improve the prognosis of UTUC patients. NAC was found to be more favourable for UTUC than AC in terms of DSS.

Reciprocal regulation of long noncoding RNAs THBS4­003 and THBS4 control migration and invasion in prostate cancer cell lines.

Increasing evidence implicates long noncoding RNAs (lncRNAs), a class of noncoding RNAs >200 nucleotides in length, in the development of cancer. However, the mechanism underlying the effects of lncRNAs in prostate cancer (PCa) remains to be elucidated. The present study aimed to investigate the role of lncRNA­THBS4­003 in the pathogensis of PCa. In the present study, a microarray containing 8,277 lncRNA probes and 32,207 mRNA probes were used to identify dysregulated mRNAs in three patients with PCa, and reverse transcription­quantitative polymerase chain reaction was used to determine the expression levels of thrombospondin 4 (THBS4) and lncRNA­THBS4­003 in 46 primary PCa and adjacent non­tumor tissue samples. The expression levels of THBS4 were determined in six samples of PCa and adjacent non­tumor tissues using Western blot analysis. The effects of forced THBS4 knockdown and lncRNA­THBS4­003 knockdown in the two PCa cell lines, DU145 and PC­3, were evaluated using cell migration and invasion assays, as well as using Western blot analysis. Of the 40,484 probes in the microarray, 354 were significantly upregulated (P<0.05; fold­change >2). The most significantly upregulated mRNA was THBS4. The expression levels of THBS4 and lncRNA­THBS4­003 in the 46 primary PCa samples was significantly higher, compared with that in the adjacent non­tumor tissue samples. Patients with Gleason scores >7 exhibited higher expression levels of lncRNA­THBS4­003, compared with patients with lower scores. Knockdown of THBS4 or lncRNA­THBS4­003 significantly reduced the migratory and invasive abilities of the PCa cells in vitro, and decreased the expression levels of p38 and matrix metalloproteinase (MMP)­9. These findings suggested that the reciprocal regulation of lncRNA­THBS4­003 and THBS4 contributed to the pathogenesis of PCa. Therefore silencing lncRNA­THBS4­003 or THBS4 may inhibit PCa cell migration and invasion, and regulate the levels of MMP­9 through the mitogen­activated protein kinase signaling pathway.

Association between manganese superoxide dismutase (MnSOD) polymorphism and prostate cancer susceptibility: a meta-analysis.

BACKGROUND: Previous studies have investigated the relationship between manganese superoxide dismutase (MnSOD) Val16Ala polymorphism and prostate cancer susceptibility, but the results have remained controversial. This meta-analysis was therefore performed to clarify this association. METHODS: The databases PubMed, Embase and Web of Science were searched for relevant available studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Publication bias was estimated using Begg's funnel plots and Egger's regression test. Trial sequential analysis was used to reduce the risk of type I error and estimate whether the evidence of the results was sufficient. RESULTS: Overall, a significant increased risk of prostate cancer was associated with MnSOD Val16Ala polymorphism for the heterozygote model (OR = 1.14; 95% CI, 1.05-1.24), homozygote model (OR = 1.18; 95% CI, 1.02-1.36), dominant model (OR = 1.24; 95% CI, 1.07-1.44) and recessive model (OR = 1.10; 95% CI, 0.96-1.24). In the subgroup analysis by genotyping method, the results were statistically significant for the TaqMan and PCR-RFLP methods. In addition, when stratified by sample size, statistically significant increased risks were found among both large samples and small samples. Furthermore, when stratified by source of control, significant results were detected in both population-based controls and hospital-based controls. By trial sequential analyses, these findings in the current study were shown to be based on sufficient evidence. CONCLUSIONS: This meta-analysis indicated that the Ala allele of the MnSOD gene polymorphism increases prostate cancer susceptibility.