Integrated analysis of a competing endogenous RNA network reveals a ferroptosis-related 6-lncRNA prognostic signature in clear cell renal cell carcinoma.

BACKGROUND: Establishing a robust signature for prognostic prediction and precision treatment is necessary due to the heterogeneous prognosis and treatment response of clear cell renal cell carcinoma (ccRCC). OBJECTIVES: This study set out to elucidate the biological functions and prognostic role of ferroptosis-related long non-coding RNAs (lncRNAs) based on a synthetic analysis of competing endogenous RNA networks in ccRCC. MATERIAL AND METHODS: Ferroptosis-related genes were obtained from the FerrDb database. The expression data and matched clinical information of lncRNAs, miRNAs and mRNAs from The Cancer Genome Atlas (TCGA) database were obtained to identify differentially expressed RNAs. The lncRNA-miRNA-mRNA ceRNA network was established utilizing the common miRNAs that were predicted in the RNAHybrid, StarBase and TargetScan databases. Then, using progressive univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis of gene expression data and clinical information, a ferroptosis-related lncRNA prognosis signature was constructed based on the lncRNAs in ceRNA. Finally, the influence of independent lncRNAs on ccRCC was explored. RESULTS: A total of 35 ferroptosis-related mRNAs, 356 lncRNAs and 132 miRNAs were sorted out after differential expression analysis in the TCGA-KIRC. Subsequently, overlapping lncRNA-miRNA and miRNA-mRNA interactions among the RNAHybrid, StarBase and TargetScan databases were constructed and identified; then a ceRNA network with 77 axes related to ferroptosis was established utilizing mutual miRNAs in 2 interaction networks as nodes. Next, a 6-ferroptosis-lncRNA signature including PVT1, CYTOR, MIAT, SNHG17, LINC00265, and LINC00894 was identified in the training set. Kaplan-Meier analysis, PCA, t-SNE analysis, risk score curve, and receiver operating characteristic (ROC) curve were performed to confirm the validity of the signature in the training set and verified in the validation set. Finally, single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) analysis showed that the signature was related to immune cell infiltration. CONCLUSIONS: Our research underlines the role of the 6-ferroptosis-lncRNA signature as a predictor of prognosis and a therapeutic alternative for ccRCC.

Identification of the Putative Tumor Suppressor Characteristics of FAM107A via Pan-Cancer Analysis.

Family with sequence similarity 107, member A(FAM107A) was supposed as a tumor suppressor for various types of tumors. However, no pan-cancer analysis of FAM107A is available. Therefore, we conducted a FAM107A-related pan-cancer analysis across thirty-three tumors based on TCGA database to explore the molecular characteristics of FAM107A. The FAM107A expression is reduced in most cancers, and its down-regulated expression was linked to poor overall survival and progression-free survival of tumor patients. Analysis of DNA methylation of the FAM107A gene showed a negative correlation between FAM107A expression and promoter methylation in numerous cancers. Furthermore, FAM107A expression was noted to be involved in myeloid-derived suppressor cell infiltration in multiple cancers. To explore the mechanism of FAM107A in cancers, KEGG, and GO enrichment analysis was performed and the result showed "cell adhesion" and "cAMP signaling pathway" terms as the potential impact of FAM107A on cancers. An experiment in vitro showed FAM107A knockdown promoted the proliferation, migration, and invasion of bladder cancer and renal cancer cells. Our study indicates that FAM107A may be a putative tumor suppressor in bladder cancer and other tumors.

Analysis of the Mechanism of Ureproofing Technology and Postlaparoscopy on Patients with Urology and Infection.

Objective: To analyze the effect of ureteroscopy and retrolaparoscopy on urinary calculi and infection. Method: A total of 64 patients with urinary calculi and infection who received treatment in our hospital from June 2018 to January 2018 were selected. According to the different treatment methods, they were divided into two groups: a control group and a study group. The study group was treated with laparoscopic ureteroscopy, and the control group was treated with ureteroscopy. The surgical results, complications, renal function, stress response, and inflammatory reaction were compared between the two groups. Results: Compared with the control group, the study group stone clearance rate was higher, the surgical time was shorter (P < 0.05); the incidence of complications in the study group (23.3%) was lower than that in the control group (5.9%) (P < 0.05); there was no significant difference in kidney function indicators before treatment (P > 0.05); after treatment, the SCR, BUN, NGAL, and Cys-C indicators of the two groups were significantly increased. Compared with the control group, the study group change was more obvious, and the difference was statistically significant (P < 0.05); after treatment, the two sets of stress response indicators were significantly increased, but relative to the control group, the study group stress response indicator was lower (P < 0.05); before treatment, there was no significant difference in inflammatory factors (P > 0.05); after treatment, the two sets of inflammatory factor levels were significantly increased, but relative to the control group, the study group was lower (P < 0.05). Conclusion: In the clinical treatment of urinary stones, ureteroscopy technology and the laparoscopic technique have played an important role. But the laparoscopic technique is shorter, the stone clearance is higher, and the patient's renal function can be improved, and the patient is postoperative. The stress reaction should be small. Therefore, in the clinical treatment of urinary stones and infection, laparoscopic technical treatment is worth promoting.

Identification of hsa_circ_0002024 as a prognostic competing endogenous RNA (ceRNA) through the hsa_miR_129-5p/Anti-Silencing Function 1B Histone Chaperone (ASF1B) axis in renal cell carcinoma.

We aimed to identify novel circular RNAs (circRNAs) as prognostic competing endogenous RNAs (ceRNAs) to serve as genetic biomarkers and therapeutic targets for renal cell carcinoma (RCC). High-throughput sequencing data of circRNAs from Gene Expression Omnibus (GEO) and of microRNAs (miRNAs) and messenger RNAs (mRNAs) from The Cancer Genome Atlas (TCGA) were retrieved to identify differentially expressed RNAs (DERNAs). DEmRNAs were subjected to weighted gene coexpression network analysis (WGCNA) to identify prognostic DEmRNA (proDEmRNA) modules. Overlapping DEcircRNA-DEmiRNA and DEmiRNA-proDEmRNA interactions among the TargetScan, miRanda and RNAhybrid databases were constructed and identified. The circRNA-miRNA-mRNA ceRNA network was constructed using mutual DEmiRNAs in two interaction networks as nodes. mRNAs validated as significantly overexpressed in RCC by Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA) and quantitative polymerase chain reaction (q-PCR), along with the correlative miRNAs, were used for survival analysis. Finally, a ceRNA network with 13 upregulated circRNAs, 8 downregulated miRNAs and 21 upregulated mRNAs was constructed, in which Anti-Silencing Function 1B Histone Chaperone (ASF1B) and Forkhead Box M1 (FOXM1) were considered significant by Oncomine, GEPIA and q-PCR. Survival analysis showed that ASF1B, FOXM1 and hsa_miR_1254 were significantly negatively correlated but hsa_miR_129-5p was positively correlated with overall survival time. Exploration of the ceRNA network revealed the prognostic hsa_circ_0002024/hsa_miR_129-5p/ASF1B axis. Therefore, hsa_circ_0002024 was identified as a prognostic ceRNA that might sponge hsa_miR_129-5p to regulate ASF1B and affect RCC prognosis. However, further validation is needed.

A novel ferroptosis-related 12-gene signature predicts clinical prognosis and reveals immune relevancy in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is still highly aggressive and lethal even with various therapeutic approaches. As the kidney is an iron metabolism-related organ, exploring and assessing the clinical value of ferroptosis, an iron-dependent regulated cell death, is practical and important. METHODS: Prognostic ferroptosis-related differentially expressed genes (DEGs) were identified from the KIRC cohort in the cancer genome atlas (TCGA) database, from which a prognostic signature was established using Lasso-penalized Cox regression analysis. Each patient in the KIRC cohort and the E-MTAB-1980 cohort (from the ArrayExpress database) was assigned a calculated signature-correlated risk score and categorized to be either in the high- or low-risk group divided by the median risk score in the KIRC cohort. Then, the independent prognostic value of the signature was further assessed by Kaplan-Meier (K-M) survival, time-dependent receiver operating characteristic (ROC) and Cox regression analyses based on overall survival (OS) in both cohorts. Finally, risk-related DEGs were identified in both cohorts and subjected to enrichment analyses for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and immune infiltration. RESULTS: Among 60 ferroptosis-related genes, 32 prognostic DEGs were identified, from which we constructed a prognostic 12-gene signature with CARS1, HMGCR, CHAC1, GOT1, CD44, STEAP3, AKR1C1, CBS, DPP4, FANCD2, SLC1A5 and NCOA4. Patients in both cohorts were divided into high- and low-risk groups, which were visually distributed in two sets and had positive-risk-related mortality. The K-M survival and the ROC curves validated that the signature has prognostic value with P < 0.05 and area under the curve > 0.7 in both cohorts, respectively. Multivariate Cox regression further confirmed the risk score as an independent prognostic predictor for OS. Commonly enriched terms in GO and KEGG not only showed a high iron correlation but also, interestingly, immune relevance of 3 immune cells (macrophages, mast cells and regulatory T cells) and 1 immune-related function (antigen processing cell co-stimulation). CONCLUSION: We established a novel 12 ferroptosis-related-gene signature that was proven to be an independent prognostic predictor for OS and inferred to be related to tumour immunity in ccRCC; however, the underlying mechanism is still poorly characterized and needs further exploration.

AVL9 is Upregulated in and Could Be a Predictive Biomarker for Colorectal Cancer.

PURPOSE: This study aimed to explore the function and clinical significance of AVL9 in colorectal cancer (CRC). MATERIALS AND METHODS: The GEO, TCGA, and GEPIA databases were searched to evaluate the expression level of AVL9, while the SurvExpress online tool was used to explore its related clinical survival prognosis. The cBioPortal and LinkedOmics databases were used to identify AVL9 expression-related genes. Protein-protein interaction (PPI) networks were analyzed using Cytoscape 3.7.1 and DAVID6.8, which was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) signal pathway enrichment. The immunohistochemistry of AVL9 in CRC was detected using an online tool protein atlas. RNA isolation and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays were used to detect AVL9 expression in tissue and plasma samples. RESULTS: Our study confirmed that AVL9 was highly expressed in CRC lesions versus the adjacent normal tissues (P < 0.001). High AVL9 expression was negatively associated with survival outcomes (P < 0.05). GO analysis showed that AVL9 expression-related genes were enriched in single organismal cell-cell adhesion, post-transcriptional regulation of gene expression, and negative regulation of the vascular endothelial growth factor receptor signaling pathway (P < 0.05). On a KEGG pathway analysis, these genes were mainly involved in progesterone-mediated oocyte maturation, axon guidance, the insulin signaling pathway, and the ubiquitin-mediated proteolysis signaling pathways (P < 0.05). In the PPI analysis, the KBTBD2, KIAA1147, EPDR1, and RNF216 genes interacted with AVL9, and GEPIA predicted that their expression levels were all positively correlated with AVL9. Furthermore, a clinicopathological parameter analysis found that high AVL9 expression was positively correlated with differentiation and TNM stage. RT-qPCR analysis further showed that plasma AVL9 expression was upregulated in CRC patients versus healthy controls. CONCLUSION: AVL9 could serve as a potential biomarker and therapeutic target for CRC.

Dance intervention effects on physical function in healthy older adults: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Dancing is a form of physical exercise associated with health benefits in older adults. Regular dancing can prolong healthy aging, maintain or even improve physical function, and thus enhance their quality of life. The aim of this review was to evaluate the effects of dance intervention on physical function performance in healthy older adults in randomized-controlled trials (RCTs). METHODS: Five electronic databases (Cochrane Library, PsycINFO, PubMed, Scopus, and Web of Science) were searched systematically until the end of June 2018 by two independent reviewers. These searches were limited to the English language and persons with average age older than 65. The tool from the Cochrane Collaboration was used to assess the risk of bias. A standard meta-analysis was performed using Review Manager Software version 5.3. RESULTS: Thirteen RCTs from a total of 1029 older participants were included in this meta-analysis. The results showed that dance intervention significantly improved mobility function and endurance performance when compared with control groups for healthy older adults. However, gait was not significantly improved through dancing. Studies included in this review were not enough to perform meta-analysis for the effectiveness of dance on balance and general health in healthy older adults. CONCLUSION: Overall, dance intervention was effective to improve physical function performance in healthy older adults. The results from this meta-analysis strengthen the evidence from previous individual studies. Properly organized dance intervention would be a safe and effective exercise to incorporate into daily life.

Identification of cell division cycle 20 as a candidate biomarker and potential therapeutic target in bladder cancer using bioinformatics analysis.

PURPOSE: As bladder cancer (BC) is very heterogeneous and complicated in the genetic level, exploring genes to serve as biomarkers and therapeutic targets is practical. MATERIALS AND METHODS: We searched Gene Expression Omnibus (GEO) and downloaded the eligible microarray datasets. After intersection analysis for identified differentially expressed genes (DEGs) of included datasets, overlapped DEGs were identified and subsequently analyzed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Protein-Protein Interaction (PPI) and hub genes identification. Hub genes were further analyzed with mRNA expression comparation in Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) database, proteomics-based validation in The Human Protein Atlas (THPA) and survival analysis in GEO and Oncolnc database. RESULTS: We analyzed five eligible GEO datasets and identified 76 overlapped DEGs mapped into PPI network with 459 edges which were mainly enriched in cell cycle pathway and related terms in GO and KEGG analysis. Among five identified hub genes, which are Cyclin-Dependent Kinase 1 (CDK1), Ubiquitin-Conjugating Enzyme E2 C (UBE2C), Cell Division Cycle 20 (CDC20), Microtubule Nucleation Factor (TPX2) and Cell Division Cycle Associated 8 (CDCA8); CDC20 and CDCA8 were confirmed as significant in mRNA expression comparation and proteomics-based validation. However, only CDC20 was considered prognostically significant in both GEO and Oncolnc database. CONCLUSIONS: CDC20 and CDCA8 were identified as candidate diagnostic biomarkers for BC in the present study; however, only CDC20 was validated as prognostically valuable and may possibly serve as a candidate prognostic biomarker and potential therapeutic target. Still, further validation studies are essential and indispensable.

Bladder preservation approach versus radical cystectomy for high-grade non-muscle-invasive bladder cancer: a meta-analysis of cohort studies.

BACKGROUND: High-grade non-muscle-invasive bladder cancer is superficial; nonetheless, it is an aggressive cancer. Proper management strategy selection following transurethral resection between bladder preservation (BP) and radical cystectomy (RC) could result in delayed or excessive treatment. Hence, selecting the optimal treatment modality remains controversial to date. METHODS: We searched MEDLINE, The Cochrane Library, EMBASE, China National Knowledge Infrastructure, and Wanfang database through 12 April 2018. Quality and publication bias were assessed using the Newcastle-Ottawa Scale and Begg's/Egger's test. We collected 2-year, 5-year, 10-year, and 15-year survival rate and hazard ratio (HR) for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Using the Review Manager 5.2 software, we used the odds ratio (OR) of specific years and HR for meta-analysis. Subgroup analysis was performed by the original tumor state, radical cystectomy timing, bladder preservation modality, and age. RESULTS: In total, 11 cohorts with 1735 patients were selected for the meta-analysis. All OR of OS supported BP as a better treatment option; however, all OR of PFS had no significant differences. As for CSS, only the 15-year OR reflected a statistical significance preferring RC. Subgroup analysis showed that BP is more appropriate for patients older than 65 and G3 tumor. Limited data demonstrated that late RC (> 3 months) is more effective compared to early RC (< 3 months) and intravesical Bacillus Calmette-Guerin was not statistically different from that of RC. The mixed BP modalities were significantly better compared to RC in OS and worse in CSS, with both having a very low evidence strength. CONCLUSIONS: BP is a superior treatment modality compare to RC, especially for older patients and T1G3 or lower grade tumors. However, the superior BP modality was unclear. Conversely, RC could be a better option for younger patients. More specifically, late RC may be more beneficial but had a very-low-level of evidence. Quality of life should be considered equal to survival outcome; hence, post-treatment follow-up needs to be performed. Prospective randomized studies should be performed to overcome the limitations of this meta-analysis study. REGISTRATION: Registration ID is CRD42018093491 .

Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed after the disease has metastasized; it is among the most lethal forms of cancer. We recently described aberrant expression of an open reading frame 1 protein, ORF1p, encoded by long interspersed element-1 (LINE-1; L1) retrotransposon, in PDAC. To test whether LINE-1 expression leads to somatic insertions of this mobile DNA, we used a targeted method to sequence LINE-1 insertion sites in matched PDAC and normal samples. We found evidence of 465 somatic LINE-1 insertions in 20 PDAC genomes, which were absent from corresponding normal samples. In cases in which matched normal tissue, primary PDAC and metastatic disease sites were available, insertions were found in primary and metastatic tissues in differing proportions. Two adenocarcinomas secondarily involving the pancreas, but originating in the stomach and duodenum, acquired insertions with a similar discordance between primary and metastatic sites. Together, our findings show that LINE-1 contributes to the genetic evolution of PDAC and suggest that somatic insertions are acquired discontinuously in gastrointestinal neoplasms.

Dual transplantation of human neural stem cells into cervical and lumbar cord ameliorates motor neuron disease in SOD1 transgenic rats.

Stem cells provide novel sources of cell therapies for motor neuron disease that have recently entered clinical trials. In the present study, we transplanted human neural stem cells (NSCs) into the ventral horn of both the lumbar (L4-L5) and cervical (C4-C5) protuberance of SOD1 G93A rats, in an effort to test the feasibility and general efficacy of a dual grafting paradigm addressing several muscle groups in the front limbs, hind limbs and the respiratory apparatus. Transplantation was done prior to the onset of motor neuron disease. Compared with animals that had received dead NSC grafts (serving as controls), rats with live NSCs grafted at the two spinal levels lived 17 days longer. Disease onset in dually grafted animals was delayed by 10 days compared to control animals. Disease duration in NSC-grafted animals was longer by 7 days compared to controls. Our results support the potential of NSC grafts at multiple levels of spinal cord as future cellular therapy for motor neuron disease.

Mobile interspersed repeats are major structural variants in the human genome.

Characterizing structural variants in the human genome is of great importance, but a genome wide analysis to detect interspersed repeats has not been done. Thus, the degree to which mobile DNAs contribute to genetic diversity, heritable disease, and oncogenesis remains speculative. We perform transposon insertion profiling by microarray (TIP-chip) to map human L1(Ta) retrotransposons (LINE-1 s) genome-wide. This identified numerous novel human L1(Ta) insertional polymorphisms with highly variant allelic frequencies. We also explored TIP-chip's usefulness to identify candidate alleles associated with different phenotypes in clinical cohorts. Our data suggest that the occurrence of new insertions is twice as high as previously estimated, and that these repeats are under-recognized as sources of human genomic and phenotypic diversity. We have just begun to probe the universe of human L1(Ta) polymorphisms, and as TIP-chip is applied to other insertions such as Alu SINEs, it will expand the catalog of genomic variants even further.