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Abstract Clear cell renal cell carcinoma (ccRCC) poses clinical challenges due to its varied prognosis, tumor microenvironment attributes, and responses to immunotherapy. We established a novel Programmed Cell Death-related Signature (PRS) for ccRCC assessment, derived through the Least Absolute Shrinkage and Selection Operator (LASSO) regression method. We validated PRS using the E-MTAB-1980 dataset and created PCD-related clusters via non-negative matrix factorization (NMF). Our investigation included an in-depth analysis of immune infiltration scores using various algorithms. Additionally, we integrated data from the Cancer Immunome Atlas (TCIA) for ccRCC immunotherapy insights and leveraged the Genomics of Drug Sensitivity in Cancer (GDSC) database to assess drug sensitivity models. We complemented our findings with single-cell sequencing data and employed the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and qRT-PCR to compare gene expression profiles between cancerous and paracancerous tissues. PRS serves as a valuable tool for prognostication, immune characterization, tumor mutation burden estimation, immunotherapy response prediction, and drug sensitivity assessment in ccRCC. We identify five genes with significant roles in cancer promotion and three genes with cancer-suppressive properties, further validated by qRT-PCR and CPTAC analyses, showcasing gene expression differences in ccRCC tissues. Our study introduces an innovative PCD model that amalgamates diverse cell death patterns to provide accurate predictions for clinical outcomes, mutational profiles, and immune characteristics in ccRCC. Our findings hold promise for advancing personalized treatment strategies in ccRCC patients.

ObjectiveComparing the specific advantages and surgical outcomes of each step in radical prostatectomy under 3D vs. 2D laparoscopy.MethodsFrom October 2019 to January 2023, our urology department treated 63 cases of prostate cancer, using an odd-even arrangement method to divide into two groups. This is a non-randomized prospective study, with 33 odd-numbered cases in the 3D group and 30 even-numbered cases in the 2D group. The surgery was divided into four steps: (1) establishing an extraperitoneal pneumoperitoneum (2) pelvic lymph node dissection (3)excising the prostate (4)bladder-urethral anastomosis, comparing the two groups in terms of surgical time, blood loss, and relevant postoperative indicators for each step.ResultsAll 63 surgeries were successfully completed without any conversions. Comparing 3D and 2D laparoscopy groups, there were statistically significant differences in total surgery time (123.5 ± 15.3 min vs. 145.6 ± 17.2 min, P 0.05). In terms of urinary incontinence rates, the 3D laparoscopy group was lower than the 2D group, and in terms of preserving erectile function, the 3D group was higher than the 2D group, with significant statistical differences (P 0.05).ConclusionCompared to traditional 2D laparoscopy, 3D laparoscopy can shorten the operation time and reduce bleeding in the steps of prostate excision and bladder-urethral anastomosis, but there was no significant difference in peri-operative outcomes.

The widespread application of zinc oxide nanoparticles (ZnO NPs) in our daily life has initiated an enhanced awareness of their biosafety concern. An incredible boom of evidence of organismal disorder has accumulated for ZnO NPs, yet there has been no relevant study at the single-cell level. Here, we profiled > 28,000 single-cell transcriptomes and assayed > 25,000 genes in testicular tissues from two healthy Sprague Dawley (SD) rats and two SD rats orally exposed to ZnO NPs. We identified 10 cell types in the rat testis. ZnO NPs had more deleterious effects on spermatogonia, Sertoli cells, and macrophages than on the other cell types. Cell–cell communication analysis indicated a sharp decrease of interaction intensity for all cell types except macrophages in the ZnO NPs group than in the control group. Interestingly, two distinct maturation states of spermatogonia were detected during pseudotime analysis, and ZnO NPs induced reservoir exhaustion of undifferentiated spermatogonia. Mechanically, ZnO NPs triggered fatty acid accumulation in GC-1 cells through protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling and peroxisome proliferator-activated receptor alpha (PPARα)/acyl‐CoA oxidase 1 (Acox1) axis, contributing to cell apoptosis. In terms of Sertoli cells, downregulated genes were highly enriched for tight junction. In vitro and in vivo experiments verified that ZnO NPs disrupted blood-testis barrier formation and growth factors synthesis, which subsequently inhibited the proliferation and induced the apoptosis of spermatogonia. As for the macrophages, ZnO NPs activated oxidative stress of Raw264.7 cells through nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and promoted cell apoptosis through extracellular signal-regulated kinase (ERK) 1/2 pathway. Collectively, our work reveals the cell type-specific and cellularly heterogenetic mechanism of ZnO NPs-induced testis damage and paves the path for identifying putative biomarkers and therapeutics against this disorder.

Summary: O-GlcNAc transferase (OGT) acts in the development of various cancers, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we found that OGT was upregulated in ccRCC and this upregulation was associated with a worse survival. Moreover, OGT promoted the proliferation, clone formation, and invasion of VHL-mutated ccRCC cells. Mechanistically, OGT increased the protein level of hypoxia-inducible factor-2α (HIF-2α) (the main driver of the clear cell phenotype) by repressing ubiquitin‒proteasome system-mediated degradation. Interestingly, the OGT/HIF-2α axis conferred ccRCC a high sensitivity to ferroptosis. In conclusion, OGT promotes the progression of VHL-mutated ccRCC by inhibiting the degradation of HIF-2α, and agents that can modulate the OGT/HIF-2α axis may exert therapeutic effects on mutated VHL ccRCC.

Abstract Hydatid cyst (HC) is a zoonotic parasitic disease in agricultural and pastoral areas while renal involvement without liver and lung hydatid is both less common in clinical practice and rarely described in literature. We present a case of a 40‐year‐old male from Xinjiang who complained of flank pain in the right with oliguria. Robot‐assisted laparoscopic exploration, conversion to open laparotomy and excision of internal capsule in right kidney were performed. Finally, a typical renal HC was diagnosed after complementary examinations. Isolated renal HC is very rare and can be misinterpreted as a cystic renal cell carcinoma pre‐operatively.

Hypospadias and cryptorchidism are the most common congenital malformations in male neonates, both of which are also the important clinical manifestations of testicular dysgenesis syndrome and share a same origin. Many studies have suggested that prenatal exposure to endocrine-disrupting chemicals (EDCs) is associated with hypospadias and cryptorchidism development. However, the consistent mechanisms remain unclear. To identify the key EDCs, genes and biological networks related to the development of hypospadias and cryptorchidism respectively and commonly, we conduct the present study and found a new method for predicting the correlation between the interactive genes of hypospadias/cryptorchidism and chemicals. Transcriptome profiles were obtained from the Comparative Toxicogenomics Database (CTD). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses and protein-protein interaction (PPI) network were applied for integrative analyses. The rat model and molecular docking were applied to furtherly verifying the findings of the integrative analyses. Besides the highly related genes, most enriched pathways and chemicals for hypospadias and cryptorchidism respectively, we found hypospadias and cryptorchidism share many same highly associated EDCs (e.g., dibutyl phthalate) and genes (e.g., androgen receptor and estrogen receptor 1) through comparing highly related chemicals or genes of hypospadias and cryptorchidism respectively. GO and KEGG analysis showed that these same interactive genes were mainly enriched in steroidogenesis, response to steroid hormone and nuclear receptor activity. PPI network analysis identified 15 biological hub genes. Furtherly, hypospadias and cryptorchidism were induced by prenatal dibutyl phthalate exposure. Decreased serum testosterone level, downregulation of nuclear androgen-dependent and upregulation of cytoplasmic estrogen-dependent pathways may lead to hypospadias and cryptorchidism. This study proposed a new method for predicting the correlation between the interactive genes of hypospadias/cryptorchidism and chemicals and found that hypospadias and cryptorchidism share many same highly associated EDCs and genes.

Abstract Background Considerable evidence has indicated an association between the immune microenvironment and clinical outcome in ccRCC. The purpose of this study is to extensively figure out the influence of immune-related genes of tumors on the prognosis of patients with ccRCC. Methods Files containing 2498 immune-related genes were obtained from the Immunology Database and Analysis Portal (ImmPort), and the transcriptome data and clinical information relevant to patients with ccRCC were identified and downloaded from the TCGA data-base. Univariate and multivariate Cox regression analyses were used to screen out prognostic immune genes. The immune risk score model was established in light of the regression coefficient between survival and hub immune-related genes. We eventually set up a nomogram for the prediction of the overall survival for ccRCC. Kaplan-Meier (K-M) and ROC curve was used in evaluating the value of the predictive risk model. A P value of

Blood-testis barrier (BTB) damage promotes spermatogenesis dysfunction, which is a critical cause of male infertility. Dyslipidemia has been correlated with male infertility, but the major hazardous lipid and the underlying mechanism remains unclear. In this study, we firstly discovered an elevation of palmitic acid (PA) and a decrease of inhibin B in patients with severe dyszoospermia, which leaded us to explore the effects of PA on Sertoli cells. We observed a damage of BTB by PA. PA penetration to endoplasmic reticulum (ER) and its damage to ER structures were exhibited by microimaging and dynamic observation, and consequent ER stress was proved to mediate PA-induced Sertoli cell barrier disruption. Remarkably, we demonstrated a critical role of aberrant protein palmitoylation in PA-induced Sertoli cell barrier dysfunction. An ER protein, Calnexin, was screened out and was demonstrated to participate in this process, and suppression of its palmitoylation showed an ameliorating effect. We also found that ω-3 poly-unsaturated fatty acids down-regulated Calnexin palmitoylation, and alleviated BTB dysfunction. Our results indicate that dysregulated palmitoylation induced by PA plays a pivotal role in BTB disruption and subsequent spermatogenesis dysfunction, suggesting that protein palmitoylation might be therapeutically targetable in male infertility.

BackgroundRenal clear cell cancer (ccRCC) is one of the most common cancers in humans. Thus, we aimed to construct a risk model to predict the prognosis of ccRCC effectively.MethodsWe downloaded RNA sequencing (RNA-seq) data and clinical information of 539 kidney renal clear cell carcinoma (KIRC) patients and 72 normal humans from The Cancer Genome Atlas (TCGA) database and divided the data into training and testing groups randomly. Pyroptosis-related lncRNAs (PRLs) were obtained through Pearson correlation between pyroptosis genes and all lncRNAs (p 0.3). Univariate and multivariate Cox regression analyses were then performed to select suitable lncRNAs. Next, a novel signature was constructed and evaluated by survival analysis and ROC analysis. The same observation applies to the testing group to validate the value of the signature. By gene set enrichment analysis (GSEA), we predicted the underlying signaling pathway. Furthermore, we calculated immune cell infiltration, immune checkpoint, the T-cell receptor/B-cell receptor (TCR/BCR), SNV, and Tumor Immune Dysfunction and Exclusion (TIDE) scores in TCGA database. We also validated our model with an immunotherapy cohort. Finally, the expression of PRLs was validated by quantitative PCR (qPCR).ResultsWe constructed a prognostic signature composed of six key lncRNAs (U62317.1, MIR193BHG, LINC02027, AC121338.2, AC005785.1, AC156455.1), which significantly predict different overall survival (OS) rates. The efficiency was demonstrated using the receiver operating characteristic (ROC) curve. The signature was observed to be an independent prognostic factor in cohorts. In addition, we found the PRLs promote the tumor progression via immune-related pathways revealed in GSEA. Furthermore, the TCR, BCR, and SNV data were retrieved to screen immune features, and immune cell scores were calculated to measure the effect of the immune microenvironment on the risk model, indicating that high- and low-risk scores have different immune statuses. The TIDE algorithm was then used to predict the immune checkpoint blockade (ICB) response of our model, and subclass mapping was used to verify our model in another immunotherapy cohort data. Finally, qPCR validates the PRLs in cell lines.ConclusionThis study provided a new risk model to evaluate ccRCC and may be pyroptosis-related therapeutic targets in the clinic.

BackgroundThe key regulatory roles of long non-coding RNAs (lncRNAs) in age-related erectile dysfunction (A-ED) are unknown.AimThis study aimed to identify putative lncRNAs that regulate age-related erectile dysfunction via transcriptome analyses, and to predict their specific regulatory routes via bioinformatics methods.Methods22 geriatric male SD rats were divided into age-related erectile dysfunction (A-ED) and negative control (NC) groups after evaluations of intracavernous pressure (ICP). By comparative analysis of transcriptomes of cavernosal tissues from both groups, we identified differentially expressed lncRNAs, miRNAs, and mRNAs. Seven differentially expressed lncRNAs were selected and further verified by quantitative real-time polymerase chain reactions (RT-qPCR). The construction of the lncRNA-miRNA-mRNA network, the Gene Ontology (GO) term enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in Cytoscape.ResultsFrom comparative transcriptome analyses of A-ED and NC groups, 69, 29, and 364 differentially expressed lncRNAs, miRNAs, and mRNAs were identified respectively. Differentially expressed lncRNAs were culled to seven, which were all verified by qPCR. Three of these lncRNAs (ENSRNOT00000090050, ENSRNOT00000076482, and ENSRNOT00000029245) were used to build regulatory networks, of which only ENSRNOT00000029245 was successful. Moreover, GO and KEGG analyses demonstrated that these lncRNAs possibly regulated muscle myosin complex, muscle cell cellular homeostasis, and ultimately erectile function in rats through PI3K-Akt, fluid shear stress, and atherosclerosis pathways.ConclusionOur study identified differentially expressed lncRNAs, miRNAs, and mRNAs through comparisons of transcriptomes of geriatric rats. An identified lncRNA verified by qPCR, was used to construct a lncRNA-miRNA-mRNA regulatory network. LncRNA ENSRNOT00000029245 possibly regulated downstream mRNAs through this regulatory network, leading to apoptosis in the cavernous tissue, fibrosis, and endothelial dysfunction, which ultimately caused ED. These findings provide seminal insights into the molecular biology of aging-related ED, which could spur the development of effective therapeutics.

Sertoli cell-only syndrome (SCOS) is the most severe and common pathological type of non-obstructive azoospermia. The etiology of SCOS remains largely unknown to date despite a handful of studies reported in this area. According to the gene expression of testicular tissue samples in six datasets from the Gene Expression Omnibus, we detected 1441 differentially expressed genes (DEGs) between SCOS and obstructive azoospermia (OA) testicular tissue samples. Enriched GO terms and KEGG pathways for the downregulated genes included various terms and pathways related to cell cycle and reproduction, while the enrichment for the upregulated genes yielded many inflammation-related terms and pathways. In accordance with the protein-protein interaction (PPI) network, all genes in the most critical module belonged to the downregulated DEGs, and we obtained nine hub genes, including CCNB1, AURKA, CCNA2, BIRC5, TYMS, UBE2C, CDC20, TOP2A, and OIP5. Among these hub genes, six were also found in the most significant SCOS-specific module obtained from consensus module analysis. In addition, most of SCOS-specific modules did not have a consensus counterpart. Based on the downregulated genes, transcription factors (TFs) and kinases within the upstream regulatory network were predicted. Then, we compared the difference in infiltrating levels of immune cells between OA and SCOS samples and found a significantly higher degree of infiltration for most immune cells in SCOS than OA samples. Moreover, CD56bright natural killer cell was significantly associated with six hub genes. Enriched hallmark pathways in SCOS had remarkably more upregulated pathways than the downregulated ones. Collectively, we detected DEGs, significant modules, hub genes, upstream TFs and kinases, enriched downstream pathways, and infiltrated immune cells that might be specifically implicated in the pathogenesis of SCOS. These findings provide new insights into the pathogenesis of SCOS and fuel future advances in its theranostics.

BackgroundAdipogenic transdifferentiation was an important carcinogenic factor in various tumors, while studies on its role in clear cell renal cell carcinoma (ccRCC) were still relatively few. This study aimed to investigate its prognostic value and mechanism of action in ccRCC.MethodsGene expression profiles and clinical data of ccRCC patients were obtained from The Cancer Genome Atlas database. Nonnegative matrix factorization was used for clustering. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were used to analyze the pathways and biological process activities. single-sample GSEA (ssGSEA) was utilized to quantify the relative abundance of each immune cell. Tumor Immune Estimation Resource (TIMER) was used to evaluate the proportion of various immune infiltrating cells across diverse cancer types. Real-Time PCR was performed to examine the gene expression. R software was utilized to analyze the expression and prognostic role of genes in ccRCC.ResultsA total of 49 adipose-related genes (ARGs) were screened for differential expression between normal and ccRCC tissues. Based on differentially expressed ARGs, patients with ccRCC were divided into two adipose subtypes with different clinical, molecular, and pathway characteristics. Patients in cluster A exhibited more advanced pathological stages, higher expressions of RARRES2 and immune checkpoint genes, higher immune infiltration scores, and less nutrient metabolism pathways. Adipose differentiation index (ADI) was constructed according to the above ARGs and survival data, and its robustness and accuracy was validated in different cohorts. In addition, it was found that the expression of ARGs was associated with immune cell infiltration and immune checkpoint in ccRCC, among which GBP2 was thought to be the most relevant gene to the tumor immune microenvironment and play a potential role in carcinogenesis and invasion of tumor cells.ConclusionOur analysis revealed the consistency of higher adipogenic transdifferentiation of tumor cells with worse clinical outcomes in ccRCC. The 16-mRNA signature could predict the prognosis of ccRCC patients with high accuracy. ARGs such as GBP2 might shed light on the development of novel biomarkers and immunotherapies of ccRCC.

BackgroundIt is well known that chronic inflammation can promote the occurrence and progression of cancer. As a type of proinflammatory death, pyroptosis can recast a suitable microenvironment to promote tumor growth. However, the potential role of pyroptosis in clear cell renal cell carcinoma (ccRCC) remains unclear.MethodsThe transcriptome expression profile and mutation profile data of ccRCC with clinical characteristics included in this study were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Consensus clustering was used for clustering. Gene set enrichment analysis (GSEA) analysis were applied to evaluate the biological mechanisms. Single sample gene set enrichment analysis (ssGSEA) was applied for evaluating the proportion of various immune infiltrating cells. The ESTIMATE algorithm was involved to compute the immune microenvironment scores.ResultsAmong the 17 pyroptosis regulators, a total of 15 pyroptosis regulators were differential expressed between tumor and normal tissues, in which 12 of them emerged strong correlations with prognoses. According to the pyroptosis components, the ccRCC patients were divided into four pyroptosis subtypes with different clinical, molecular, and pathway characteristics. Compared with other clusters, cluster B showed the pyroptosis heat phenotype, while cluster D represented the pyroptosis cold phenotype with poor overall survival. In addition, we performed principal component analysis (PCA) on the differential genes between clusters to construct the pyroptosis index. Furthermore, the pyroptosis index was significantly correlated with survival in different tumor mutation statuses and different grades and stages. Besides, the expression of pyroptosis-related regulators was related to the infiltration of immune cells and the expression of immune checkpoints, among which AIM2 was considered as the most significant immune-related pyroptosis regulator. Ultimately, we found that AIM2 was related to the immune activation pathway and was significantly overexpressed in tumor tissues.ConclusionThis study revealed that pyroptosis regulators and pyroptosis index played an important role in the development and prognoses of ccRCC. Moreover, AIM2 can be used as a predictor of the response of immunotherapy. Assessing the pyroptosis patterns may help evaluate the tumor status and guide immunotherapy strategies.

Background: Long non-coding RNAs (lncRNAs) are now under discussion as novel promising biomarkers for clear cell renal cell carcinoma (ccRCC). However, the role of genomic instability-associated lncRNA signatures in tumors has not been thoroughly uncovered. The purpose of our study is to probe the role of genomic instability-derived lncRNA signature (GILncSig) and to further investigate the mechanism of genomic instability-mediated ccRCC progression.Methods: The transcriptome data and somatic mutation profiles of ccRCC as well as clinical characteristics used in this study were obtained from The Cancer Genome Atlas database and Gene Expression Omnibus database. Lasso regression analysis was performed to construct the GILncSig. Gene set enrichment analysis (GSEA) was performed to elucidate the biological functions and relative pathways. CIBERSORT and EPIC algorithm were applied to calculate the proportion of immune cells in ccRCC. ESTIMATE algorithm was utilized to compute the immune microenvironment scores.Results: In total, 148 novel genomic instability-derived lncRNAs in ccRCC were identified. Immediately, on the basis of univariate cox analysis and lasso analysis, a GILncSig was appraised, through which the patients were allocated into High-Risk and Low-Risk groups with significantly different characteristics and prognoses. In addition, we confirmed that the somatic mutation count, tumor mutation burden, and the expression of UBQLN4, which were ascertainably associated with genomic instability, were significantly correlated with the GILncSig, indicating its reliability as a measurement of the genomic instability. Furthermore, the efficiency of GILncSig in prognostic aspects was better than the single mutation gene in ccRCC. In addition, MNX1-AS1 was defined to be a potential biomarker characterized by strong correlation with clinical features. Moreover, GSEA results indicated that the IL6/JAK/STAT3/SIGNALING pathway could be considered as a potential mechanism of genomic instability to influence tumor progression. Besides, the immune microenvironment showed significant differences between the GS-like group and the GU-like group, which was specifically manifested as high expression of CTLA4, GITR, TNFSF14, and regulatory T cells (Tregs) as well as low expression of endothelial cells (ECs) in the GU-like group. Finally, the prognostic value and clinical relevance of GILncSig were verified in GEO datasets and other urinary tumors in TCGA dataset.Conclusion: In conclusion, our study provided a new perspective for the role of lncRNAs in genomic instability and revealed that genomic instability may mediate tumor progression by affecting immunity. Besides, MNX1-AS1 played critical roles in promoting the progression of ccRCC, which may be a potential therapeutic target. What is more, the immune atlas of genomic instability was characterized by high expression of CTLA4, GITR, TNFSF14, and Tregs, and low expression of ECs.

Di-n-butyl phthalate (DBP) is a widely used plasticizer and an environmental endocrine-disrupting compound. However, whether prenatal exposure to DBP can impair erectile function remains unknown. We conducted this study to investigate the potential effects of prenatal exposure to DBP on erectile function and the underlying mechanisms. A rat model of prenatal DBP exposure (12.5, 100 or 800 mg/kg/day by gavage during gestational days 13–21) was established. Prenatal DBP exposure significantly decreased penis/body weight ratio, myelin sheath thickness of cavernosum nerves and serum testosterone level in male rats at the age of 10 weeks. Furthermore, erectile dysfunction was detected in all DBP exposure groups, which exhibited substantial increases in transforming growth factor-β1 (TGF-β1) expression and decreases in the expression of alpha smooth muscle actin (α-SMA), neuronal and endothelial nitric oxide synthase (nNOS and eNOS). Additionally, the phospho-B-cell lymphoma 2 (Bcl-2)-associated death promoter (p-Bad)/Bad and phospho-the protein kinase B (p-AKT)/AKT ratios were remarkably lower, but the Bcl-2-associated X protein (Bax)/Bcl-2 ratio and caspase-3 were higher in DBP exposure groups than in the control group. Notably, prenatal exposure to DBP increase the risk of ED in male adult rats, even taking low dose of DBP (12.5 mg/kg/day). DBP exposure causing penile fibrosis, decreased testosterone level, and endothelial dysfunction may be responsible for ED by activating Akt/Bad/Bax/caspase-3 pathway and suppressing NOS/cGMP pathway in penis.

Abstract Background The mammalian homologs of Lin-28, Lin28 (also called Lin28A) and Lin28B, are promising cancer biomarkers. This meta-analysis was performed to evaluate the prognostic values of Lin28A and Lin28B in multiple human malignancies. Methods Systematic searches of the PubMed, Web of Science and Embase were used to identify relevant studies. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), or progression-free survival (PFS) were respectively calculated. Results 3772 Lin28A-associated patients and 1730 Lin28B-related cases were ultimately enrolled in this meta-analysis. The elevated expression level of Lin28A was significantly associated with poor OS (HR = 1.60, P

Abstract Background To investigate the potential prognostic role of pre-treatment prognostic nutritional index (PNI) in urinary cancers. Methods Relevant articles were searched comprehensively from PubMed, Embase and Web of Science, up to November 2018. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to evaluate their associations. Result A total of 12 related articles including 6561 patients were ultimately enrolled. Our results indicated that a relatively lower level of pre-treatment PNI was associated with decreased OS, CSS/DSS and DFS/RFS/PFS (pooled HR = 1.68, 95% CI 1.45–1.95; pooled HR = 1.57, 95% CI 1.33–1.86; pooled HR = 1.75, 95% CI 1.53–1.99, respectively). Subsequent stratified analysis by cancer type for OS showed that PNI could also be a predictor no matter in renal cell cancer (RCC) or bladder cancer (BC) (pooled HR = 1.65, 95% CI 1.37–1.97 and pooled HR = 1.67, 95% CI 1.20–2.33). Similar results could be found in DFS/RFS/PFS (RCC: HR = 1.81, 95% CI 1.54–2.13 and BC: HR = 1.68, 95% CI 1.32–2.12) and in CSS/DSS (RCC: HR = 1.50, 95% CI 1.23–1.82 and upper tract urothelial carcinoma: HR = 1.61, 95% CI 1.13–2.28). As for the treatment subgroup, a relatively lower level of PNI could also be a positive predictor for OS (surgery: HR = 1.64, 95% CI 1.40–1.93; target therapy: HR = 1.88, 95% CI 1.34–2.63) and DFS/RFS/PFS (surgery: HR = 1.69, 95% CI 1.47–1.95; target therapy: HR = 2.14, 95% CI 1.50–3.05). Conclusion The outcomes of us shed light on that elevated pre-treatment PNI was positively associated with OS, CSS/DSS and DFS/RFS/PFS, indicating that it could be an independent prognostic factor in urinary cancers.

Abstract Background Although accumulating data have suggested the development of cancer in systemic lupus erythematosus (SLE) patients, these results remain inconsistent. To examine such a putative association, this analysis reports the association between SLE and the risks of 24 cancer types. Methods Online databases PubMed, EMBASE, and Web of Science were searched comprehensively for eligible studies, published up to 15 May 2018. Pooled standardized incidence rates (SIRs) with 95% confidence intervals (CIs) were utilized to reveal their associations. Results A total of 24 eligible studies were ultimately enrolled. Our results indicated that SLE was associated with increased risk of overall cancers, cancer risk in both genders, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, leukemia, multiple myeloma, cervix, vagina/vulva, renal, bladder, esophagus, gastric, hepatobiliary, lung, oropharynx, larynx, non-melanoma skin, and thyroid cancers. Additionally, SLE could reduce the risk of prostate cancer and cutaneous melanoma; however, it was not significantly associated with breast, uterus, ovarian, pancreatic, colorectal, or brain cancers. Conclusions Our results shed light SLE being correlated with increased risk for 16 involved cancers and decreased risk for prostate cancer and cutaneous melanoma. This comprehensive meta-analysis provides epidemiological evidence supporting the associations between SLE and cancer risk. This evidence could be utilized to drive public policies and to help guide personalized medicine to better manage SLE and reduce associated cancer morbidity and mortality.

Testicular germ cell tumors (TGCTs) are common urological neoplasms in young adult males. The outcome of TGCT depends on pathologic type and tumor stage. RNA-binding proteins (RBPs) influence numerous cancers via post-transcriptional regulation. The prognostic importance of RBPs in TGCT has not been fully investigated. In this study, we set up a prognostic risk model of TGCT using six significantly differentially expressed RBPs, namely, TRMT61A, POLR2J, DIS3L2, IFIH1, IGHMBP2, and NPM2. The expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression datasets. We observed by performing least absolute shrinkage and selection operator (LASSO) regression analyses that in the training cohort, the expression of six RBPs was correlated with disease-free survival in patients with TGCT. We assessed the specificity and sensitivity of 1-, 3-, 5-, and 10-year survival status prediction using receiver operating characteristic curve analysis and successfully validated using the test cohorts, the entire TCGA cohort, and Gene Expression Omnibus (GEO) datasets. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses were carried out to seek the possible signaling pathways related with risk score. We also examined the association between the model based on six RBPs and different clinical characteristics. A nomogram was established for TGCT recurrence prediction. Consensus clustering analysis was carried out to identify the clusters of TGCT with different clinical outcomes. Ultimately, external validations of the six-gene risk score were performed by using the GSE3218 and GSE10783 datasets downloaded from the GEO database. In general, our study constructed a prognostic model based on six RBPs, which could serve as independent risk factor in TGCT, especially in seminoma, and might have brilliant clinical application value.

Extensive research has revealed that the score derived from the Gleason grading system plays a pivotal role in predicting prostate cancer (PCa) progression. However, the underlying involvement of Gleason-related genes in PCa requires further investigation. This study aimed to identify Gleason-related genes with the potential to guide PCa therapy and future research. Differentially expressed genes (DEGs) were identified by comparing PCa tissues with high or low Gleason scores using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. R v3.6.1, SPSS v23, and ImageJ software were used for all analyses. An effective recurrence-free survival (RFS) predictive model based on seven Gleason-related genes was established and validated (TCGA, AUC = 0.803; five years, AUC = 0.740; three years, AUC = 0.722; one year, AUC = 0.711; GSE46602, AUC = 0.766; five years, AUC = 0.808; three years, AUC = 0.723; one year, AUC = 0.656; GSE116918, AUC = 0.788; five years, AUC = 0.704; three years, AUC = 0.693; one year, AUC = 0.996). Calibration and nomogram plots were conducted. Weighted correlation network analysis (WGCNA) was used, and COL5A2 was selected for further analysis. The results from in vitro experiments demonstrated that COL5A2 was upregulated in PCa with high Gleason scores. The knockdown of COL5A2 inhibited cell proliferation and invasion in PC-3 and LNCaP cell lines. Meanwhile, COL5A2 displayed a strong association with immune infiltration, which might be an underlying immunotherapy target for PCa. We successfully established a robust RFS predictive model. The findings from this study indicated that COL5A2 could promote cell proliferation and invasion in PCa.

Background: Nowadays, predictions of biochemical recurrence (BCR) in localized prostate cancer (PCa) patients after radical prostatectomy (RP) are mainly based on clinical parameters with a low predictive accuracy. Given the critical role of apoptosis in PCa occurrence and progression, we aimed to establish a novel predictive model based on apoptosis-related gene signature and clinicopathological parameters that can improve risk stratification for BCR and assist in clinical decision-making.Methods: Expression data and corresponding clinical information were obtained from four public cohorts, one from The Cancer Genome Atlas (TCGA) dataset and three from the Gene Expression Omnibus (GEO) dataset. Weighted gene co-expression network analysis (WGCNA) was performed to identify candidate modules closely correlated to BCR, and univariate and multivariate Cox regression analyses were utilized to build the gene signature. Time-dependent receiver operating curve (ROC) and Kaplan–Meier (KM) survival analysis were used to assess the prognostic value. Finally, we analyzed the expression of genes in the signature and validated the results using quantitative real-time PCR (qRT-PCR).Results: The novel gene signature we established exhibited a high prognostic value and was able to act as an independent risk factor for BCR [Training set: P < 0.001, hazard ratio (HR) = 7.826; Validation set I: P = 0.006, HR = 2.655; Validation set II: P = 0.003, HR = 4.175; Validation set III: P < 0.001, HR = 3.008]. Nomogram based on the gene signature and clinical parameters was capable of distinguishing high-risk BCR patients. Additionally, functional enrichment analysis showed several enriched pathways and biological processes, which might help reveal the underlying mechanism. The expression results of qRT-PCR were consistent with TCGA results.Conclusion: The apoptosis-related gene signature could serve as a powerful predictor and risk factor for BCR in localized PCa patients after RP.

Abstract Background Galectin-3 as a β-galactoside-binding protein, has been found to be involved in tumor cell growth, anti-apoptosis, adhesion, angiogenesis, invasion, and distant metastases, indicating that it may play a pivotal role in cancer development and progression. However, their results remain debatable and inconclusive. Hence, this meta-analysis was performed to clarify the precise predictive value of galectin-3 in various cancers. Methods PubMed, Web of Science, Embase, Cochrane Library, CNKI and Wanfang databases were searched comprehensively for eligible studies up to July 15, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of OS or DFS/PFS/RFS were calculated to demonstrate their associations. Results A total of 36 relevant studies were ultimately enrolled in this meta-analysis. Our results shed light on the significant association of elevated galectin-3 expression with reduced OS or DFS/RFS/PFS in overall cancer patients (pooled HR = 1.79, 95% CI 1.42–2.27, I 2= 67.3%, p

Background/Aims: Urothelial cancer (UC) as a chemotherapy-sensitive tumor, has achieved remarkable progresses in therapeutic paradigm, particularly in the advanced/metastatic stages. However, both clinicians and patients are confused when it comes to choosing the optimal chemotherapy. Hence, this article was aimed to conduct a comprehensive comparison of different chemotherapy regimens for advanced or metastatic UC in terms of survival benefits or adverse events. Methods: The online databases PubMed, EMBASE and Web of Science were searched systematically and comprehensively for randomized controlled trials (RCTs) up to September 15, 2017. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% credible interval (CrI) were calculated by Markov chain Monte Carlo methods. The effectiveness and safety of included regimens were conducted to provide a hierarchy by means of rank probabilities with the help of “R-3.4.0” software and the “gemtc-0.8.2” package. The surface under the cumulative ranking curve (SUCRA) was also incorporated in our analysis for ranking the corresponding chemotherapy regimens. Results: Ten different chemotherapy regimens involved in this article were predominantly of trials in a first-line setting, and eight clinical outcomes were ultimately analyzed in this study. In terms of Overall response rate (ORR), Overall survival (OS) or Progression-free survival (PFS)/Time to progression (TTP), the rank probabilities and SUCRA indicated that Paclitaxel/cisplatin/gemcitabine (PCG) was superior to gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), the traditional first-line treatment for advanced/metastatic UC. In the case of ORR or PFS/TTP, GC+sorafenib also displayed its superiority in comparison with GC or MVAC. Despite their survival benefits, PCG or GC+sorafenib presented a relatively higher incidence of adverse events. Conclusion: Our results revealed that by adding a paclitaxel or sorafenib into the first-line GC, it could yield a better survival benefit, but also worsen adverse events for advanced/ metastatic UC. Clinically, physicians should weigh the merits of these approaches to maximize the survival benefits of eligible patients.

Abstract Background To assess the safety and efficacy of laparoscopic retroperitoneal resection for retroperitoneal lymphatic cysts. Methods A retrospective analysis was conducted based on clinical data from eight patients with hydronephrosis caused by retroperitoneal lymphatic cysts. All patients underwent laparoscopic retroperitoneal lymphatic cyst resection and received postoperative follow-up. A follow-up ultrasound was performed postoperatively every 6–12 months to evaluate the recovery of the hydronephrosis. Results All operations were successful, and their postoperative pathological results revealed lymphatic cyst walls. The operation time ranged from 43 to 88 min (mean: 62 min), with a blood loss of 20 to 130 mL (mean: 76 mL), and the length of hospital stay was 3 to 6 days (mean: 4.5 days). Within the follow-up of 12 to 36 months (mean: 28.5 months), great relief was detected in all eight cases, and no recurrence was found. Moreover, complications such as renal pedicle or renal pelvis injury were not observed. Conclusions Laparoscopic retroperitoneal lymphatic cyst resection is an effective treatment for retroperitoneal lymphatic cysts and has the advantages of being minimally invasive, producing less intraoperative blood loss and leading to a quick recovery. This treatment thus deserves further studies.

Background: Voltage-dependent anion channel (VDAC), a channel protein, exists in the outer mitochondrial membrane of somatic cells and is involved in multiple physiological and pathophysiological processes. Up until now, little has been known about VDAC in male germ cells. In the present study, the relationship between VDAC and human sperm motility was explored. Methods: Highly motile human spermatozoa were incubated in vitro with anti-VDAC antibody. Total sperm motility, straight line velocity (VSL), curvilinear velocity (VCL), and average path velocity (VAP) were recorded. Intracellular free calcium concentration ([Ca2+]i), pH value (pHi), and ATP content were determined. Results: Co-incubation with anti-VDAC antibody reduced VSL, VCL, and VAP of spermatozoa. Co-incubation further reduced [Ca2+]i. Anti-VDAC antibody did not significantly alter total sperm motility, pHi and intracellular ATP content. Conclusion: The data suggest that co-incubation with anti-VDAC antibody reduces sperm motility through inhibition of Ca2+ transmembrane flow. In this way, VDAC participates in the modulation of human sperm motility through mediating Ca2+ transmembrane transport and exchange.

Background: Clusterin, a heterodimeric glycoprotein of approximately 80 kDa, exists extensively in human body fluids. The abnormal expression of clusterin is closely related to the occurrence, progression, and prognosis of tumors. Up to now, few studies have focused on clusterin in human testicular cancer. This study describes an extensive exploration of the presence and expression of clusterin in testicular seminoma. Methods: Tumor tissues and normal testis tissues were collected from 13 patients with testicular seminoma and 16 patients undergoing surgical castration for prostate cancer. Real-time polymerase chain reaction (PCR) was performed to detect the expression difference of clusterin mRNA between testicular seminoma and normal testis. Western blot and immunohistochemical analysis were performed to detect the presence and expression difference of clusterin protein between two groups. Results: Real-time PCR showed the expression of clusterin mRNA in testicular seminoma to be significantly lower than in normal testis (only 13% relative quantification). Western blot analysis indicated marked reductions in the expression of clusterin protein in testicular seminoma. Similar results were observed upon immunohistochemical analysis. Conclusion: In testicular seminoma and normal testis, clusterin exists in its heterodimeric secretory isoform. Clusterin expression is significantly lower in testicular seminoma than in normal testis. This is the first comprehensive study of the presence and expression of clusterin in human testicular cancer.