Associations of waist circumference with sex steroid hormones among 4031 USA children and adolescents.

In the recent decades, obesity rates among children and adolescents, especially males, have increased significantly. This worldwide phenomenon is thought to significantly affect the levels of sex hormones. However, the association between waist circumference (a marker of abdominal obesity) and sex hormone levels in children and adolescents is unknown. In this study, 4031 participants aged 6-19 years from the United States National Health and Nutrition Examination Survey (NHANES) in the USA were enrolled in this study. The common confounders of age, race, body mass index, educational level, family income, diabetes, and time of sample collection were also collected. The participants missing any of the above information were excluded from the study. We used multiple linear regression and other multiple statistics to assess the associations between waist circumference and serum testosterone, estradiol, sex hormone-binding globulin (SHBG), free androgen index (FAI), and testosterone/estradiol ratio (T/E2). Waist circumference remained associated with sex hormone levels in children and adolescents after controlling for covariates. As waist circumference increases, testosterone levels in children and adolescents show an overall decline after a brief increase, with the inflection point for waist circumference of 65-66 cm. In addition, waist circumference positively correlates with estradiol levels in male children (ß = 0.007, 95% confidence interval: 0.004-0.009). Moreover, circulating SHBG decreases in children and adolescents as waist circumference increases. In conclusion, this study highlighted waist circumference as a vital indicator affecting sex hormone levels in children and adolescents.

Association of urinary phthalate metabolites with renal function among 9989 US adults.

PURPOSE: This study aimed to investigate the relationship between phthalate metabolites and renal function. METHODS: We analyzed data from 9989 participants who took part in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Renal function was reflected by estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and hypertension. We used generalized linear regression to estimate the correlation between covariate-adjusted creatinine-normalized phthalate metabolites and renal function. In addition, subgroup analysis was used to further compare the effect differences between various populations. RESULTS: In the adjusted model, we found differential associations between phthalates and plasticizers metabolites and renal function. We found that Mono-benzyl phthalate, Mono-(3-carboxypropyl) phthalate, and Mono-(2-ethyl-5-oxohexyl) phthalate were positively associated with lower eGFR with odds ratios (95% confidence intervals) of 1.38 (1.14, 1.67), 1.30 (1.09, 1.57), and 1.27 (1.04, 1.53). While Mono-ethyl phthalate, Mono-(2-ethyl)-hexyl phthalate, Mono-isononyl phthalate and Mono-isobutyl phthalate were negatively associated with lower eGFR with OR values of 0.79 (0.69, 0.90), 0.64 (0.52, 0.78), 0.65 (0.51, 0.82) and 0.80 (0.63, 1.00), respectively. In addition, we found that Mono(carboxyoctyl) phthalate and Mono-isobutyl phthalate were negatively associated with hypertension with ORs of 0.86 (0.78, 0.96) and 0.84 (0.72, 0.98). But phthalates and plasticizers metabolites were not associated with UACR. CONCLUSION: This study found differences in the effects of phthalates and plasticizers metabolites on kidney function, which may raise concerns about possible changes in kidney function resulting from exposure to current levels of plasticizers.

Survival Prognosis, Tumor Immune Landscape, and Immune Responses of ADAMTS14 in Clear Cell Renal Cell Carcinoma and Its Potential Mechanisms.

Background: ADAMTS14 played a crucial role in the formation and development of various cancers. Currently, no associations had been revealed between ADAMTS14 and clear cell renal cell carcinoma (ccRCC). Hence, this study was designed to assess the prognostic values and immunological roles of ADAMTS14 in ccRCC and to reveal its potential mechanisms. Methods: ADAMTS14-related expression profiles and related clinical data were downloaded from The Cancer Genome Atlas (TCGA) dataset, validated by the ICGC dataset, qRT-PCR, and immunohistochemistry. We utilized gene set enrichment analysis (GSEA) to find potentially ADAMTS14-related pathways and applied univariate/multivariate Cox regression analyses to identify independent factors significantly related to overall survival (OS) for ccRCC. A nomogram consisted of independent prognostic factors was also conducted. We further explored the associations between ADAMTS14 with immunity and revealed its potential mechanisms. Results: ADAMTS14 displayed a higher expression in ccRCC tumor than in adjacent normal tissues, and further validated results of the ICGC dataset; qRT-PCR and immunohistochemistry remained consistent (all p < 0.05). Moreover, elevated ADAMTS14 expression was significantly associated with poor OS (p < 0.001). Through univariate/multivariate Cox regression analyses, ADAMTS14 was found to be an independent prognostic factor for ccRCC (both p < 0.05) and GSEA identified several signaling pathways including INSULIN, MTOR, and PPAR pathways. The nomogram based on independent prognostic factors was successfully established and well evaluated. Moreover, the expression of ADAMTS14 was remarkably associated with immune checkpoint molecules, tumor mutational burden (TMB), immune cells, and tumor immune microenvironment (all p < 0.05). Results from TIDE and TCIA showed that highly expressed ADAMTS14 could predict worse efficacy of immunotherapy (all p < 0.05). As for its potential mechanisms, we also revealed several LncRNA/RNA binding protein (RBP)/ADAMTS14 mRNA networks. Conclusions: ADAMTS14 was found to play oncogenic roles in ccRCC and to be significantly associated with immunity. Several LncRNA/RBP/ADAMTS14 mRNA networks were also identified for its potential mechanisms.

Survival Prognosis, Tumor Immune Landscape, and Immune Responses of PPP1R18 in Kidney Renal Clear Cell Carcinoma and Its Potentially Double Mechanisms.

Background: The aim of this study was to investigate the immunological and prognostic roles of protein phosphatase 1 regulatory subunit 18 (PPP1R18) for overall survival (OS) in kidney renal clear cell carcinoma (KIRC) patients, as well as the prediction of its potential mechanisms. Methods: Based on PPP1R18 single gene expression matrices and clinical information from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and GSE6344 datasets, the relationships between PPP1R18 and prognosis/immunity were fully explored. Univariate and multivariate Cox regression analyses were applied to assess its independent prognostic ability and gene set enrichment analysis (GSEA) was implemented to find its related pathways. Besides, we also explored possible mechanisms of PPP1R18 involved in KIRC. Results: PPP1R18 was highly expressed in KIRC samples than in non-tumor tissues in TCGA, ICGC and GSE6344 datasets, with validations from quantitative real-time polymerase chain reaction (qRT-PCR) in both cell lines and KIRC tissues (all P < 0.05). Univariate and multivariate Cox regression analyses indicated that PPP1R18 was also considered to be with independent prognostic ability in KIRC (both P < 0.01). GSEA results showed that PPP1R18 gene expression was significantly related to Chemokine, JAK STAT, MAPK, and NOTCH pathways. Furthermore, PPP1R18 was also firmly associated with microsatellite instability (MSI), tumor mutational burden (TMB), immune microenvironment, immune cells, immune checkpoints and immune infiltration (all P < 0.05). Analysis of tumor immune dysfunction and exclusion (TIDE) and Imvigor210 datasets suggested that patients with low PPP1R18 expression are more likely to benefit from immunotherapy. Finally, we identified two potential mechanisms of a classical competing endogenous RNA (ceRNA) mechanism and an RNA-binding protein (RBP) involved mechanism of PPP1R18 in KIRC. Conclusions: PPP1R18 played oncogenic and immunological roles of OS in KIRC, offering potential antigens for developing KIRC mRNA vaccines.

Clusterin suppresses invasion and metastasis of testicular seminoma by upregulating COL15a1.

Seminoma is the most common subtype of testicular germ cell tumor, with an increasing incidence worldwide. Clusterin (CLU) expression was found to be downregulated in testicular seminoma in our previous study. We now expanded the sample size, and further indicated that CLU expression correlates with tumor stage. Tcam-2 cell line was used to investigate the CLU function in testicular seminoma, and CLU was found to inhibit the proliferation and metastasis abilities. Besides, extracellular matrix protein COL15a1 was demonstrated as the downstream of CLU to affect the epithelial-mesenchymal transition (EMT) process via competitively binding to DDR1 with COL1A1 and inhibiting the phosphorylation of PYK2. MEF2A was found to interact with CLU and bind to the promoter of COL15a1 and so upregulate its expression. This is the first study using testicular xenografts in situ to simulate testicular seminoma metastatic and proliferative capacities. In conclusion, CLU acts as a tumor suppressor to inhibit the metastasis of testicular seminoma by interacting with MEF2A to upregulate COL15a1 and blocking the EMT process.

Prognostic value and immunological role of AXL gene in clear cell renal cell carcinoma associated with identifying LncRNA/RBP/AXL mRNA networks.

BACKGROUNDS: This article aimed to explore the prognostic and immunological roles of AXL gene in clear cell renal cell carcinoma (ccRCC) for overall survival (OS) and to identify the LncRNA/RBP/AXL mRNA networks. METHODS: AXL-related gene expression matrix and clinical data were obtained from The Cancer Genome Atlas (TCGA) dataset and AXL-related pathways were identified by gene set enrichment analysis (GSEA). We performed univariate/multivariate Cox regression analysis to evaluate independent prognostic factors and the relationships between AXL and immunity were also investigated. RESULTS: The outcomes of us indicated that the AXL mRNA expression was up-regulated in ccRCC samples and high expression of AXL was associated with worse OS in TCGA dataset (P < 0.01). Further external verification results from HPA, UALCAN, ICGC dataset, GSE6344, GSE14994, and qRT-PCR remained consistent (all P < 0.05). AXL was also identified as an independent prognostic factor for ccRCC by univariate/multivariate Cox regression analysis (both P < 0.05). A nomogram including AXL expression and clinicopathological factors was established by us and GSEA results found that elevated AXL expression was associated with the JAK-STAT, P53, WNT, VEGF and MAPK signaling pathways. In terms of immunity, AXL was dramatically linked to tumor microenvironment, immune cells, immune infiltration, immune checkpoint molecules and tumor mutational burden (TMB). As for its potential mechanisms, we also identified several LncRNA/RBP/AXL mRNA axes. CONCLUSIONS: AXL was revealed to play prognostic and immunological roles in ccRCC and LncRNA/RBP/AXL mRNA axes were also identified by us for its potential mechanisms.

A novel 13 RNA binding proteins (RBPs) signature could predict prostate cancer biochemical recurrence.

BACKGROUND: Cancer precision medicine requires biomarkers or signatures to predict prognosis and therapeutic benefits. Driven by this, we established a biochemical recurrence (BCR) predictive model for prostate cancer (PCA) patients based on RNA-binding proteins (RBPs). METHODS: RNA-sequencing and corresponding clinicopathological data were downloaded from the Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. Univariate COX, LASSO and multivariate COX regression analyses were carried out to develop the BCR predictive riskScore model. Survival analysis, ROC curve, independent prognostic analysis, nomogram were also performed to evaluate this signature internally and externally. RESULTS: A total of 13 RBPs including TRMT1L, WBP4, MBNL3, SMAD9, NSUN7, ENG9, PIWIL4, PEG10, CSDC2, HELZ2, CELF2, YBX2 and ESRP2 were eventually identified as BCR-related hub biomarkers and utilized to establish a riskScore. Further analysis including external and internal verification indicated that the patients with high riskScores had shorter time to BCR compared to those with low riskScores in both TCGA and GSE116918. The area under the curve (AUC) of the time-dependent receiver operator characteristic curve (ROC) of the predictive model exhibited a good predictive performance. The signature was also proven to be a valuable independent prognostic factor (all P < 0.05). We also established a nomogram based on the 13 RBPs to visualize the relationships between individual predictors and 1-, 3- and 5-year BCR for PCA. CONCLUSIONS: Our results successfully screened out 13 RBPs as a robust BCR-predictive signature in PCA by external and internal verification, helping clinician predict patients' cancer progression status and promoting the specific individualized treatment than original clinical parameters.

Nucleolar protein NOP2 could serve as a potential prognostic predictor for clear cell renal cell carcinoma.

As an indispensable part for cancer precision medicine, biomarkers and signatures for predicting cancer prognosis and therapeutic benefits were urgently required. The purpose of this study was to investigate the prognostic roles of NOP2 in renal clear cell carcinoma (ccRCC) for overall survival (OS) and its relationships with immunity. NOP2-related gene expression matrix associated with clinical information was obtained from the Cancer Genome Atlas (TCGA) ccRCC dataset and NOP2-related pathways were identified by gene set enrichment analysis (GSEA). Associations among the NOP2 expression and MSI, TMB, TNB, and immunity were also explored. Both the NOP2 mRNA and protein/phosphoprotein had a higher expression in ccRCC tumor tissues than in normal kidney tissues (both P < 0.001) and elevated NOP2 expression was associated with poor OS (P < 0.001). Logistic regression analysis revealed the NOP2 expression was significantly linked to stage, age, grade, N stage, T stage, and M stage (all P < 0.05). Univariate/multivariate Cox hazard regression analysis results indicated that NOP2 was an independent prognostic factor for OS in ccRCC and GSEA revealed five NOP2-related signaling pathways. Nomogram based on NOP2 and eight clinical characteristic parameters (grade, age, stage, gender, T stage, race, M stage, N stage) was constructed and carefully evaluated. Furthermore, NOP2 gene expression was also found to be significantly related to MSI, TMB, and immunity. Our findings revealed that NOP2 might be a potential prognostic factor for OS in ccRCC and it was significantly associated with immunity, MSI, and TMB.

A novel 10 glycolysis-related genes signature could predict overall survival for clear cell renal cell carcinoma.

BACKGROUND: The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysis-related genes (GRGs) have been proven to be associated with tumor metastasis. Hence, we aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration. METHODS: Clinical information and RNA-sequencing data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and ArrayExpress datasets. Key GRGs were finally selected through univariate COX, LASSO and multivariate COX regression analyses. External and internal verifications were further carried out to verify our established signature. RESULTS: Finally, 10 GRGs including ANKZF1, CD44, CHST6, HS6ST2, IDUA, KIF20A, NDST3, PLOD2, VCAN, FBP1 were selected out and utilized to establish a novel signature. Compared with the low-risk group, ccRCC patients in high-risk groups showed a lower overall survival (OS) rate (P = 5.548Ee-13) and its AUCs based on our established signature were all above 0.70. Univariate/multivariate Cox regression analyses further proved that this signature could serve as an independent prognostic factor (all P < 0.05). Moreover, prognostic nomograms were also created to find out the associations between the established signature, clinical factors and OS for ccRCC in both the TCGA and ArrayExpress cohorts. All results remained consistent after external and internal verification. Besides, nine out of 21 tumor-infiltrating immune cells (TIICs) were highly related to high- and low- risk ccRCC patients stratified by our established signature. CONCLUSIONS: A novel signature based on 10 prognostic GRGs was successfully established and verified externally and internally for predicting OS of ccRCC, helping clinicians better and more intuitively predict patients' survival.

Integrated Analysis of the Prognosis-Associated RNA-Binding Protein Genes and Candidate Drugs in Renal Papillary Cell Carcinoma.

RNA-binding proteins (RBPs) play significant roles in various cancer types. However, the functions of RBPs have not been clarified in renal papillary cell carcinoma (pRCC). In this study, we identified 31 downregulated and 89 upregulated differentially expressed RBPs on the basis of the cancer genome atlas (TCGA) database and performed functional enrichment analyses. Subsequently, through univariate Cox, random survival forest, and multivariate Cox regression analysis, six RBPs of SNRPN, RRS1, INTS8, RBPMS2, IGF2BP3, and PIH1D2 were screened out, and the prognostic model was then established. Further analyses revealed that the high-risk group had poor overall survival. The area under the curve values were 0.87 and 0.75 at 3 years and 0.78 and 0.69 at 5 years in the training set and test set, respectively. We then plotted a nomogram on the basis of the six RBPs and tumor stage with the substantiation in the TCGA cohort. Moreover, we selected two intersectant RBPs and evaluate their biological effects by GSEA and predicted three drugs, including STOCK1N-28457, pyrimethamine, and trapidil by using the Connectivity Map. Our research provided a novel insight into pRCC and improved the determination of prognosis and individualized therapeutic strategies.

High expression of CDCA7 predicts poor prognosis for clear cell renal cell carcinoma and explores its associations with immunity.

BACKGROUND: Cell division cycle-associated 7 (CDCA7), as a member of the cell division cycle associated family, was reported to be aberrantly expressed in both solid tumors and hematological tumors, suggesting its essential role in promoting tumorigenesis. Hence, we aimed to explore its comprehensive roles of overall survival (OS) in clear cell renal cell carcinoma (ccRCC) and emphasize its associations with immunity. METHODS: The RNA sequencing data and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was adopted to explore CDCA7 associated signaling pathways. Univariate and multivariate Cox regression analyses were carried out to assess independent prognostic factors. Furthermore, roles of CDCA7 in human immunity were also investigated. RESULTS: Our results suggested that CDCA7 was overexpressed in ccRCC and its elevated expression was related to shorter OS (P < 0.01). Univariate and multivariate Cox regression analyses identified CDCA7 as an independent prognostic factor (both P < 0.05). The prognostic nomogram integrating CDCA7 expression level and clinicopathologic variables was constructed to predict 1-, 3- and 5-year OS. GSEA indicated that high CDCA7 expression was related to the apoptosis pathway, cell cycle pathway, JAK-STAT pathway, NOD like receptor pathway, P53 pathway, T cell receptor pathway and toll like receptor pathway, etc. Moreover, CDCA7 was significantly related to microsatellite instability (MSI, P < 0.001) and tumor mutational burden (TMB, P < 0.001). As for immunity, CDCA7 was remarkably associated with immune infiltration, tumor microenvironment, immune checkpoint molecules and immune pathways. CONCLUSIONS: CDCA7 could serve as an independent prognostic factor for ccRCC and it was closely related to MSI, TMB, and immunity.

Decreased expression of METTL14 predicts poor prognosis and construction of a prognostic signature for clear cell renal cell carcinoma.

BACKGROUND: METTL14, as one of N6-methyladenosine (m6A) related genes, has been found to be associated with promoting tumorigenesis in different types of cancers. This study was aimed to investigate the prognostic value of METTL14 in clear cell renal cell carcinoma (ccRCC). METHODS: We collected ccRCC patients' clinicopathological parameters information and 13 m6A related genes expression from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were conducted to investigate whether METTL14 could serve as an independent factor correlated with overall survival (OS). Gene Set Enrichment Analysis (GSEA) was carried out to identify METTL14-related signaling pathways. Moreover, a risk score (RS) was calculated to predict the prognosis of ccRCC. Quantitative real-time PCR (qRT-PCR) was also utilized to verify the expression of METTL14 in clinical specimens. RESULTS: Differently expressed m6A related genes were identified between ccRCC tissues and normal tissues. Therein, METTL14 was lowly expressed in ccRCC tissues and verified by qRT-PCR (all p < 0.01). Survival analysis indicated that high expression of METTL14 was associated with better OS (p = 1e-05). GSEA results revealed that high METTL14 expression was enriched in ERBB pathway, MAPK pathway, mTOR pathway, TGF-ß pathway and Wnt pathway. Moreover, METTL14 was proved to be an independent prognostic factor by means of univariate and multivariate Cox regression analyses. Nomogram integrating both the METTL14 expression and clinicopathologic variables was also established to provide clinicians with a quantitative approach for predicting survival probabilities of ccRCC. Furthermore, a METTL14-based riskscore (RS) was developed with significant OS (p = 6.661e-16) and increased AUC of 0.856. Besides, significant correlated genes with METTL14 were also provided. CONCLUSIONS: Our results indicated that METTL14 could serve as a favorable prognostic factor for ccRCC. Moreover, this study also provided a prognostic signature to predict prognosis of ccRCC and identified METTL14-related signaling pathways.

Promoting cell proliferation, cell cycle progression, and glycolysis: Glycometabolism-related genes act as prognostic signatures for prostate cancer.

BACKGROUND: The Warburg effect seen in most solid tumors occurs only in the late stages of prostate cancer (PCa). Currently, the management of patients with low-risk localized PCa and patients after radical therapy remains a challenge. Our objective here was to evaluate glycometabolism-related genes as prognostic signatures for PCa. METHODS: The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases and glycometabolism-related gene sets were obtained online. Glycometabolic prognostic signatures were identified and validated in a TCGA cohort and tested in an ICGC cohort. We used the gene set enrichment analysis to reveal biological processes associated with the glycometabolism-related signatures. Novel glycometabolism-related genes were selected for verifying their oncogenic phenotypes in vitro. RESULTS: Two glycometabolic prognostic signatures were applied respectively to construct risk score formulas for PCa. Survival and receiver operating characteristic curve analyses were performed to detect the value of these prognostic signatures. We performed univariate and multivariate Cox regression analyses in the TCGA cohort, demonstrating the independence of the prognostic signatures. Three glycometabolism-related genes were found to be novel PCa-associated genes. These were shown to affect proliferation, cell cycle progression, and glycolysis of DU145 and PC3 cells in different degrees. CONCLUSION: The present research represents the first glycometabolic and high-throughput investigation on PCa, revealing potential biomarkers and treatment targets. We confirm the vital role of glycometabolism in PCa and provide essential resources for future exploration of metabolism in PCa.

Prognostic model of 10 immune-related genes and identification of small molecule drugs in bladder urothelial carcinoma (BLCA).

BACKGROUND: We aimed to establish an immune-related gene (IRG) based signature that could provide guidance for clinical bladder cancer (BC) prognostic surveillance. METHODS: Differentially expressed IRGs and transcription factors (TFs) between BCs and normal tissues were extracted from transcriptome data downloaded from the TCGA database. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to identify related pathways based on differently expressed IRGs. Then, univariate Cox regression analysis was performed to investigate IRGs with prognostic values and LASSO penalized Cox regression analysis was utilized to develop the prognostic index (PI) model. RESULTS: A total of 411 BC tissue samples and 19 normal bladder tissues in the TCGA database were enrolled in this study and 259 differentially expressed IRGs were identified. Networks between TFs and IRGs were also provided to seek the upstream regulators of differentially expressed IRGs. By means of univariate Cox regression analysis, 57 IRGs were analyzed with prognostic values and 10 IRGs were finally identified by LASSO penalized Cox regression analysis to construct the PI model. This model could significantly classified BC patients into high-risk group and low-risk group in terms of OS (P=9.923e-07) and its AUC reached 0.711. By means of univariate and multivariate COX regression analysis, this PI was proven to be a valuable independent prognostic factor (HR =1.119, 95% CI =1.066-1.175, P<0.001). CMap database analysis was also utilized to screen out 10 small molecules drugs with the potential for the treatment of BC. CONCLUSIONS: Our study successfully provided a novel PI based on IRGs with the potential to predict the prognosis of BC and screened out 10 small molecules drugs with the potential to treat BC. Besides, networks between TFs and IRGs were also displayed to seek its upstream regulators for future researches.

miR-483-3p, Mediated by KLF9, Functions as Tumor Suppressor in Testicular Seminoma via Targeting MMP9.

BACKGROUND: Seminoma (SEM) is the most frequent testicular germ cell tumor with a high incidence in young men. The present study aims to explore the function and regulatory mechanism of miR-483-3p in SEM. METHODS: RT-qPCR was performed to investigate miR-483-3p levels in SEM tissues. The effect of miR-483-3p on TCam-2 cells was assessed by CCK-8, colony formation, cell migration, and invasion assays. Luciferase reporter assays were performed to investigate the interaction between miR-483-3p and MMP9, and then the recovery experiments were performed. Moreover, the potential upstream regulator of miR-483-3p was predicted based on JASPAR database. RESULTS: miR-483-3p was down-regulated in SEM tissues versus paracancerous normal tissues. The expression level of miR-483-3p was significantly associated with tumor stage by RT-qPCR. Functionally, miR-483-3p over-expression suppressed cell growth, migration, and invasion in SEM cell lines. Mechanically, miR-483-3p negatively regulated MMP9 by directly binding to its 3'-UTR. The over-expression of miR-483-3p could reverse the promoting role of MMP9 over-expression on the proliferation, migration, and invasion of TCam-2 cells. Moreover, KLF9 was identified as a potential upstream regulator of miR-483-3p and functions as a tumor suppressor. CONCLUSIONS: In general, our study suggested that miR-483-3p could inhibit the cell growth, migration, and invasion of testicular SEM by targeting MMP9. Moreover, KLF9 is an upstream positive regulator of miR-483-3p and also functions as a tumor suppressor in SEM.

Genetic variations in MAGE-A11 predict the risk and survival of renal cell cancer.

Melanoma antigen-A11 (MAGE-A11) is a low-abundance, primate-specific steroid receptor coregulator in normal tissues of the human reproductive tract, which plays an important role in tumorigenesis. Single-nucleotide polymorphisms (SNPs) have been shown to contribute to cancer risk and prognosis. However, the role of SNPs of MAGE-A11 in renal cell carcinoma (RCC) has not been established. Two intronic SNPs (rs6641352 and rs6540341) of MAGE-A11 have been screened to assess their associations with RCC risk and prognosis in a case control study. We found that rs6641352 was associated with RCC susceptibility in the dominant model (TC/CC vs. TT, adjusted odds ratio = 1.315, 95% confidence interval [CI] = 1.089-1.588) and with survival of RCC in the recessive model (CC vs. TT/TC, adjusted hazard ratio = 3.526, 95% CI = 1.072-11.595). For the SNP rs6540341, individuals with the T allele could have a critically increased risk of RCC (adjusted odds ratio = 1.301, 95% CI = 1.081-1.564, P = 0.005 in the dominant model). However, there was no significant association between rs6540341 and RCC survival. Hence, rs6641352 in MAGE-A11 may contribute to the genetic susceptibility and prognosis for RCC and act as a biomarker for RCC occurrence and prognosis.

Treatment of Mullerian duct cyst by combination of transurethral resection and seminal vesiculoscopy: An initial experience.

The major purpose of the present study was to investigate the efficacy and feasibility of the Mullerian duct cyst treatment by transurethral electrotomy combined with seminal vesiculoscopy. The clinical data of 20 aspermia patients who presented with Mullerian Cyst between March 2009 and March 2016 were retrospectively analyzed in the present study. Semen specimens of all patients were obtained by masturbation or sperm collector and diagnosed as aspermia by semen analysis (including sperm count, semen volume, sperm density, pH and fructose level). By transrectal ultrasonography, magnetic resonance imaging and testicular biopsy, the diagnosis of Mullerian cyst inducing obstruction aspermia was correctly identified. All patients were treated with the combination of transurethral resection and seminal vesiculoscopy. The operation time was 30-50 min. The follow-up duration after the operation was 12 months. All subjects included in the present study successfully underwent the operation. The semen quality of all patients was greatly improved and sperms were detected in semen specimens. The semen routine examination results of 3 consecutive follow-up exams within 12 months were within the normal range. The ejaculate volume and semen fructose levels were significantly higher than those prior to surgery (P<0.05). Furthermore, at 12 months post-operatively, the seminal vesicles of 6 patients were smaller than at the pre-operative stage. In conclusion, transurethral resection combined with seminal vesiculoscopy may be an effective and feasible option for the treatment of patients with Mullerian duct cyst.

Comparison of prostate cancer detection rates between magnetic resonance imaging-targeted biopsy and transrectal ultrasound-guided biopsy according to Prostate Imaging Reporting and Data System in patients with PSA ≥4 ng/mL: a systematic review and meta-analysis.

BACKGROUND: Previous studies have investigated magnetic resonance imaging-targeted biopsy (MRI-TBx) on the detection for prostate cancer (PCa). Prostate Imaging Reporting and Data System (PI-RADS), as a standardized MRI reporting system, has widely been used in the management of PCa. However, basing the PI-RADS score, the comparability between MRI-TBx and transrectal ultrasound-guided biopsy (TRUS-Bx) in diagnosing PCa remained inconsistent or even controversial. Thus, this systematic meta-analysis aimed to assess the value of PI-RADS in sifting better prostate biopsy method. METHODS: A meta-analysis including 10 articles was performed. In these included studies, biopsy-naive subjects with concerning PSA levels and/or an abnormal digital rectal examination (DRE) were consecutively enrolled by referral from urologists. All subjects underwent multiparameter MRI (mpMRI) prostate and the results were scored independently by PI-RADS. Subjects with equivocal (PI-RADS 3) and intermediate/high-risk (PI-RADS 4/5) lesions underwent MRI-TBx and followed by TRUS-Bx performed by a urologist. The online databases PubMed, Embase and Web of Science were searched to find all correlated articles until October 1st, 2019. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the associations. Subgroup analyses were conducted based on Gleason score. RESULTS: Overall, 10 studies were included in this meta-analysis from January, 2015 to June, 2019. In the comparison of the detection of MRI-TBx and TRUS-Bx in PCa patients, TRUS-Bx had a significant advantage in overall PCa detection compared with MRI-TBx (OR =0.78, 95% CI: 0.62-0.98) in PI-RADS 3. Basing subgroup analysis of Gleason score (csPCa: Gleason score ≥7; non-csPCa: Gleason score <7), a summary analysis of the detection rate of csPCa showed that no significant difference was found (OR =0.82, 95% CI: 0.58-1.16); Meanwhile, no significant difference in non-csPCa patients was also detected (OR =0.83, 95% CI: 0.53-1.28). In PI-RADS 4 or 5, no significant results were detected between MRI-TBx and TRUS-Bx (OR =0.96, 95% CI: 0.87-1.06) for overall PCa detection. The stratification analyses by Gleason score found that TRUS-Bx had an advantage over MRI-TBx in non-csPCa patients (OR =0.76, 95% CI: 0.60-0.98); However, there was no significant difference in the detection rate of csPCa (OR =1.05, 95% CI: 0.93-1.20). CONCLUSIONS: This meta-analysis indicated that using TRUS-Bx was better than MRI-TBx for the diagnosis of PCa in PI-RADS 3; Besides, TRUS-Bx have an advantage over MRI-TBx in the detection for non-csPCa in PI-RADS 4 or 5. Therefore, PI-RADS could be used as a MRI evaluation system in the selection of prostate biopsy.

Metabolomic Profiling of Human Spermatozoa in Idiopathic Asthenozoospermia Patients Using Gas Chromatography-Mass Spectrometry.

The purpose of this study was to describe the first metabolic profile of human sperm cells through the application of an untargeted platform based on gas chromatography-mass spectrometry (GC-MS). Sperm cell samples from patients diagnosed with idiopathic asthenozoospermia (n = 30) and healthy subjects (n = 30) were analyzed using a nontargeted metabolomics method based on GC-MS spectroscopy. The mass spectrometric data were collected using multivariate and univariate analyses to identify metabolites related to idiopathic asthenozoospermia. By using metabolomic strategies, we identified 33 metabolites, 27 of which were decreased in the idiopathic asthenozoospermia group compared with the normozoospermic group and six were increased in idiopathic asthenozoospermia. With respect to human sperm cells, some of these metabolites are reported here for the first time. Pathways for nucleoside, amino acid and energy metabolism, and the Krebs cycle were disturbed and were associated with idiopathic asthenozoospermia. The metabolic profiling provides an important first step in studying the pathophysiological mechanisms involved in IAS, and the identified metabolites may become potential biomarkers for its diagnosis and treatment.

Overexpression of CAPN2 promotes cell metastasis and proliferation via AKT/mTOR signaling in renal cell carcinoma.

The calpain 2 (CAPN2) is upregulated in various malignant carcinomas. Previous studies have reported that CAPN2 functioned as an oncogenic factor in human cancers. However, its clinical role and potential effects on cell metastasis and proliferation in renal cell carcinoma (RCC) remain unknown. In this study, we evaluated the mRNA and protein levels of CAPN2 in human RCC specimens, matched normal specimens, and RCC cell lines using quantitative Real-time PCR (RT-PCR) and western blot. Immunohistochemistry of 74 RCC tissues in a tissue microarrays (TMAs) and normal kidney tissues were performed. Kaplan-Meier survival curve analyses were conducted to measure the correlation between CAPN2 and tumor prognosis. Cell migration, invasion and proliferation were detected by transwell assays and Cell Counting Kit-8 (CCK-8) assays. CAPN2 exhibited a significant overexpression in human RCC tissues and cell lines compared with adjacent non-tumor tissues and normal human proximal tubule epithelial cell line HK-2. Strong staining of CAPN2 was associated with higher clinical stage and histological grade. In addition, sh-CAPN2 could significantly inhibit migration, invasion and proliferation of 769-P and CAKI-1 cells. Conversely, increased cell biological behaviors were observed in CAPN2-OV CAKI-2 cells. Moreover, the subsequent mechanism investigation suggested that CAPN2 promoted tumor progression by activating AKT/mTOR signaling, enhancing epithelial mesenchymal transition (EMT) and MMP9 levels. The present study indicates that CAPN2 may act as a prominent indicator for RCC progression and a novel therapeutic target for RCC patients.