Identification of tumor immunophenotypes associated with immunotherapy response in bladder cancer.

OBJECTIVES: This study aims to reveal immunophenotypes associated with immunotherapy response in bladder cancer, identify the signature genes of immune subtypes, and provide new molecular targets for improving immunotherapy response. METHODS: Bladder cancer immunophenotypes were characterized in the bulk RNA sequencing dataset GSE32894 and Imvigor210, and gene expression signatures were established to identify the immunophenotypes. Expression of gene signatures were validated in single-cell RNA sequencing dataset GSE145140 and human proteins expression data source. Investigation of Immunotherapy Response was performed in IMvigor210 dataset. Prognosis of tumor immunophenotypes was further analyzed. RESULTS: Inflamed and immune-excluded immunophenotypes were characterized based on the tumor immune cell scores. Risk score models that were established rely on RNA sequencing profiles and overall survival of bladder cancer cohorts. The inflamed tumors had lower risk scores, and the low-risk tumors were more likely to respond to atezolizumab, receiving complete response/partial response (CR/PR). Patients who responded to atezolizumab had higher SRRM4 and lower NPHS1 and TMEM72 expression than the non-responders. SRRM4 expression was a protective factor for bladder cancer prognosis, while the NPHS1 and TMEM72 showed the opposite pattern. CONCLUSION: This study provided a novel classification method for tumor immunophenotypes. Bladder cancer immunophenotypes can predict the response to immune checkpoint blockade. The immunophenotypes can be identified by the expression of signature genes.

A study comparing dusting to basketing for renal stones ≤ 2 cm during flexible ureteroscopy

ABSTRACT Objectives To compare the dusting efficiency and safety with basketing for treating renal stones ≤ 2 cm during flexible ureteroscopy (fURS). Materials and methods This study included 218 patients with renal stones ≤ 2 cm treated with fURS. Among them, 106 patients underwent dusting, and 112 patients underwent fragmentation with basket extraction. All patients were followed up for 3 months postoperatively. The operating time, lasing time, stone-free rate (SFR) and complication rate were compared. Results The mean stone size in the dusting group was 1.3 cm, whereas 1.4 cm in the basketing group. The mean operative time was significantly lower in the dusting group than in the basketing group (43.1±11.7 minutes VS 60.5±13.4 minutes, P <0.05), but the lasing time was significantly longer for the dusting group than for the basketing group (17.7±3.9 minutes VS 14.1±3.6 minutes, P <0.05). SFR was significantly higher in the basketing group immediately after the operation and follow-up after 1 month (76.8% vs 55.7%, P= 0.001 and 88.4% vs 78.3%, P = 0.045). However, the SFR was similar for both groups (88.8% in the dusting group vs. 90.2% in the basketing group) after 3 months postoperatively. There was no statistical difference in the complication rates between the two groups. Conclusions Dusting has advantages in shortening the operation time and reducing the operation cost, but the lasing time was longer compared with the basketing. Although there is no difference in long-term effect, basketing is superior to dusting in terms of short-term SFR. Moreover, dusting should be avoided in some special cases and basketing a better choice. Both techniques are effective for the treatment of renal stones ≤ 2 cm and choice depends on patient demographic and stone characteristics.

Establishment of a risk score model for bladder urothelial carcinoma based on energy metabolism-related genes and their relationships with immune infiltration.

Bladder urothelial carcinoma (BLCA) is a common malignant tumor of the human urinary system, and a large proportion of BLCA patients have a poor prognosis. Therefore, there is an urgent need to find more efficient and sensitive biomarkers for the prognosis of BLCA patients in clinical practice. RNA sequencing (RNA-seq) data and clinical information were obtained from The Cancer Genome Atlas, and 584 energy metabolism-related genes (EMRGs) were obtained from the Reactome pathway database. Cox regression analysis and least absolute shrinkage and selection operator analysis were applied to assess prognostic genes and build a risk score model. The estimate and cibersort algorithms were used to explore the immune microenvironment, immune infiltration, and checkpoints in BLCA patients. Furthermore, we used the Human Protein Atlas database and our single-cell RNA-seq datasets of BLCA patients to verify the expression of 13 EMRGs at the protein and single-cell levels. We constructed a risk score model; the area under the curve of the model at 5 years was 0.792. The risk score was significantly correlated with the immune markers M0 macrophages, M2 macrophages, CD8 T cells, follicular helper T cells, regulatory T cells, and dendritic activating cells. Furthermore, eight immune checkpoint genes were significantly upregulated in the high-risk group. The risk score model can accurately predict the prognosis of BLCA patients and has clinical application value. In addition, according to the differences in immune infiltration and checkpoints, BLCA patients with the most significant benefit can be selected for immune checkpoint inhibitor therapy.

A study comparing dusting to basketing for renal stones ≤ 2 cm during flexible ureteroscopy.

OBJECTIVES: To compare the dusting efficiency and safety with basketing for treating renal stones ≤ 2 cm during flexible ureteroscopy (fURS). MATERIALS AND METHODS: This study included 218 patients with renal stones ≤ 2 cm treated with fURS. Among them, 106 patients underwent dusting, and 112 patients underwent fragmentation with basket extraction. All patients were followed up for 3 months postoperatively. The operating time, lasing time, stone-free rate (SFR) and complication rate were compared. RESULTS: The mean stone size in the dusting group was 1.3 cm, whereas 1.4 cm in the basketing group. The mean operative time was significantly lower in the dusting group than in the basketing group (43.1±11.7 minutes VS 60.5±13.4 minutes, P < 0.05), but the lasing time was significantly longer for the dusting group than for the basketing group (17.7±3.9 minutes VS 14.1±3.6 minutes, P < 0.05). SFR was significantly higher in the basketing group immediately after the operation and follow-up after 1 month (76.8% vs 55.7%, P= 0.001 and 88.4% vs 78.3%, P = 0.045). However, the SFR was similar for both groups (88.8% in the dusting group vs. 90.2% in the basketing group) after 3 months postoperatively. There was no statistical difference in the complication rates between the two groups. CONCLUSIONS: Dusting has advantages in shortening the operation time and reducing the operation cost, but the lasing time was longer compared with the basketing. Although there is no difference in long-term effect, basketing is superior to dusting in terms of short-term SFR. Moreover, dusting should be avoided in some special cases and basketing a better choice. Both techniques are effective for the treatment of renal stones ≤ 2 cm and choice depends on patient demographic and stone characteristics.

Integrative Single-Cell Analysis Reveals Transcriptional and Epigenetic Regulatory Features of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) frequently features a high level of tumor heterogeneity. Elucidating the chromatin landscape of ccRCC at the single-cell level could provide a deeper understanding of the functional states and regulatory dynamics underlying the disease. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on 19 ccRCC samples, and whole-exome sequencing was used to understand the heterogeneity between individuals. Single-cell transcriptome and chromatin accessibility maps of ccRCC were constructed to reveal the regulatory characteristics of different tumor cell subtypes in ccRCC. Two long noncoding RNAs (RP11-661C8.2 and CTB-164N12.1) were identified that promoted the invasion and migration of ccRCC, which was validated with in vitro experiments. Taken together, this study comprehensively characterized the gene expression and DNA regulation landscape of ccRCC, which could provide new insights into the biology and treatment of ccRCC. SIGNIFICANCE: A comprehensive analysis of gene expression and DNA regulation in ccRCC using scATAC-seq and scRNA-seq reveals the DNA regulatory programs of ccRCC at the single-cell level.

Long noncoding RNA as a potential diagnostic tool for prostate cancer: a systematic review and meta-analysis.

PURPOSE: To identify consistently expressed lncRNAs and suitable lncRNAs with high sensitivity and specificity from multiple independent studies as potential biomarkers for PCa diagnostics. METHODS: We searched multiple electronic databases including PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, CQVIP, Wanfang, and CBMdisc for studies published up to July 2022. The quality of the included studies was assessed by two independent reviewers based on the QUADAS-2 tool using Review Manager 5.3. A vote-counting method was used based on the ranking of potential molecular biomarkers. The top-ranked lncRNAs were further assessed for diagnostic value using Meta-disc version 1.4 software. RESULTS: Among the 26 included studies, 2 circulating lncRNAs (PCA3 and MALAT-1) were reported 3 or more times in PCa patients versus non-PCa patients. In further analysis, the areas under the curve of the summary receiver operating characteristic curves for PCA3 and MALAT-1 distinguishing PCa patients were 0.775 and 0.771, respectively. CONCLUSIONS: Based on the current evidence, PCA3 and MALAT-1 are reliable lncRNAs for the diagnosis of PCa.

Machine learning model for the prediction of prostate cancer in patients with low prostate-specific antigen levels: A multicenter retrospective analysis.

Objective: The aim of this study was to develop a predictive model to improve the accuracy of prostate cancer (PCa) detection in patients with prostate specific antigen (PSA) levels ≤20 ng/mL at the initial puncture biopsy. Methods: A total of 146 patients (46 with Pca, 31.5%) with PSA ≤20 ng/mL who had undergone transrectal ultrasound-guided 12+X prostate puncture biopsy with clear pathological results at the First Affiliated Hospital of Guangxi Medical University (November 2015 to December 2021) were retrospectively evaluated. The validation group was 116 patients drawn from Changhai Hospital(52 with Pca, 44.8%). Age, body mass index (BMI), serum PSA, PSA-derived indices, several peripheral blood biomarkers, and ultrasound findings were considered as predictive factors and were analyzed by logistic regression. Significant predictors (P < 0.05) were included in five machine learning algorithm models. The performance of the models was evaluated by receiver operating characteristic curves. Decision curve analysis (DCA) was performed to estimate the clinical utility of the models. Ten-fold cross-validation was applied in the training process. Results: Prostate-specific antigen density, alanine transaminase-to-aspartate transaminase ratio, BMI, and urine red blood cell levels were identified as independent predictors for the differential diagnosis of PCa according to multivariate logistic regression analysis. The RandomForest model exhibited the best predictive performance and had the highest net benefit when compared with the other algorithms, with an area under the curve of 0.871. In addition, DCA had the highest net benefit across the whole range of cut-off points examined. Conclusion: The RandomForest-based model generated showed good prediction ability for the risk of PCa. Thus, this model could help urologists in the treatment decision-making process.

Single-Cell RNA Sequencing of Metastatic Testicular Seminoma Reveals the Cellular and Molecular Characteristics of Metastatic Cell Lineage.

Background: Testicular cancer is the most common solid malignancy in young men. Given the many histological classifications of testicular tumors, seminoma is one of the most treatable cancers. The survival rate in early-stage disease was more than 90%. Thus, seminoma at the cellular and molecular levels, especially at the single-cell level, is worth studying. Methods: We performed a single-cell RNA sequencing (scRNA-seq) study on a patient who was diagnosed with testicular seminoma with lymph node metastasis. This study presented tumor tissue, PBMC, pelvic and renal hilus lymph node in a total of 18,206 high-quality single-cell transcriptome information. The characteristics of metastatic cell lineage were revealed by the comparison between different tumor cell subtypes at the scRNA level. Results: A single-cell map of testicular seminoma with lymph node metastasis was constructed by scRNA-seq. We discovered the gene expression characteristics of the tumor cells in testicular seminoma, especially metastatic tumor cells. KRT8 and KRT18 were commonly expressed in the three tumor cell subtypes. However, TCF7L1, SCG3 and SV2C were the specifically expressed genes of tumor cell subtypes in primary tumor sites. Some molecular markers specifically expressed by the metastatic cell lineage, such as POU5F1, were identified. Conclusions: We revealed the molecular characteristics of testicular seminoma at the single-cell level, especially the metastatic tumor cells. This study could provide new insights into the diagnosis and treatment of testicular seminoma.

Single-cell transcriptomics reveals cell type diversity of human prostate.

Extensive studies have been performed to describe the phenotypic changes occurring during malignant transformation of the prostate. However, the cell types and associated changes that contribute to the development of prostate diseases and cancer remain elusive, largely due to the heterogeneous composition of prostatic tissues. Here, we conduct a comprehensive evaluation of four human prostate tissues by single-cell RNA sequencing (scRNA-seq) to analyze their cellular compositions. We identify 18 clusters of cell types, each with distinct gene expression profiles and unique features; of these, one cluster of epithelial cells (Ep) is found to be associated with immune function. In addition, we characterize a special cluster of fibroblasts and aberrant signaling changes associated with prostate cancer (PCa). Moreover, we provide insights into the epithelial changes that occur during the cellular senescence and aging. These results expand our understanding of the unique functional associations between the diverse prostatic cell types and the contributions of specific cell clusters to the malignant transformation of prostate tissues and PCa development.

Single-cell transcriptomes reveal characteristic features of cell types within the human adrenal microenvironment.

Various cells within the adrenal microenvironment are important in maintaining the body homeostasis. However, our understanding of adrenal disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ's multiple homeostatic functions. We report a cellular landscape of the human adrenal gland using single-cell RNA sequencing. We reveal characteristic features of cell types within the human adrenal microenvironment and found immune activation of nonimmune cells in the adrenal endothelial cells. We also reveal that abundant immune cells occupied a lot of space in adrenal gland. Additionally, Sex-related diversity in the adrenocortical cells and different gene expression profiles between the left and right adrenal gland are also observed at single-cell resolution. Together, at single-cell resolution, the transcriptomic map presents a comprehensive view of the human adrenal gland, which serves as a fundamental baseline description of this organ and paves a way for the further studies of adrenal diseases.

[Reduced zinc concentration in expressed prostatic secretion relates to the pain symptoms of types â ¢ and â £ prostatitis].

OBJECTIVE: To determine the zinc levels in the expressed prostatic secretion (EPS) of the patients with different types of chronic nonbacterial prostatitis, and explore the reference value of zinc concentration in EPS in the diagnosis and treatment of prostatitis. METHODS: We collected EPS samples from 35 healthy men and 173 patients with chronic nonbacterial prostatitis, including 65 cases of type ⅢA, 69 cases of type ⅢB, and 39 cases of type Ⅳ, according to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). We compared the zinc levels in the EPS samples among different groups and analyzed the correlations of zinc concentration with the NIH-CPSI scores, WBC count, pH value, and age of the subjects. RESULTS: The participants were aged 17－65 (32.5±8.5) years. The zinc concentrations in the EPS were significantly lower in the ⅢA (ï¼»162.2±10.8ï¼½ µg/ml) and ⅢB (ï¼»171.2±12.0ï¼½ µg/ml) than in the Ⅳ (ï¼»234.6±17.9ï¼½ µg/ml) (P<0.05 ) and the control group (ï¼»259.5±14.6ï¼½ µg/ml) (P<0.05 ). The zinc level was correlated negatively with the NIH-CPSI pain score (r=－0.248, P<0.01), quality of life score (r=－0.232, P<0.01), severity score (r=－0.270, P<0.01), total NIH-CPSI score (r=－0.281, P<0.01), and the pH value in EPS (r=－0.208, P<0.01), but showed no correlation with the WBC count and age of the subjects. CONCLUSIONS: The reduced zinc concentration in the EPS of the patients with chronic nonbacterial prostatitis may be associated with the pain symptoms of the disease, which suggests the potential reference value of measuring the zinc concentration in EPS in the diagnosis and treatment of prostatitis.

[A multi-omics study on NKX3.1-related node genes in prostate cancer].

Objective: The NKX3.1 homeobox gene is closely associated with the development and progression of prostate cancer. This study was to explore NKX3.1-related down-stream node genes and their possible regulating mechanisms in prostate cancer. Methods: By multi-omics analysis of the TCGA data on prostate cancer,we screened 5 node genes in the down-stream signaling pathways that were possibly related to NKX3.1.We achieved the overexpression of NKX3.1 in prostate cancer by transfecting the prostate cancer PC-3 cell lines with the NKX3.1 expression vector and determined the expression levels of the node genes by real-time PCR. Results: Based on the results of multi-omics analysis,MAZ,LPAR3,TUBB2A,CAMKK2 and CPT1B were identified as the node genes involved in the NKX3.1-related signaling pathways in prostate cancer. The NKX3.1 overexpression experiments showed that the CAMKK2 and CPT1B genes were up-regulated 3. 439 and 4. 641 times respectively and the MAZ gene down-regulated 5.236 times in the prostate cancer PC-3 cells with the overexpression of NKX3.1. Conclusion: NKX3.1 may suppress the development and progression of prostate cancer by down-regulating the expression of MAZ and up-regulating those of CAMKK2 and CPT1B,and it may also be involved in the regulation of the metabolic process of prostate cancer through the CAMKK2 down-stream signaling pathway and CPT1B.

Genetic variations affecting serum carcinoembryonic antigen levels and status of regional lymph nodes in patients with sporadic colorectal cancer from Southern China.

BACKGROUND: Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications. METHODS AND FINDINGS: Genome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI Taqman platform. Eight candidate SNPs were validated in CRC patients. The rs1047781 (chr19- FUT2) (A/T) was associated with elevated sCEA levels, and rs8176746 (chr9- ABO) was associated with the regional lymph metastasis in the CRC patients. The preoperative sCEA level was a risk factor for tumor recurrence in 5 years after operation (OR = 1.427, 95% CI: 1.005∼1.843, P = 0.006). It was also one of the risk factors for regional lymph node metastasis (OR = 2.266, 95% CI: 1.196∼4.293, P = 0.012). The sCEA level in rs1047781-T carriers was higher than that in the A carriers in CRC patients without lymph node metastasis (P = 0.006). The regional lymph node metastasis in patients with homozygote AA of rs8176746 was more common than that in the heterozygote AG carriers (P = 0.022). In addition, rs1047781-AT and TT CRC patients exhibited a worse disease-free survival than AA genotype carriers (P = 0.023). CONCLUSIONS: We found candidate SNPs associated with elevated sCEA levels in both healthy males and CRC population. Rs1047781 (chr19- FUT2) may be the susceptible locus for recurrence of CRC in a population from Southern China.

Antineoplastic effect of calycosin on osteosarcoma through inducing apoptosis showing in vitro and in vivo investigations.

Recently, increasing studies have documented that tumorigenesis closely relates to apoptotic processes. Thus, inducing apoptosis is an anti-cancer strategy against osteosarcoma. Here we investigated the anti-proliferative effect of calycosin on human osteosarcoma cell (143B) in vitro. The results showed that calycosin dose-dependently inhibited 143B cell proliferation as reflected in tetrazolium salt (MTT) assay (P<0.01). In addition, calycosin effectively down-regulated cellular mRNA expressions of IκBα, NF-κB p65 and cyclin D1 through RT-PCR assay (P<0.01). Next, calycosin-mediated inhibitory effect on 143B tumor-bearing nude mice and the underlying mechanism were evaluated and discussed. As a result, calycosin administration significantly blocked solid tumor growth in 143B-harbored nude mice (P<0.01). Furthermore, intracellular Bcl-2 protein expression was effectively reduced in 143B-harbored tumor tissue through western blotting analysis (P<0.01), while intratumoral Apaf-1 and cleaved Caspase-3 protein levels were up-regulated, respectively (P<0.01). Taken together, calycosin possesses the anti-osteosarcoma potential, in which the mechanism involved was associated with activation of apoptotic, thus inducing apoptosis.

Formononetin protects TBI rats against neurological lesions and the underlying mechanism.

Traumatic brain injury (TBI) is a major cause of disability or death worldwide, especially in the young. Thus, effective medication with few side effects needs to be developed. This work aimed to explore the potential benefits of formononetin (FN) on TBI rodent model and to discuss the regarding mechanism. These findings showed that FN effectively increased the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in brain tissue of TBI rats (P<0.01), while it reduced intracephalic malonaldehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations (P<0.01). Meanwhile, the hydrocephalus in the TBI rat was alleviated, and the injured nerve cell of the lesioned brain was reduced as showed in hematoxylin-eosin (HE) staining assay. In addition, the endogenous mRNA level of cyclooxygenase-2 (COX-2) in the brain of the TBI rat was significantly down-regulated (P<0.01). Furthermore, the protein expression of nuclear factor E2-related factor 2 (Nrf2) was effectively up-regulated (P<0.01). Taken together, we conclude that formononetin mediates the promising anti-TBI effects against neurocyte damage, which the underlying mechanisms are associated with inhibiting intracephalic inflammatory response and oxidative stress for neuroprotection.

Genome-wide association study of sex hormones, gonadotropins and sex hormone-binding protein in Chinese men.

BACKGROUND: Sex hormones and gonadotropins exert a wide variety of effects in physiological and pathological processes. Accumulated evidence shows a strong heritable component of circulating concentrations of these hormones. Recently, several genome-wide association studies (GWASs) conducted in Caucasians have identified multiple loci that influence serum levels of sex hormones. However, the genetic determinants remain unknown in Chinese populations. In this study, we aimed to identify genetic variants associated with major sex hormones, gonadotropins, including testosterone, oestradiol, follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone binding globulin (SHBG) in a Chinese population. METHODS: A two-stage GWAS was conducted in a total of 3495 healthy Chinese men (1999 subjects in the GWAS discovery stage and 1496 in the confirmation stage). RESULTS: We identified a novel genetic region at 15q21.2 (rs2414095 in CYP19A1), which was significantly associated with oestradiol and FSH in the Chinese population at a genome-wide significant level (p=6.54×10(-31) and 1.59×10(-16), respectively). Another single nucleotide polymorphism in CYP19A1 gene was significantly associated with oestradiol level (rs2445762, p=7.75×10(-28)). In addition, we confirmed the previous GWAS-identified locus at 17p13.1 for testosterone (rs2075230, p=1.13×10(-8)) and SHBG level (rs2075230, p=4.75×10(-19)) in the Chinese population. CONCLUSIONS: This study is the first GWAS investigation of genetic determinants of FSH and LH. The identification of novel susceptibility loci may provide more biological implications for the synthesis and metabolism of these hormones. More importantly, the confirmation of the genetic loci for testosterone and SHBG suggests common genetic components shared among different ethnicities.

Role of metabolic factors in the association between osteocalcin and testosterone in Chinese men.

OBJECTIVE: Osteocalcin can regulate energy metabolism and increase testosterone production. Although previous studies have shown the positive association between osteocalcin and testosterone, the effect of metabolic factors in the association is unclear. DESIGN AND SETTING: Osteocalcin, testosterone, and metabolic factors were accessed in 2400 men aged 20 to 69 years, who participated in the population-based Fangchenggang Area Male Health and Examination Survey in Guangxi province of China from September 2009 to December 2009. MAIN OUTCOME MEASURES: Metabolic syndrome was defined based on the updated report of National Cholesterol Education Program Adult Treatment Panel III criteria. Serum total osteocalcin, total testosterone (TT), and sex hormone binding globulin (SHBG) were measured, whereas free testosterone (FT) and bioavailable testosterone (BT) were calculated based on Vermeulen's formula. The multivariable linear regression analysis was used. RESULTS: Osteocalcin was positively associated with TT, FT, and BT in the unadjusted model (all P < .001). After adjusting for age, the positive association between osteocalcin and TT remained statistically significant (ß = .17, 95% confidence interval = 0.14-0.20) and was not attenuated in each MetS subgroup including hypertriglyceridemia, hyperglycemia, elevated blood pressure, and low high-density lipoprotein cholesterol, while in the group of central obesity (waist circumstance ≥90 cm), the association appeared significantly stronger (ß = 0.21, 95% confidence interval = 0.12-0.30). After further adjusting for SHBG, osteocalcin was positively associated with TT, FT, and BT in men with central obesity or men with any two MetS components (all P < .05). CONCLUSIONS: Serum total osteocalcin is positively associated with testosterone, which is probably modified by SHBG and central obesity.

Both total testosterone and sex hormone-binding globulin are independent risk factors for metabolic syndrome: results from Fangchenggang Area Male Health and Examination Survey in China.

BACKGROUND: Metabolic syndrome is often beneficial from testosterone replacement therapy. Although testosterone and sex hormone-binding globulin (SHBG) are inversely associated with the risk of metabolic syndrome, it is controversial whether the association between testosterone and metabolic syndrome is independent of SHBG. METHODS: Testosterone, SHBG and metabolic syndrome were evaluated in 2361 men aged 20-73 years, who participated in the population-based Fangchenggang Area Male Health and Examination Survey. Total testosterone, SHBG and other biochemical profiles were measured. Free testosterone and bioavailable testosterone were calculated on the basis of Vermeulen's formula. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria for Asian population. The independent associations with metabolic syndrome were determined by multivariate logistic regression analysis. RESULTS: Men with metabolic syndrome had a lower level of total testosterone, bioavailable testosterone, free testosterone, or SHBG than those without metabolic syndrome (all p < 0.001). Both total testosterone and SHBG were inversely correlated with body mass index or homeostasis model assessment of insulin resistance (all age-adjusted p < 0.001). Men within the lowest quartile of total testosterone [odds ratio (OR) = 4.86, 95% confidence interval (CI) = 2.72-8.68], bioavailable testosterone (OR = 3.04, 95% CI = 1.81-5.10), free testosterone (OR = 3.08, 95% CI = 1.81-5.27) or SHBG (OR = 4.28, 95% CI = 2.52-7.27) had a risk of metabolic syndrome after adjusting for age, smoking, homeostasis model assessment of insulin resistance and body mass index. Total testosterone remained inversely associated with metabolic syndrome after further adjusting for SHBG (OR = 0.95, 95% CI = 0.92-0.99), while SHBG remained inversely associated with metabolic syndrome after further adjusting for total testosterone (OR = 0.99, 95% CI = 0.97-1.00). CONCLUSION: Total testosterone and SHBG are independent risk factors of metabolic syndrome. Prospective studies are needed to explore whether the association between sex hormones and metabolic syndrome was mediated by insulin resistance or obesity.

Distribution characteristics of leukocytes in EPS and correlation with serum PSA levels: results from a Chinese male population survey.

OBJECTIVE: To explore the distribution characteristics of leukocytes in expressed prostatic secretions (EPS) in a large Chinese male population and the correlation with leukocytes and prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: From September to December 2009, EPS specimens were collected from 2504 men (age 20-69 years) who had undergone prostatic massage and were recruited from a large-scale community-based population survey in Southern China. The EPS specimens were divided into 5 categories according to the leukocyte count. The lifestyle and demographic characteristics were obtained by questionnaire. Asymptomatic and symptomatic men were defined according to the findings from the National Institutes of Health-Chronic Prostatitis Symptom Index questionnaire. RESULT: EPS specimens were successfully collected from 1779 of the 2504 participants (71%). The degree of inflammation in the EPS specimens progressively increased with age, education, and body mass index (P <.001 for trend for all). A similar result was observed for men living with a partner compared with those living alone (P <.001) but not for men who smoked (P = .084) or consumed alcohol (P = .461). Moreover, a trend for PSA levels increasing progressively across leukocyte categories was observed (P <.001). The PSA levels were greater in all participants with inflammation than in those without (P <.001 for all) when inflammation was defined at 5+, 10+, and 20+ but not for 20+ in asymptomatic men and or not for 5+ and 10+ in symptomatic men. CONCLUSION: The results of the present study have shown that the degree of inflammation in EPS progressively increases with increasing age, body mass index, and education. Moreover, an increase of leukocytes in the EPS specimen correlated with increasing PSA levels. Prospective studies are needed to determine whether the minor elevations have clinical significance for prostatitis assessment.

Genome-wide association study identified novel genetic variant on SLC45A3 gene associated with serum levels prostate-specific antigen (PSA) in a Chinese population.

Prostate-specific antigen (PSA) is a commonly used cancer biomarker for prostate cancer, and is often included as part of routine physical examinations in China. Serum levels of PSA may be influenced by genetic factors as well as other factors. A genome-wide association study (GWAS) conducted in a European population successfully identified six genetic loci that were significantly associated with PSA level. In this study, we aimed to identify common genetic variants that are associated with serum level of PSA in a Chinese population. We also evaluated the effects of those variants by creating personalized PSA cutoff values. A two-stage GWAS of PSA level was performed among men age 20-69 years and self-reported cancer-free participants that underwent routine physical examinations at several hospitals in Guangxi Province, China. Single nucleotide polymorphisms (SNPs) significantly associated with PSA levels in the first stage of sample (N = 1,999) were confirmed in the second stage of sample (N = 1,496). Multivariate linear regression was used to assess the independent contribution of confirmed SNPs and known covariates, such as age, to the level of PSA. SNPs in three regions were significantly associated with levels of PSA in this two-stage GWAS, and had combined P values between 4.62 × 10(-17) and 6.45 × 10(-37). The three regions are located on 1q32.1 at SLC45A3, 10q11.23 at MSMB, and 19q13.33 at KLK3. The region 1q32.1 at SLC45A3 was identified as a novel locus. Genetic variants contributed significantly more to the variance of PSA level than known covariates such as age. Personalized cutoff values of serum PSA, calculated based on the inheritance of these associated SNPs, differ considerably among individuals. Identification of these genetic markers provides new insight into the molecular mechanisms of PSA. Taking individual variation into account, these genetic variants may improve the performance of PSA to predict prostate cancer.