Prognosis Prediction of Disulfidptosis-Related Genes in Bladder Cancer and a Comprehensive Analysis of Immunotherapy.

As a newly discovered mechanism of cell death, disulfidptosis is expected to help diagnose and treat bladder cancer patients. First, data obtained from public databases were analyzed using bioinformatics techniques. SVA packages were used to combine data from different databases to remove batch effects. Then, the differential analysis and COX regression analysis of ten disulfidptosis-related genes identified four prognostically relevant differentially expressed genes which were subjected to Lasso regression for further screening to obtain model-related genes and output model formulas. The predictive power of the prognostic model was verified and the immunohistochemistry of model-related genes was verified in the HPA database. Pathway enrichment analysis was performed to identify the mechanism of bladder cancer development and progression. The tumor microenvironment and immune cell infiltration of bladder cancer patients with different risk scores were analyzed to personalize treatment. Then, information from the IMvigor210 database was used to predict the responsiveness of different risk patients to immunotherapy. The oncoPredict package was used to predict the sensitivity of patients at different risk to chemotherapy drugs, and its results have some reference value for guiding clinical use. After confirming that our model could reliably predict the prognosis of bladder cancer patients, the risk scores were combined with clinical information to create a nomogram to accurately calculate the patient survival rate. A prognostic model containing three disulfidptosis-related genes (NDUFA11, RPN1, SLC3A2) was constructed. The functional enrichment analysis and immune-related analysis indicated patients in the high-risk group were candidates for immunotherapy. The results of drug susceptibility analysis can guide more accurate treatment for bladder cancer patients and the nomogram can accurately predict patient survival. NDUFA11, RPN1, and SLC3A2 are potential novel biomarkers for the diagnosis and treatment of bladder cancer. The comprehensive analysis of tumor immune profiles indicated that patients in the high-risk group are expected to benefit from immunotherapy.

HP1α promotes the progression of prostate cancer.

PURPOSE: Patients who have been diagnosed with prostate cancer (PCa) typically have a dismal outlook and few therapeutic choices available to them, because the precise pathogenesis of the disease is not yet fully understood. The presence of HP1α, also known as the heterochromatin protein 1α, is required for the creation of higher-order chromatin structures. However, little is known about HP1α that serves roles in the pathogenesis of PCa. The primary purpose of our research was to investigate alterations in the levels of HP1α expression and to plan a series of tests to validate the function of HP1α in PCa. METHOD: Information on HP1α expression in PCa and benign prostatic hyperplasia (BPH) tissues were gathered using the Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. RT-qPCR, western blotting, and immunohistochemistry (IHC) were used to assess HP1α mRNA and protein expression in several human PCa tissues and cell lines. The CCK8 assay, clone formation assay, and transwell assay were used to examine biological activities including cell proliferation, migration, and invasion. The expression of proteins connected to apoptosis and the epithelial-mesenchymal transition (EMT) was examined using Western blot. The tumorigenic effect of HP1α was also verified by in vivo experiments. RESULT: HP1α expression was much higher in PCa than in BPH tissues and cells, and was positively correlated with the Gleason score of PCa. In vitro experiments showed that HP1α knockdown could inhibit the ability of proliferation, invasion, and migration of PC3 and LNCaP cells, and promote cell apoptosis and EMT. In vivo experiments showed that HP1α knockdown inhibited tumorigenesis in mice. CONCLUSION: Our findings indicate that HP1α expression promotes PCa development and might be a novel therapeutic target for the diagnosis or treatment of PCa.

[Research progress of SOX9 in the evolution of prostate cancer].

Sex-determining region Y-box transcription factor 9（SOX9）is essential for prostate development. The dysregulation of SOX9 not only affects the occurrence of Prostate cancer (PCa), but also plays a key role in castration-resistant prostate cancer (CRPC). However, the mechanism of SOX9 affecting the evolution of PCa is still unclear. This paper mainly reviews the molecular mechanism and signal pathway related to the occurrence and development of SOX9 and PCa. SOX9 gene may be an important new biomarker in the development of PCa,providing new ideas for clinical diagnosis and treatment.

[Study on the length and quality of prostate biopsy tissue strips].

OBJECTIVE: To improve the diagnostic yield of prostate biopsy, which we can achieve by puncture more sites and number of cores, another way to obtain more tissue is to take longer tissue strips. In this study, we evaluated the effect of strip length on cancer diagnosis by needle biopsy and derived a cutoff value of strip length to improve cancer detection. METHODS: The pathological reports of 754 patients with suspected prostate cancer who underwent transperineal prostate biopsy were retrospectively analyzed. The age, serum prostate specific antigen (PSA), prostate volume, Gleason score and tissue strip length were analyzed. The length of the tissue strip was compared between the biopsy positive patients and the biopsy negative patients, and the patients were divided into group A（biopsy positive group）and group B（biopsy negative group）, respectively. Statistical analysis of tissue strip lengths was performed to determine cutoff values for biopsy length quality. RESULTS: A total of 10 556 tissue strips were obtained from 754 patients, and 45.1 % of the patients were pathologically diagnosed as prostate cancer. The median length of the tissue strip was 10.5 (9.5, 12.5) mm, the median age was 69 (64,75) years, the median PSA was 12.4 (8.6, 20.8) µg/L, and the median prostate volume was 44.8 (30.5, 64.4) ml. The median length of tissue strips in group A and group B was 11 (10,13) mm and 10 (9,12) mm, respectively. Receiver operating characteristic (ROC) curve analysis was performed on the length of tissue strips in all cases, and the cutoff value of quality assurance was 11.8mm, the area under curve (AUC) was 0.82, and the cut-off value of quality assurance was 11.8mm. Sensitivity 71.4%, specificity 73.8%(P<0.001). CONCLUSIONS: In transperineal prostate biopsy, the cancer detection rate of tissue strips may increase with length. The results of ROC analysis showed that 11.8 mm was used as the cut-off value for quality assurance.

[Mendelian randomization of diabetes and prostate cancer risk in East Asian population].

OBJECTIVE: Mendelian randomization (MR) was used to explore the causal relationship between diabetes (type 1 and type 2) and prostate cancer (PCa) in East Asian population. METHODS: Mendelian randomization is a causal inference method based on genetic variation, which uses the influence of randomly assigned genotypes in nature on phenotype to infer the impact of biological factors on diseases. This study used genetic variation genes related to inflammatory biomarkers as instrumental variables to improve inference, and patient data was obtained from the GWAS database's aggregated association results. In the individual sample, we estimated the correlation between instrumental variables (SNPs) and type 1 and type 2 diabetes, and screened out strongly related SNPs, and excluded SNPs related to prostate cancer. After screening, further sensitivity analysis and visualization of research results were carried out to test the blood glucose level and the causal relationship between diabetes and prostate cancer. RESULTS: Our MR analysis found that there was a negative causal relationship between the risk of prostate cancer and type 2 diabetes.The ratio of type 2 diabetes to prostate cancer causal relationship (OR)=1.0039, 95% confidence interval (CI)=(1.0008, 1.0071), P=0.013, while type 1 diabetes had fewer SNPs screened, Failed to conduct relevant follow-up analysis. CONCLUSIONS: Under Mendel's randomization hypothesis, our research results show that in the East East Asian population, the gene predicted type 2 diabetes and the occurrence of prostate cancer have a negative causal relationship, while the causal relationship between type 1 diabetes and prostate cancer is unknown due to the limited number of instrumental variables.

[Transurethral columnar balloon dilation of the prostate for benign prostatic hyperplasia].

OBJECTIVE: To study the clinical effect of transurethral columnar balloon dilation of the prostate (TUCBDP) in the treatment of BPH and introduce the experience with the surgical procedure. METHODS: We retrospectively analyzed the clinical data on 265 cases of BPH treated by TUCBDP from August 2016 to August 2019. RESULTS: Operations were successfully completed in all the cases, with the mean operation time of (24.67 ± 7.6) min and the average intraoperative blood loss of (26.5 ± 21.4) ml, and all the patients had urinary patency after removal of the catheter. Follow-up examinations every 3 months after surgery showed significant improvement over the baseline in IPSS, quality of life score (QOL), maximum urinary flow rate (Qmax), postvoid residual urine (PVR) and other indicators (P < 0.05). Forty-five of the patients with sexual life exhibited no significant difference from the baseline in IIEF-5 and erectile hardness scale (EHS) scores (P > 0.05). Postoperative complications were observed in 53 cases (20%), including 28 cases of transient urinary incontinence (10.56%), 3 cases of hemorrhage (1.13%), 11 cases of urinary tract infection (4.15%), 1 case of urethral stricture (0.37%), and 8 cases of acute urinary retention (3.01%), which were all improved after regular treatment, with no occurrence of true urinary incontinence. Retrograde ejaculation occurred in 2 (4.45%) of the 45 patients with sexual life. CONCLUSIONS: Transurethral columnar balloon dilation of the prostate, with the advantages of short operation time and less intraoperative bleeding, has a significant short-term clinical effect in the treatment of BPH, particularly suitable for the elderly and those who want to retain the sexual function. Intraoperative localization of the protrusion may significantly influence the outcome of surgery, which deserves strengthened studies. Special attention should be paid to the incidence of postoperative transient urinary incontinence.

Management of large renal stones with super-mini percutaneous nephrolithotomy: an international multicentre comparative study.

OBJECTIVES: To comparatively evaluate the clinical outcomes of super-mini percutaneous nephrolithotomy (SMP) and mini-percutaneous nephrolithotomy (Miniperc) for treating urinary tract calculi of >2 cm. PATIENTS AND METHODS: An international multicentre, retrospective cohort study was conducted at 20 tertiary care hospitals across five countries (China, the Philippines, Qatar, UK, and Kuwait) between April 2016 and May 2019. SMP and Miniperc were performed in 3525 patients with renal calculi with diameters of >2 cm. The primary endpoint was the stone-free rate (SFR). The secondary outcomes included: blood loss, operating time, postoperative pain scores, auxiliary procedures, complications, tubeless rate, and hospital stay. Propensity score matching analysis was used to balance the selection bias between the two groups. RESULTS: In all, 2012 and 1513 patients underwent SMP and Miniperc, respectively. After matching, 1380 patients from each group were included for further analysis. Overall, there was no significant difference in the mean operating time or SFR between the two groups. However, the hospital stay and postoperative pain score were significantly in favour of SMP (both P < 0.001). The tubeless rate was significantly higher in the SMP group (72.6% vs 57.8%, P < 0.001). Postoperative fever was much more common in the Miniperc group (12.0% vs 8.4%, P = 0.002). When the patients were further classified into three subgroups based on stones diameters (2-3, 3-4, and >4 cm). The advantages of SMP were most obvious in the 2-3 cm stone group and diminished as the size of the stone increased, with longer operating time in the latter two subgroups. Compared with Miniperc, the SFR of SMP was comparable for 3-4 cm stones, but lower for >4 cm stones. There was no statistical difference in blood transfusions and renal embolisations between the two groups. CONCLUSIONS: Our data showed that SMP is an ideal treatment option for stones of <4 cm and is more efficacious for stones of 2-3 cm, with lesser postoperative fever, blood loss, and pain compared to Miniperc. SMP was less effective for stones of >4 cm, with a prolonged operating time.

[Inhibitory effect of 3-bromopyruvate on the proliferation, migration and invasive ability of prostate cancer PC-3 cells].

OBJECTIVE: To observe the effects of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) on the proliferation, migration and invasive ability of prostate cancer PC-3 cells in vitro and explore the underlying mechanisms. METHODS: We cultured prostate cancer PC-3 cells in vitro and treated them with 3-BrPA at different concentrations for 24, 48 and 72 hours. Then we observed the morphological changes of the PC-3 cells under the inverted microscope. We also detected the effects of different concentrations of 3-BrPA on the proliferation, migration and invasive ability of the cells by MTT, wound-scratch and Transwell assays and determined the protein expressions of glucose transporter-1 (GLUT1), matrix metalloproteinase-14 (MMP-14), MMP-9 and MMP-2 in the PC-3 cells by Western blot. RESULTS: More significant changes were observed in the morphology of the PC-3 cells with increased concentrations of 3-BrPA. MTT assay showed that the inhibition rate of the proliferation of the PC-3 cells was remarkably increased in a concentration- and time-dependent manner (P<0.01). Wound-scratch and Transwell assays exhibited significant decreases in the scratch healing rate and number of invasive cells after 24 hours of intervention with 3-BrPA at 25, 50 and 100 µmol/L, even more significant after treated for 48 hours at the concentrations of 50 and 100 µmol/L (P<0.01). The expressions of the GLUT1, MMP-14, MMP-9 and MMP-2 proteins were markedly down-regulated after 3-BrPA intervention in comparison with those in the control group (P<0.01). CONCLUSIONS: The glycolysis inhibitor 3-BrPA reduces the proliferation, migration and invasive ability of prostate cancer PC-3 cells by down-regulating the expressions of the related proteins GLUT1, MMP-14, MMP-9 and MMP-2.

miR-124 exhibits antiproliferative and antiaggressive effects on prostate cancer cells through PACE4 pathway.

INTRODUCTION: PACE4 plays an important role in prostate cancer (PCa) proliferation and aggression, which might provide a useful target against prostate cancer. In this study, we had strived to find some key miRNAs to decrease malignancy and invasiveness of PCa through regulating PACE4 expression. METHODS: Clinically pathological analysis of immunohistochemistry/in situ hybridization was carried out to detect the relationship between PACE4 expression/miRNAs and the malignancy of prostate mass. Prostate cell lines (DU145, C4-2, and BPH-1) were cultured for growth curve, immunocytochemistry analysis, colony formation, Matrigel invasion, and transcriptional/translational expression assay of PACE4-related signaling molecules for confirming the relationship. MiRNAs targeting PACE4 were predicted, validated and further-corroborated using bio-software, real-time PCR, luciferase reporter assay and transfection of miRNA mimics and inhibitor. RESULTS: It was suggested that PACE4 might reflect the pathological malignancy of prostate lesion from pathology analysis. Moreover, DU145 cells, the highest PACE4-level and related TF expression indicated of the strongest malignancy and invasiveness. It was significantly found that miR-124 was presented with the biggest odd to target PACE4-3'UTR, the capability of decreasing PACE expression and slowing down cell growth and cell invasion. CONCLUSIONS: It was clear that PACE4 level was closely associated with malignancy and invasiveness of PCa in vivo or in vitro MiR-124, played a crucial role inhibiting PACE4 transcription thus exhibiting obvious effects of antiproliferation and antiaggression of PCa.

Nomograms for predicting clinically significant prostate cancer in men with PI-RADS-3 biparametric magnetic resonance imaging.

This study aimed to construct nomograms for predicting the likelihood of clinically significant prostate cancer (csPCa) in patients with lesions rated as Prostate Imaging Reporting and Data System (PI-RADS) 3 on biparametric magnetic resonance imaging (bpMRI). We retrospectively analyzed a cohort of 457 patients from the Peking Union Medical College Hospital (January 2017-July 2021) to develop the model and externally validated it with a cohort of 238 patients from the Second Hospital of Tianjin Medical University (September 2017-September 2021). Univariate and multivariate logistic regression analyses identified significant predictors of csPCa, defined by tumor volumes ≥ 0.5 cm3, Gleason score ≥ 7, or presence of extracapsular extension. Diagnostic performance for the peripheral zone (PZ) and transitional zone (TZ) was compared using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Through univariate and multivariate logistic regression analyses, we identified age, prostate-specific antigen (PSA), and prostate volume (PV) as predictors of csPCa for the PZ, and age, serum-free to total PSA ratio (f/t PSA), and PSA density (PSAD) for the TZ. The nomograms demonstrated robust discriminative ability, with an area under the ROC curve (AUC) of 0.819 for PZ and 0.804 for TZ. The external validation corroborated the model's high predictive accuracy (AUC of 0.831 for PZ and 0.773 for TZ). Calibration curves indicated excellent agreement between predicted and observed outcomes, and DCA underscored the nomogram's clinical utility for both PZ and TZ. Overall, the nomograms offer high predictive accuracy for csPCa at initial biopsy, potentially reducing unnecessary biopsies in clinical settings.

Multiple databases analyzed the prognosis prediction of renin secretion pathway-related genes in renal clear cell carcinoma and immunotherapy.

Background: Clear cell renal cell carcinoma (ccRCC) is a malignant kidney tumour and its progression is associated with the renin secretion pathway, so this study aimed to develop a prognostic model based on renin secretion pathway-related genes. Methods: First, 453 renin secretion pathway-related genes were acquired [|log fold change (FC)| >1.5, false discovery rate (FDR) <0.05] from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The data were combined and further screened for 188 genes associated with ccRCC prognosis (P<0.05) by univariate independent prognostic analysis. These genes were subjected to least absolute shrinkage and selection operator regression to identify potential prognostic genes to construct the prognostic model. The stability of the model was externally validated. Combined risk scores and clinical information were used to create nomograms to accurately reflect patient survival. The model-related genes were further mined for subsequent analysis. Results: A prognostic model of six renin secretion pathway genes (IGFBP3, PLAUR, CHKB-CPT1B, HOXA13, CDH13, and CDC20) was developed. Its reliability in predicting disease prognosis was confirmed by survival analysis, receiver operating characteristic (ROC) curve analysis and a risk curve. The nomogram and calibration curve showed good accuracy. The immune-related analyses revealed that the low-risk group would benefit more from immunotherapy. Conclusions: The prognostic model of ccRCC based on six renin secretion pathway-related genes can be used to guide the precise treatment of ccRCC patients.

Multiomics combined with single-cell analysis shows that mitophagy-related genes could accurately predict the prognosis of patients with clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is a heterogeneous tumor that accounts for a large proportion of kidney cancer, It is prone to recurrence and metastasis, and has a high mortality rate. Although mitophagy is important for metastasis and the recurrence of various tumors, its effect on renal clear cell carcinoma is poorly understood. Methods: Mitophagy-related genes were obtained through the GeneCards database. We normalised the data from different sources by removing the batch effect. Next, we conducted a preliminary screening of mitophagy-related genes and obtained prognosis-related genes from differentially expressed genes. We constructed a prognostic model using least absolute shrinkage and selection operator (LASSO) regression with data from The Cancer Genome Atlas (TCGA) and GSE29609 datasets and validated it internally. International Cancer Genome Consortium (ICGC) and E-MTAB-1980 cohorts also provided double external validation. In addition, we combined multi-omics and single-cell data to comprehensively analyse mitophagy-related gene model signature (MRGMS). Combined with the mitophagy-related gene model (MRGM) score, we constructed a nomogram. Finally, we performed pathway enrichment analysis using a variety of methods. Results: Multiomics and single-cell data analysis showed that the MRGMS is important for patients with ccRCC and is expected to become a new biomarker. The construction of a nomogram was conducive to accurately predicting patient survival. Conclusions: Mitophagy-related genes are important for predicting the prognosis of ccRCC and are conducive to the development of more personalised treatment plans for patients.

Untargeted metabolomics reveals that declined PE and PC in obesity may be associated with prostate hyperplasia.

BACKGROUND: Recent studies have shown that obesity may contribute to the pathogenesis of benign prostatic hyperplasia (BPH). However, the mechanism of this pathogenesis is not fully understood. METHODS: A prospective case-control study was conducted with 30 obese and 30 nonobese patients with BPH. Prostate tissues were collected and analyzed using ultra performance liquid chromatography ion mobility coupled with quadrupole time-of-flight mass spectrometry (UPLC-IMS-Q-TOF). RESULTS: A total of 17 differential metabolites (3 upregulated and 14 downregulated) were identified between the obese and nonobese patients with BPH. Topological pathway analysis indicated that glycerophospholipid (GP) metabolism was the most important metabolic pathway involved in BPH pathogenesis. Seven metabolites were enriched in the GP metabolic pathway. lysoPC (P16:0/0:0), PE (20:0/20:0), PE (24:1(15Z)/18:0), PC (24:1(15Z)/14:0), PC (15:0/24:0), PE (24:0/18:0), and PC (16:0/18:3(9Z,12Z,15Z)) were all significantly downregulated in the obesity group, and the area under the curve (AUC) of LysoPC (P-16:0/0/0:0) was 0.9922. The inclusion of the seven differential metabolites in a joint prediction model had an AUC of 0.9956. Thus, both LysoPC (P-16:0/0/0:0) alone and the joint prediction model demonstrated good predictive ability for obesity-induced BPH mechanisms. CONCLUSIONS: In conclusion, obese patients with BPH had a unique metabolic profile, and alterations in PE and PC in these patients be associated with the development and progression of BPH.

Long noncoding RNA GPRC5D-AS1 in renal cell carcinoma: a molecular mechanism study.

Background: Clear cell renal cell carcinoma (RCC) is the most common subtype of RCC. Although targeted therapy can provide superior treatment outcomes, it is prone to drug resistance, and individual responses to immunotherapy vary greatly. Therefore, finding new diagnostic and therapeutic targets for RCC is of considerable importance. Long noncoding RNA (lncRNA) GPRC5D-AS1 can serve as a biomarker in clinical applications and the prognosis of lung squamous cell carcinoma. However, the specific mechanism of action of lncRNA GPRC5D-AS1 in RCC has not yet been clarified. Therefore, this paper explores the expression of lncRNA GPRC5D-AS1 in the renal cancer cell line 786-0, and conducts a preliminary study of its molecular mechanism. Selecting nude mice for tumor experiments is because of the high genomic and physiological similarity between mice and humans. Conducting tumor research on mice allows for better control of experimental conditions, aiding researchers in more accurately observing and analysing tumor characteristics and responses. Methods: Small interfering RNA (siRNA) and plasmid cloning DNA (pcDNA) 3.1 were used to transfect renal cancer cell line 786-0 to silence and overexpress the lncRNA GPRC5D-AS1 gene. Quantitative real-time fluorescence polymerase chain reaction was used to detect the difference in lncRNA GPRC5D-AS1 expression in blank control group, negative control group, siGPRC5D-AS1 group and oeGPRC5D-AS1 group. The effects of silence and overexpression of lncRNA GPRC5D-AS11 on the proliferation of 786-0 cells were detected in cell colony formation experiments; the changes in the migration and invasion of 786-0 cells were detected via cell scratch assay and transwell assay, respectively; the differences in tumor growth between groups were determined via tumorigenesis experiments in nude mice; and the expression of proliferation-related protein [ß-catenin, Ki67 and proliferating cell nuclear antigen (PCNA)] and invasion-related protein (N-cadherin and E-cadherin) were detected via Western blotting. Results: Compared with blank control group and negative control group, the siGPRC5D-AS1 group showed a significant decrease in the relative expression of lncRNA GPRC5D-AS1 (P<0.05), a significant increase in the number of proliferating cells and migrating cells (P<0.05), a significant increase in the tumor volume of nude mice (P<0.05), a significant increase in ß-catenin, Ki67, PCNA and N-cadherin protein expression (P<0.05), and a significant decrease in E-cadherin protein expression (P<0.05); conversely, these results were opposite for the eGPRC5D-AS1 group. Conclusions: Silencing the expression of lncRNA GPRC5D-AS1 can enhance the proliferation, invasion, and migration ability of renal cancer cell line 786-0, which can be weakened by the overexpression of lncRNA GPRC5D-AS1.

[980 nm diode laser vaporization for benign prostatic hyperplasia].

OBJECTIVE: To explore the efficacy and safety of 980 nm diode laser vaporization in the treatment of benign prostatic hyperplasia (BPH). METHODS: We treated 92 BPH patients by 980 nm diode laser vaporization. The patients were aged 65 - 89 years, with a mean prostate volume of (50.1 +/- 13.0) ml. We analyzed and compared the mean operation time, intra-operative blood loss, postoperative complications, international prostate symptom score (IPSS), quality of life (QOL) score, maximum urine flow rate (Qmax), and post void residual (PVR) before and after surgery. RESULTS: Operations were successful in all the 92 cases, with an average operation time of (70.2 +/- 16.9) min, very little blood loss and no blood transfusion. The transurethral catheter indwelling time was 2 -5 (2.4 +/- 0.3) days. The patients were followed up for 1 to 3 months, which revealed a significant reduction in IPPS (P < 0.01) and improvement in Qmax and PVR (P < 0.01) as compared with preoperation. No severe complications were reported, including urinary incontinence and bladder irritation symptoms. None of the patients complained of impaired erectile function. CONCLUSION: Transurethral 980 nm diode laser vaporization is a safe and effective treatment for BPH.

LC-MS-based untargeted metabolomics reveals the mechanism underlying prostate damage in a type 2 diabetes mouse model.

Type 2 diabetes mellitus (T2DM) can cause prostate damage and affect male reproductive function, but the underlying mechanisms are not completely understood. In this study, we used liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics to identify endogenous metabolites in the prostate of a T2DM mouse model. The selected endogenous metabolites were then subjected to bioinformatics analysis and metabolic pathway studies to understand their role in the development of T2DM-induced prostate damage. We used male homozygous BTBR ob/ob mice (n = 12) and BTBR WT mice (n = 11) in this study. We monitored changes in blood glucose, body weight, prostate weight, and prostate index, as well as performed hematoxylin and eosin (H&E) staining and observed that the prostate of the BTBR ob/ob was damaged. We then used ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) for metabolomics analysis. The stability of the model was validated using principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). Using variable importance in projection (VIP) > 1, false discovery rate (FDR) < 0.05, and coefficient of variation (CV) < 30 as criteria, a total of 149 differential metabolites (62 upregulated and 87 downregulated) were identified between the prostates of the two groups of mice. Topological pathway analysis showed that these differential metabolites were mainly involved in sphingolipid (SP) and glycerophospholipid (GP) metabolism. In conclusion, our study not only emphasizes the damage caused by T2DM to the prostate but also provides new insights into the potential mechanisms of T2DM-induced male reproductive dysfunction.

Genes associated with inflammation for prognosis prediction for clear cell renal cell carcinoma: a multi-database analysis.

Background: Clear cell renal cell carcinoma (ccRCC) is the largest subtype of kidney tumour, with inflammatory responses characterising all stages of the tumour. Establishing the relationship between the genes related to inflammatory responses and ccRCC may help the diagnosis and treatment of patients with ccRCC. Methods: First, we obtained the data for this study from a public database. After differential analysis and Cox regression analysis, we obtained the genes for the establishment of a prognostic model for ccRCC. As we used data from multiple databases, we standardized all the data using the surrogate variable analysis (SVA) package to make the data from different sources comparable. Next, we used a least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model of genes related to inflammation. The data used for modelling and internal validation came from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) series (GSE29609) databases. ccRCC data from the International Cancer Genome Consortium (ICGC) database were used for external validation. Tumour data from the E-MTAB-1980 cohort were used for external validation. The GSE40453 and GSE53757 datasets were used to verify the differential expression of inflammation-related gene model signatures (IRGMS). The immunohistochemistry of IRGMS was queried through the Human Protein Atlas (HPA) database. After the adequate validation of the IRGM, we further explored its application by constructing nomograms, pathway enrichment analysis, immunocorrelation analysis, drug susceptibility analysis, and subtype identification. Results: The IRGM can robustly predict the prognosis of samples from patients with ccRCC from different databases. The verification results show that nomogram can accurately predict the survival rate of patients. Pathway enrichment analysis showed that patients in the high-risk (HR) group were associated with a variety of tumorigenesis biological processes. Immune-related analysis and drug susceptibility analysis suggested that patients with higher IRGM scores had more treatment options. Conclusions: The IRGMS can effectively predict the prognosis of ccRCC. Patients with higher IRGM scores may be better candidates for treatment with immune checkpoint inhibitors and have more chemotherapy options.

Identification of Bladder Cancer Subtypes Based on Necroptosis-Related Genes, Construction of a Prognostic Model.

Background: Necroptosis is associated with the development of many tumors but in bladder cancer the tumor microenvironment (TME) and prognosis associated with necroptosis is unclear. Methods: We classified patients into different necroptosis subtypes by the expression level of NRGS (necroptosis-related genes) and analyzed the relationship between necroptosis subtypes of bladder cancer and TME, then extracted differentially expressed genes (DEGS) of necroptosis subtypes, classified patients into different gene subtypes according to DEGS, and performed univariate COX analysis on DEGS to obtain prognosis-related DEGS. All patients included in the analysis were randomized into the Train and Test groups in a 1:1 ratio, and the prognostic model was obtained using the LASSO algorithm and multivariate COX analysis with the Train group as the sample, and external validation of the model was conducted using the GSE32894. Results: Two necroptosis subtypes and three gene subtypes were obtained by clustering analysis and the prognosis-related DEGS was subjected to the LASSO algorithm and multivariate COX analysis to determine six predictors to construct the prognostic model using the formula: riskScore = CERCAM × 0.0035 + POLR1H × -0.0294 + KCNJ15 × -0.0172 + GSDMB × -0.0109 + EHBP1 × 0.0295 + TRIM38 × -0.0300. The results of the survival curve, roc curve, and risk curve proved the reliability of the prognostic model by validating the model with the test group and the results of the calibration chart of the Nomogram applicable to the clinic also showed its good accuracy. Necroptosis subtype A with high immune infiltration had a higher risk score than necroptosis subtype B, gene subtype B with low immune infiltration had a lower risk score than gene subtypes A and C, CSC index was negatively correlated with the risk score and drug sensitivity prediction showed that commonly used chemotherapeutic agents were highly sensitive to the high-risk group. Conclusion: Our analysis of NRGS in bladder cancer reveals their potential role in TME, immunity, and prognosis. These findings may improve our understanding of necroptosis in bladder cancer and provide some reference for predicting prognosis and developing immunotherapies.

Cuproptosis-related lncRNA: Prediction of prognosis and subtype determination in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma, accounting for approximately 70% of all RCC cases. Cuproptosis, a novel mechanism of cell death, may be a potential target for intervention in tumor development. Methods: Cuproptosis-related prognostic lncRNAs were identified by co-expression analysis and univariable Cox regression. Five lncRNA profiles were obtained by LASSO regression analysis, and a model with high accuracy was constructed to assess the prognosis of ccRCC patients based on these cuproptosis-related lncRNAs. Survival analysis and time-dependent ROC curves were performed for the α and ß groups, and the results confirmed the high accuracy of the model in predicting the prognosis of ccRCC patients. Immunoassay, principal component analysis (PCA), and drug sensitivity analysis were also performed for different risk categories. Finally, we classified ccRCC patients into two different subtypes by consistent class clustering, and performed immune checkpoint activation, tumor microenvironment analysis, PCA, and drug sensitivity analysis for different subtypes. Results: We developed a prognostic model using five cuproptosis-associated lncRNAs, which was found to be highly accurate in predicting ccRCC patients' prognosis. Immunotherapy may be more beneficial to the hyper-risk category and the C2 subtype. Conclusion: The results of this study confirm that five cuproptosis-associated lncRNAs can be used as potential prognostic markers for ccRCC.

Identification of subtypes of clear cell renal cell carcinoma and construction of a prognostic model based on fatty acid metabolism genes.

Background: The effects of fatty acid metabolism in many tumors have been widely reported. Due to the diversity of lipid synthesis, uptake, and transformation in clear cell renal cell carcinoma (ccRCC) cells, many studies have shown that ccRCC is associated with fatty acid metabolism. The study aimed was to explore the impact of fatty acid metabolism genes on the prognosis and immunotherapy of ccRCC. Methods: Two subtypes were distinguished by unsupervised clustering analysis based on the expression of 309 fatty acid metabolism genes. A prognostic model was constructed by lasso algorithm and multivariate COX regression analysis using fatty acid metabolism genes as the signatures. The tumor microenvironment between subtypes and between risk groups was further analyzed. The International Cancer Genome Consortium cohort was used for external validation of the model. Results: The analysis showed that subtype B had a poorer prognosis and a higher degree of immune infiltration. The high-risk group had a poorer prognosis and higher tumor microenvironment scores. The nomogram could accurately predict patient survival. Conclusion: Fatty acid metabolism may affect the prognosis and immune infiltration of patients with ccRCC. The analysis was performed to understand the potential role of fatty acid metabolism genes in the immune infiltration and prognosis of patients. These findings have implications for individualized treatment, prognosis, and immunization for patients with ccRCC.