Rationale for immune checkpoint inhibitors plus targeted therapy for advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is a frequent urological malignancy characterized by a high rate of metastasis and lethality. The treatment strategy for advanced RCC has moved through multiple iterations over the past three decades. Initially, cytokine treatment was the only systemic treatment option for patients with RCC. With the development of medicine, antiangiogenic agents targeting vascular endothelial growth factor and mammalian target of rapamycin and immunotherapy, immune checkpoint inhibitors (ICIs) have emerged and received several achievements in the therapeutics of advanced RCC. However, ICIs have still not brought completely satisfactory results due to drug resistance and undesirable side effects. For the past years, the interests form researchers have been attracted by the combination of ICIs and targeted therapy for advanced RCC and the angiogenesis and immunogenic tumor microenvironmental variations in RCC. Therefore, we emphasize the potential principle and the clinical progress of ICIs combined with targeted treatment of advanced RCC, and summarize the future direction.

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.

Identification and verification of anoikis-related gene markers to predict the prognosis of patients with bladder cancer and assist in the diagnosis and treatment of bladder cancer.

Background: The recurrence and mortality rates of bladder cancer are extremely high, and its diagnosis and treatment are global concerns. The mechanism of anoikis is closely related to tumor metastasis. Methods: First, we obtained all the data needed for this study from a public database through a formal operational process. The data were then analyzed by bioinformatics technology. Through the limma package, we screened and obtained 313 anoikis-related genes [false discovery rate (FDR) <0.05, |log fold change (FC) | >0.585]. Then, through univariate independent prognostic analysis, we further screened 146 genes (P<0.05) related to the prognosis of bladder cancer from 313 differential genes. These 146 prognostically relevant differential genes were used for least absolute shrinkage and selection operator (LASSO) regression for further screening to obtain model-related genes and output model formulas. Through the nomogram, we can calculate the survival rate of patients more accurately. The accuracy of the nomogram was also confirmed by calibration curves, independent prognostic analysis, receiver operating characteristic (ROC) curves, decision curve analysis (DCA) curves. We then analysed the sensitivity of immunotherapy in bladder cancer patients with different risk scores via Tumor Immune Dysfunction and Exclusion (TIDE). Results: Through bioinformatics technology and public databases, a prognostic model including 9 anoikis-related genes (KLF12, INHBB, CASP6, TGFBR3, FASN, TPM1, OGT, RAC3, ID4) was obtained. Integrating risk scores with clinical information, we obtained a nomogram that can accurately predict patient survival. By querying the immunohistochemical results of the Human Protein Atlas database, two of the nine model-related genes (FASN, RAC3) have the value of further research and are expected to become new biomarkers to assist the diagnosis and treatment of bladder cancer. Through immune-related analysis, we found that patients in the low-risk group appeared to be more suitable for immunotherapy, while drug sensitivity analysis showed that bladder cancer patients in the high-risk group were more sensitive to common chemotherapy drugs. Conclusions: In this study, a prognostic model that can accurately predict the prognosis of patients with bladder cancer was constructed. FASN and RAC3 are expected to become a new biomarker for the diagnosis and treatment of bladder cancer.

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.

Comprehensive analysis of mitochondria-related genes indicates that PPP2R2B is a novel biomarker and promotes the progression of bladder cancer via Wnt signaling pathway.

Bladder cancer (BC) is the fourth and tenth most common malignancy in men and women worldwide, respectively. The complexity of the molecular biological mechanism behind BC is a major contributor to the lack of effective treatment management of the disease. The development and genesis of BC are influenced by mitochondrial retrograde control and mitochondria-nuclear cross-talk. However, the role of mitochondrial-related genes in BC remains unclear. In this study, we analyzed TCGA datasets and identified 752 DE-MRGs in BC samples, including 313 down-regulated MRGs and 439 up-regulated MRGs. Then, the results of machine-learning screened four critical diagnostic genes, including GLRX2, NMT1, PPP2R2B and TRAF3IP3. Moreover, we analyzed their prognostic value and confirmed that only PPP2R2B was associated with clinical prognosis of BC patients and Cox regression assays validated that PPP2R2B expression was a distinct predictor of overall survival in BC patients. Them, we performed RT-PCR and found that PPP2R2B expression was distinctly decreased in BC specimens and cell lines. Functional experiments revealed that overexpression of PPP2R2B distinctly suppressed the proliferation, migration and invasion of BC cells via Wnt signaling pathway. In summary, these research findings offer potential molecular markers for the diagnosis and prognosis of BC, with the discovery of PPP2R2B particularly holding significant biological and clinical significance. This study provides valuable clues for future in-depth investigations into the molecular mechanisms of BC, as well as the development of new diagnostic markers and therapeutic targets.

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.

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.

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.

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.

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.

Silencing miRNA-1297 suppresses the invasion and migration of prostate cancer cells via targeting modulation of PTEN and blocking of the AKT/ERK pathway.

Phosphatase and tensin homolog (PTEN) loss is a major contributing factor of prostate cancer (PC). miRNA-1297 was reported to serve role in various cancer types; however, the potential roles of miRNA-1297 in PC had not been investigated. In the present study, tumor and adjacent tissues were collected from patients with PC. The gene expression level of miRNA-1297 was measured via polymerase chain reaction. Results indicated that the miRNA-1297 was overexpressed in tumor tissues from PC patients and in PC cell lines. miRNA-1297 also contributed toward the progression of PC. PTEN was confirmed as the direct target of miRNA-1297 and bound with miRNA-1297 via four binding sites. The miRNA-1297 level was negatively associated with the PTEN level. Silencing miRNA-1297 or overexpression of PTEN significantly inhibited the cell migration and invasion. In addition, the AKT/ERK pathway was also inhibited following silencing of miRNA-1297 or overexpression of PTEN. Taken together, the results indicated that silencing miRNA-1297 exerted inhibitory effects on the invasion and migration of PC cells via modulating PTEN and blocking of the AKT/ERK pathway. The results of the present study provided a novel strategy for treatment of prostate cancer cells.

Lack of association between the risk of prostate cancer and vitamin D receptor Bsm I polymorphism: a meta-analysis of 27 published studies.

BACKGROUND: The association between vitamin D receptor gene Bsm I (rs1544410) polymorphism and prostate cancer (PCa) risk has been investigated by numerous previous studies, which yielded inconsistent results. We conducted this meta-analysis to derive a relatively precise description of this association. METHODS: All studies published up to December 2017 were identified via a systematic search of PubMed, Embase, and China National Knowledge Infrastructure databases. Pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated to describe the strength of the relationship between Bsm I and PCa risk. RESULTS: In this meta-analysis, 27 studies with 9,993 cases and 9,345 controls were included. The pooled results revealed that Bsm I polymorphism was not associated with PCa risk in the overall analysis. Moreover, no significant relationship was found in the subgroup analyses by ethnicities, genotyping methods, Hardy-Weinberg equilibrium status, and Gleason score. In the stratified analysis by the source of controls and clinical stages, controls of benign prostatic hyperplasia (BPH) seemed to be in the particular groups in which the association of PCa risk with Bsm I polymorphism was significant (Bb vs. bb: OR=0.643, 95% CI=0.436-0.949, p=0.026; BB/Bb vs. bb: OR=0.627, 95% CI=0.411-0.954, p=0.029; B vs. b: OR=0.715, 95% CI=0.530-0.965, p=0.029). CONCLUSION: Our results suggest that Bsm I polymorphism is weakly associated with PCa risk, and hence, it cannot be considered as a predictor of the occurrence and development of PCa in clinical practice. Future studies with a larger number of samples are needed to verify our results.

Vitamin D receptor Taq I polymorphism and the risk of prostate cancer: a meta-analysis.

Numerous previous studies reported the association of Vitamin D receptor gene Taq Ipolymorphism with prostate cancer risk, however these results were controversial. In order to provide a relatively comprehensive description of this relationship, we conducted this meta-analysis by searching PubMed, Embase, and China National Knowledge Infrastructure. Finally, 36 studies with 8,423 cases and 8,887 controls were included. Taq I polymorphism was found to marginally increase the prostate cancer risk in recessive genetic model (tt/Tt vs. TT: Odds Ratio (OR) = 0.89, 95% Confidence Interval (CI) = 0.80-1.00, p = 0.05) and allele genetic model (t vs. T allele: OR = 0.91, 95% CI = 0.84-0.99, p = 0.003) in the overall analysis. Subgroup analyses showed that significant increased risk was found in Asians in homozygote model (tt vs. TT: OR = 0.63, 95% CI = 0.41-0.95, p = 0.029) and allele genetic model (t vs. T: OR = 0.78, 95% CI = 0.67-0.90, p = 0.002), and in the subgroup of population-based controls in all the genetic models. These results suggest that Taq Ipolymorphism might be a risk factor of prostate cancer risk, especially in Asians. It could be considered as a promising target to predict the prostate cancer risk for clinical practice.

Association of Vitamin D receptor Fok I polymorphism with the risk of prostate cancer: a meta-analysis.

Several previous studies have been reported to examine the association between Vitamin D receptor (VDR) gene Fok I polymorphism and susceptibility to prostate cancer (PCa), however the results remain inconclusive. To provide a relatively comprehensive account of the association, we searched PubMed, Embase, CNKI, and Wanfang for eligible studies and carry out this meta-analysis. A total of 27 case-control studies with 10,486 cases and 10,400 controls were included. In the overall analysis, Fok I polymorphism was not significantly associated with the susceptibility to PCa. Subgroup analyses showed that significantly association was existed in Caucasian population, the subgroup of population-based controls and the stratified group with advanced tumor.These results indicate that the VDR Fok I polymorphism might be capable of causing PCa susceptibility and could be a promising target to forecast the PCa risk for clinical practice. However further well-designed epidemiologic studies are needed to confirm this conclusion.

Bioinformatics analysis of differentially expressed proteins in prostate cancer based on proteomics data.

We mined the literature for proteomics data to examine the occurrence and metastasis of prostate cancer (PCa) through a bioinformatics analysis. We divided the differentially expressed proteins (DEPs) into two groups: the group consisting of PCa and benign tissues (P&b) and the group presenting both high and low PCa metastatic tendencies (H&L). In the P&b group, we found 320 DEPs, 20 of which were reported more than three times, and DES was the most commonly reported. Among these DEPs, the expression levels of FGG, GSN, SERPINC1, TPM1, and TUBB4B have not yet been correlated with PCa. In the H&L group, we identified 353 DEPs, 13 of which were reported more than three times. Among these DEPs, MDH2 and MYH9 have not yet been correlated with PCa metastasis. We further confirmed that DES was differentially expressed between 30 cancer and 30 benign tissues. In addition, DEPs associated with protein transport, regulation of actin cytoskeleton, and the extracellular matrix (ECM)-receptor interaction pathway were prevalent in the H&L group and have not yet been studied in detail in this context. Proteins related to homeostasis, the wound-healing response, focal adhesions, and the complement and coagulation pathways were overrepresented in both groups. Our findings suggest that the repeatedly reported DEPs in the two groups may function as potential biomarkers for detecting PCa and predicting its aggressiveness. Furthermore, the implicated biological processes and signaling pathways may help elucidate the molecular mechanisms of PCa carcinogenesis and metastasis and provide new targets for clinical treatment.

Construction and analysis of protein-protein interaction networks based on proteomics data of prostate cancer.

Currently, using human prostate cancer (PCa) tissue samples to conduct proteomics research has generated a large amount of data; however, only a very small amount has been thoroughly investigated. In this study, we manually carried out the mining of the full text of proteomics literature that involved comparisons between PCa and normal or benign tissue and identified 41 differentially expressed proteins verified or reported more than 2 times from different research studies. We regarded these proteins as seed proteins to construct a protein-protein interaction (PPI) network. The extended network included one giant network, which consisted of 1,264 nodes connected via 1,744 edges, and 3 small separate components. The backbone network was then constructed, which was derived from key nodes and the subnetwork consisting of the shortest path between seed proteins. Topological analyses of these networks were conducted to identify proteins essential for the genesis of PCa. Solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4) had the highest closeness centrality located in the center of each network, and the highest betweenness centrality and largest degree in the backbone network. Tubulin, beta 2C (TUBB2C) had the largest degree in the giant network and subnetwork. In addition, using module analysis of the whole PPI network, we obtained a densely connected region. Functional annotation indicated that the Ras protein signal transduction biological process, mitogen-activated protein kinase (MAPK), neurotrophin and the gonadotropin-releasing hormone (GnRH) signaling pathway may play an important role in the genesis and development of PCa. Further investigation of the SLC2A4, TUBB2C proteins, and these biological processes and pathways may therefore provide a potential target for the diagnosis and treatment of PCa.

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.

[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.