Globally, prostate cancer remains a leading cause of mortality and morbidity despite advances in treatment. Research on prostate cancer has primarily focused on the malignant epithelium, but the tumor microenvironment has recently been recognized as an important factor in the progression of prostate cancer. Cancer-associated fibroblasts (CAFs) play an important role in prostate cancer progression among multiple cell types in the tumor microenvironment. In order to develop new treatments and identify predictive and prognostic biomarkers for CAFs, further research is needed to understand the mechanism of action of prostate cancer and CAF. In this work, we performed the single-cell RNA sequence analysis to obtain the biomarkers for CAFs, and ten genes were finally regarded as the marker genes for CAFs. Based on the ssGSEA algorithm, the prostate cancer cohort was divided into low- and high-CAFs groups. Further analysis revealed that the CAFs-score is associated with many immune-related cells and immune-related pathways. In addition, between the low- and high-CAFs tissues, a total of 127 hub genes were discovered, which is specific in CAFs. After constructing the prognostic prediction model, SLPI, VSIG2, CENPF, SLC7A1, SMC4, and ITPR2 were finally regarded as the key genes in the prognosis of patients with prostate cancer. Each patient was assigned with the risk score as follows: SLPI* 0.000584811158157081 + VSIG2 * -0.01190627068889 + CENPF * -0.317826812875334 + SLC7A1 * -0.0410213995358753 + SMC4 * 0.202544454923637 + ITPR2 * -0.0824652047622673 + TOP2A * 0.140312081524807 + OR51E2 * -0.00136602095885459. The GSVA revealed the biological features of CAFs, many cancer-related pathways, such as the adipocytokine signaling pathway, ERBB signaling pathway, GnRH signaling pathway, insulin signaling pathway, mTOR signaling pathway and PPAR signaling pathway are closely associated with CAFs. As a result of these observations, similar transcriptomics may be involved in the transition from normal fibroblasts to CAFs in adjacent tissues. As one of the biomarkers for CAFs, CENPF can promote the proliferation ability of prostate cancer cells. The overexpress of CENPF could promote the proliferation ability of prostate cancer cells. In conclusion, we discuss the potential prognostic and therapeutic value of CAF-dependent pathways in prostate cancer.

Introduction Urologic malignancies are the major causes of morbidity and mortality in men over 40 years old, accounting for more than 20% of all malignant tumors. Several meta-analyses are shown that statin exposure can reduce the morbidity and mortality of various urologic cancers. The adjuvant roles of statin in tumor prevention and anti-tumor activity are now being gradually recognized and have gained attention. Nevertheless, to date, multiple clinical studies and meta-analyses found inconsistent results of their anti-cancer effects. This study aims to evaluate the credibility of the published systematic reviews and meta-analyses that assessed the effects of statin exposure for the incidence and mortality of urologic cancers through an umbrella review. Methods and analysis The guidance of overviews of systematic reviews reported in the Cochrane Handbook for Systematic Reviews of interventions will be followed while performing and reporting this umbrella review. This project was registered in PROSPERO with the registration number of CRD42020208854. PubMed, Embase and Cochrane Library will be searched for systematic reviews to identify and appraise systematic reviews or meta-analyses of interventional and observational studies examining statin use and the risks of urologic cancer incidence and mortality without language restriction. The search will be carried out on 10 February 2022. Systematic reviews based on qualitative, quantitative or mixed-methods studies will be involved and critically evaluated by two authors using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2, an updated version of AMSTAR) tool. We will determine the level of evidence using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) tool. The summary effect estimates will be calculated using random-effects models. Between- study heterogeneity will be assessed using the I2 statistic. Furthermore, we will also assess the evidence of excess significance bias and evidence of small study effects. Ethics and dissemination Ethics approval is not required as we will search and gather data based on the published systematic reviews and meta-analyses. We plan to publish the results of this umbrella review in a peer-reviewed journal and will be presented at a urological disease conference. All the relevant additional data will also be uploaded to the online open access databases. PROSPERO registration number CRD42020208854.

Renal cell carcinoma (RCC) is one of the leading causes of death in men. Messenger ribonucleic acid (mRNA) vaccines may be an attractive means to achieve satisfactory results. Cancer immunotherapy is a promising cancer treatment strategy. However, immunotherapy is not widely used in renal cell carcinoma, as only a few patients show a positive response. The present study aimed to identify potential antigens associated with renal cell carcinoma to develop an anti-renal cell carcinoma mRNA vaccine. Moreover, the immune subtypes of renal cell carcinoma cells were determined. The Cancer Genome Atlas (TCGA) analysis revealed gene expression profiles and clinical information. Antigen-presenting cells infiltrated the immune system using Tumor Immune Estimation Resource (TIMER) tool (http://timer.cistrome.org/). GDSC (Genomics of Drug Sensitivity in Cancer) database were used to estimate drug sensitivity. The 13 immune-related genes discovery could be targets for immunotherapy in renal cell carcinoma patients, as they were associated with a better prognosis and a higher level of antigen-presenting cells. These immune subtypes have significant relationships with immunological checkpoints, immunogenic cell death regulators, and RCC prognostic variables. Furthermore, DBH-AS1 was identified as a potential antigen for developing an mRNA vaccine. The CCK8 assay demonstrated that the proliferative capacity of 786-O and Caki-1 cells overexpressing DBH-AS1 was higher than in the control group. In addition, transwell assay revealed that 786-O and Caki-1 cells overexpressing DBH-AS1 showed higher invasion capacity compared with control. This study provides a theoretical basis for the development of mRNA vaccines. Our findings suggest that DBH-AS1 could be potential antigens for developing RCC mRNA vaccines.

Background: Accumulating evidence suggests that traditional Chinese medicine (TCM) has significant effects on reducing 24-h urinary protein (24-h UPRO) and improves renal function indices. The current level of evidence-based medicine is still not enough due to the limitation of clinical center size and sample size.Objective: We aimed to update the current evidence on the efficacy of TCM in the treatment of diabetic kidney disease (DKD).Methods: PubMed, Embase, the Cochrane Library, and SinoMed were searched to identify randomized controlled trials (RCTs) comparing the clinical efficacy of TCM combined with Western medicine with that of Western medicine alone for the treatment of DKD. The main outcome measure was 24-h UPRO. The secondary outcomes were serum creatinine (Scr), blood urea nitrogen (BUN), glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG). Meta-analyses were performed using random-effects models. The revised Cochrane risk-of-bias tool was used to assess the risk of bias.Results: A total of 44 RCTs with 3,730 participants were included. The summary estimates showed that compared with Western medicine alone, TCM combined with Western medicine significantly improved 24-h UPRO [standardized mean difference (SMD) −1.10, 95% confidence interval (CI) −1.45 to −0.74]. Moreover, TCM combined with Western medicine significantly reduced the levels of other renal function indices, including Scr (SMD −1.25, 95% CI: −1.69 to −0.81) and BUN (SMD −0.75, 95% CI: −1.10 to −0.40). TCM combined with Western medicine also showed greater benefits in reducing the levels of FBG (SMD −0.31, 95% CI: −0.47 to −0.15) and HbA1c (SMD −0.62, 95% CI: −0.89 to −0.36) in patients with DKD. In addition, superior effects on the lipid profile were noted in the TCM combined with Western medicine group in terms of TG (SMD −1.17, 95% CI: −1.76 to −0.59) and TC (SMD −0.95, 95% CI: −1.43 to −0.47). The risk of bias could have resulted from selective reports, unclear randomization methods, unblinded assignments, and some missing data.Conclusion: The results of this meta-analysis suggest that TCM combined with Western medicine has significant effects on reducing 24-h UPRO and improves renal function indices and lipid profiles compared with Western medicine alone for DKD. However, the results should be interpreted with caution due to the risk of bias of the included trials.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=213199], identifier [CRD: 42020213199].

Benign prostate hyperplasia (BPH) is one of the well-known urological neoplasms common in males with an increasing number of associated deaths in aging males. It causes uncomfortable urinary symptoms, including urine flow blockage, and may cause bladder, urinary tract or kidney problems. The histopathological and clinical knowledge regarding BPH is limited. In the present study, an in silico approach was applied that uses genome-scale microarray expression data to discover a wide range of protein-protein interactions in addition to focusing on specific genes responsible for BPH to develop prognostic biomarkers. Various genes that were differentially expressed in BPH were identified. Gene and functional annotation clusters were determined and an interaction analysis with disease phenotypes of BPH was performed, as well as an RNA tissue specificity analysis. Furthermore, a molecular docking study of certain short-listed gene biomarkers, namely anterior gradient 2 (AGR2; PDB ID: 2LNT), steroid 5α-reductase 2 (PDB ID: 6OQX), zinc finger protein 3 (PDB ID: 5T00) and collagen type XII α1 chain (PDB ID: 1U5M), was performed in order to identify alternative Chinese herbal agents for the treatment of BPH. Data from the present study revealed that AGR2 receptor (PDB ID: 2LNT) and berberine (Huang Bo) form the most stable complex and therefore may be assessed in further pharmacological studies for the treatment of BPH.

Chinese herbal medicine (CHM), which includes herbal slices and proprietary products, is widely used in China. Shenqi Dihuang (SQDH) is a traditional Chinese medicine (TCM) formula with ingredients that affect tumor growth. Despite recent advances in prognosis, patients with renal cell carcinoma (RCC) cannot currently receive curative treatment. The present study aimed to explore the potential target genes closely associated with SQDH. The gene expression data for SQDH and RCC were obtained from the TCMSP and TCGA databases. The SQDH-based prognostic prediction model reveals a strong correlation between RCC and SQDH. In addition, the immune cell infiltration analysis indicated that SQDH might be associated with the immune response of RCC patients. Based on this, we successfully built the prognostic prediction model using SQDH-related genes. The results demonstrated that CCND1 and NR3C2 are closely associated with the prognosis of RCC patients. Finally, the pathways enrichment analysis revealed that response to oxidative stress, cyclin binding, programmed cell death, and immune response are the most enriched pathways in CCND1. Furthermore, transcription regulator activity, regulation of cell population proliferation, and cyclin binding are closely associated with the NR3C2.

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