Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.

Background: Published studies present conflicting data regarding the impact of Thrombospondin-1 (TSP-1) expression on prognosis of various cancers. We performed this meta-analysis to illustrate the preliminary predictive value of TSP-1. Methods: Twenty-four studies with a total of 2379 patients were included. A comprehensive literature search was performed by using PubMed, Cochrane Library, Web of Science, Embase, and hand searches were also conducted of relevant bibliographies. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for patient survival and disease recurrence were initially identified to explore relationships between TSP-1 expression and patient prognosis. Results: A total of 24 eligible studies were included in this meta-analysis. Our results showed that high level of TSP-1 was correlated significantly with poor overall survival (OS) (HR = 1.40, 95% CI: 1.17 ~ 1.68; P<0.001). However, high TSP-1 expression predicted no significant impact on progression-free survival (PFS)/ metastasis-free survival (MFS) (HR = 1.35, 95%CI: 0.87–2.10; P = 0.176) and disease-free survival (DFS)/ recurrence-free survival (RFS) (HR = 1.40, 95%CI: 0.77–2.53; P = 0.271). In addition, we performed subgroup analyses which showed that high TSP-1 expression predicted poor prognosis in breast cancer and gynecological cancer. Additionally, the relatively small number of studies on PFS/MFS and DFS/RFS is a limitation. The data extracted through Kaplan-Meier curves may not be accurate. Moreover, only English articles were included in this article, which may lead to deviations in the results. Conclusions: Our findings indicated high TSP-1 expression may act as a promising biomarker of poor prognosis in cancers, especially in breast cancer and gynecological cancer.

With the widespread use of PD‐1/PD‐L1 monoclonal antibodies (mAbs) in the treatment of multiple malignant tumors, they were also gradually applied to advanced renal cell carcinoma (aRCC). Nowadays, multiple PD‐1/PD‐L1 mAbs, such as nivolumab, avelumab, and pembrolizumab, have achieved considerable efficacy in clinical trials. However, due to the primary, adaptive, and acquired resistance to these mAbs, the efficacy of this immunotherapy is not satisfactory. Theories also vary as to why the difference in efficacy occurs. The alterations of PD‐L1 expression and the interference of cellular immunity may affect the efficacy. These mechanisms demand to be revealed to achieve a sustained and complete objective response in patients with aRCC. Tyrosine kinase inhibitors have been proven to have synergistic mechanisms with PD‐1/PD‐L1 mAb in the treatment of aRCC, and CTLA‐4 mAb has been shown to have a non‐redundant effect with PD‐1/PD‐L1 mAb to enhance efficacy. Although combinations with targeted agents or other checkpoint mAbs have yielded enhanced clinical outcomes in multiple clinical trials nowadays, the potential of PD‐1/PD‐L1 mAbs still has a large development space. More potential mechanisms that affect the efficacy demand to be developed and transformed into the clinical treatment of aRCC to search for possible combination regimens. We elucidate these mechanisms in RCC and present existing combination therapies applied in clinical trials. This may help physicians’ select treatment options for patients with refractory kidney cancer.

Metabolic reprogramming is one of the characteristics of clear cell renal cell carcinoma (ccRCC). Although some treatments associated with the metabolic reprogramming for ccRCC have been identified, remain still lacking. In this study, we identified the differentially expressed genes (DEGs) associated with clinical traits with a total of 965 samples via DEG analysis and weighted correlation network analysis (WGCNA), screened the prognostic metabolism-related genes, and constructed the risk score prognostic models. We took the intersection of DEGs with significant difference coexpression modules and received two groups of intersection genes that were connected with metabolism via functional enrichment analysis. Then we respectively screened prognostic metabolic-related genes from the genes of the two intersection groups and constructed the risk score prognostic models. Compared with the predicted effect of clinical grade and stage for ccRCC patients, finally, we selected the model constructed with genes of ABAT, ALDH6A1, CHDH, EPHX2, ETNK2, and FBP1. The risk scores of the prognostic model were significantly related to overall survival (OS) and could serve as an independent prognostic factor. The Kaplan-Meier analysis and ROC curves revealed that the model efficiently predicts prognosis in the TCGA-KIRC cohort and the validation cohort. Then we investigated the potential underlying mechanism and sensitive drugs between high- and low-risk groups. The six key genes were significantly linked with worse OS and were downregulated in ccRCC, we confirmed the results in clinical samples. These results demonstrated the efficacy and robustness of the risk score prognostic model, based on the characteristics of metabolic reprogramming in ccRCC, and the key genes used in constructing the model also could develop into targets of molecular therapy for ccRCC.

Background. Tumor cells with a hybrid metabolic state, in which glycolysis and oxidative phosphorylation (OXPHOS) can be used, usually have a strong ability to adapt to different stress environments due to their metabolic plasticity. However, few studies on tumor cells with this phenotype have been conducted in the field of renal cell carcinoma (RCC). Methods. The metabolic pathway (glycolysis, OXPHOS) related gene sets were obtained from the Molecular Signatures Database (V7.5.1). The gene expression matrix, clinical information, and mutation data were obtained by Perl programming language (5.32.0) mining, the Cancer Genome Atlas and International Cancer Genome Consortium database. Gene Set Enrichment Analysis (GSEA) software (4.0.3) was utilised to analyse glycolysis-related gene sets. Analysis of survival, immune infiltration, mutation, etc. was performed using the R programming language (4.1.0). Results. Eight genes that are highly associated with glycolysis and OXHPOS were used to construct the cox proportional hazards model, and risk scores were calculated based on this to predict the prognosis of clear cell RCC patients and to classify patients into risk groups. Gene Ontology, the Kyoto Encyclopaedia of Genes and Genomes, and GSEA were analysed according to the differential genes to investigate the signal pathways related to the hybrid metabolic state. Immunoinfiltration analysis revealed that CD8+T cells, M2 macrophages, etc., had significant differences in infiltration. In addition, the analysis of mutation data showed significant differences in the number of mutations of PBRM1, SETD2, and BAP1 between groups. Cell experiments demonstrated that the DLD gene expression was abnormally high in various tumor cells and is associated with the strong migration ability of RCC. Conclusions. We successfully constructed a risk score system based on glycolysis and OXPHOS-related genes to predict the prognosis of RCC patients. Bioinformatics analysis and cell experiments also revealed the effect of the hybrid metabolic activity on the migration ability and immune activity of RCC and the possible therapeutic targets for patients.

To assess the technical feasibility and outcomes of robotic-assisted partial nephrectomy (RPN) with sequential segmental renal artery (SRA) clamping for multiple ipsilateral renal tumors (MIRTs). From April 2016 to February 2018, consecutive eleven cases successfully underwent RPN with sequential SRA clamping under the guidance of dual-source computed tomography (DSCT). Ten cases had two lesions and two cases had three at the ipsilateral kidneys. The mean size and the mean R.E.N.A.L score for the dominant lesion of single case were 3.3 cm and 5.7, respectively. Twenty-two lesions (84.6%) had one target SRA and four (15.4%) had two target SRAs. Satisfactory ischemic areas were achieved by sequentially clamping two (81.8%) or three (18.2%) target SRAs with mean clamping time of 18.8 (15.0–27.0) min for single lesion, and the mean of total clamping time for single case was 37.5 (32.0–52.0) min. Only the complications of grade 1–2 were found and no positive surgical margin was discovered. The mean follow-up time was 5.4 months and no local recurrence or metastasis was found. The mean postoperative eGFR was 71.2 ml/minute/1.73m2 that was only an insignificant reduction (9.3%) compared with the preoperative baseline. This novel nephron-sparing technique, RPN with sequential SRA clamping, represents a good alternative for selected patients with MIRTs. With the guidance of DSCT and skilled robotic experience, this technique is feasible and can maximize renal function preservation. Large-scale multicenter clinical studies are still needed to further prove these initial outcomes.