BACKGROUND/OBJECTIVES:We aimed to identify angiogenesis-related prognostic biomarkers and develop a radiogenomics model to predict overall survival (OS) in clear cell renal cell carcinoma (ccRCC), supporting risk stratification and potential therapeutic target discovery. METHODS:Bulk transcriptomes from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma cohort (TCGA-KIRC), seven Gene Expression Omnibus (GEO) microarrays, and a single-cell RNA sequencing (scRNA-seq) dataset were integrated to identify angiogenesis-related prognostic genes. Preoperative contrast-enhanced computed tomography (CT) images from The Cancer Imaging Archive Kidney Renal Clear Cell Carcinoma collection (TCIA-KIRC) were used for radiomics feature extraction, and a radiogenomics signature was constructed by linking radiomic features with transcriptomic risk patterns. Nine machine learning models were trained to predict OS; the best model was further evaluated in an independent external retrospective cohort. PDLIM1 (PDZ and LIM domain protein 1) was validated at the protein level, and conditioned medium from stable ccRCC cell lines was applied to human umbilical vein endothelial cells (HUVECs) for Matrigel tube formation assays. RESULTS:Five angiogenesis-related hub genes (PDLIM1, EMCN, ARPC1B, PLAT, and TIMP1) were identified. The extreme gradient boosting (XGBoost)-based radiogenomics model showed the best performance, with time-dependent concordance index (C-index) values of 0.880, 0.816, and 0.789 at 1, 3, and 5 years in the training set and 0.864, 0.758, and 0.736 in the internal validation set, respectively. In the external validation cohort, C-index values were 0.800, 0.726, and 0.703 at 1, 3, and 5 years. PDLIM1 protein was upregulated in ccRCC versus normal tissues. Functionally, PDLIM1 overexpression suppressed, whereas PDLIM1 knockdown promoted tube formation. CONCLUSIONS:This study developed and validated an angiogenesis-related radiogenomics model that accurately predicts OS in ccRCC patients and provides potential therapeutic targets for anti-angiogenic therapy.

This study aimed to systematically evaluate the operative and perioperative outcomes of transperitoneal laparoscopic adrenalectomy (TLA) and retroperitoneal laparoscopic adrenalectomy (RLA) for the treatment of adrenal tumors, aiming to clearly identify the advantages and disadvantages of each surgical approach. Databases, including PubMed, the Cochrane Library, Embase, Web of Science, and Scopus, were searched from their establishment to June 2025 for randomized controlled trials (RCTs) comparing the operative and perioperative outcomes of TLA and RLA. Meta-analysis was performed according to the PRISMA guidelines. Data on operative time, intraoperative blood loss, time to postoperative oral intake, time to postoperative ambulation, postoperative hospital stay, complication rate, conversion to open surgery rate, and postoperative pain score were extracted. Two reviewers independently screened the literature, extracted the data, and assessed the risk of bias. Meta-analysis was performed using RevMan 5.4 (The Nordic Cochrane Centre, Copenhagen, Denmark) and Stata 18 (StataCorp LP, College Station, TX, USA). Five studies were included, involving a total of 306 patients (143 in the TLA group and 163 in the RLA group). The results showed that compared with RLA, TLA had a longer time to postoperative oral intake (MD = 9.60, 95

Bladder cancer (BC) is one of the most common malignancies of the urinary system, and chemoresistance remains a major obstacle limiting the clinical efficacy of cisplatin-based chemotherapy. Elucidating the mechanisms underlying cisplatin resistance may facilitate the identification of potential therapeutic targets and ultimately improve patient outcomes. In this study, we found that Y-box binding protein 1 (YBX1) was upregulated in bladder cancer tissues with poor chemotherapeutic response as well as in cisplatin-resistant bladder cancer cell lines, where it promoted tumor cell proliferation and invasion. Functional assays demonstrated that depletion of YBX1 significantly enhanced cisplatin sensitivity in both in vitro and in vivo. Mechanistically, elevated YBX1 expression was associated with reduced ferroptosis sensitivity in cisplatin-resistant cells. Although YBX1 induced autophagy and was accompanied by a reduction in glutathione peroxidase 4 (GPX4) protein levels, the overall enhancement of intracellular antioxidant capacity in resistant cells may partially offset the increased susceptibility to ferroptosis caused by GPX4 degradation. Furthermore, we identified the transcription factor ELK1 as an upstream regulator that transcriptionally upregulates YBX1, while YBX1 may contribute to the cisplatin-resistant phenotype through activation of the p62-NRF2-associated antioxidant pathway. Collectively, these findings highlight a critical role of YBX1 in cisplatin resistance and suggest that targeting YBX1 may represent a promising strategy for overcoming cisplatin-based chemoresistance in bladder cancer.

Background: Although POLD1 exhibits oncogenic properties in multiple malignancies, its precise role and regulatory mechanisms in cisplatin resistance of bladder cancer (BC) remain elusive. This study aims to elucidate the functional involvement and upstream regulatory axis of POLD1 in BC chemoresistance. Methods: We evaluated the impact of POLD1 on chemoresistance and DNA damage repair (DDR) using public clinical databases and cisplatin-resistant cell lines, employing CCK-8, colony formation, flow cytometry, immunofluorescence, and comet assays. Protein interactions were examined via Co-IP, molecular docking, and truncation mutant analysis. ChIP-PCR and dual-luciferase reporter assays were utilized to identify the upstream transcription factor. In vivo functionality was further validated in a nude mouse xenograft model. Results: POLD1 was markedly upregulated in BC tissues and cisplatin-resistant BC cells, and its elevated expression was tightly associated with advanced tumor stage, high pathological grade, and poor patient prognosis. Functional experiments verified that POLD1 knockdown aggravated cisplatin-induced DNA damage and drastically sensitized BC cells to cisplatin in vitro, and attenuated tumor growth under cisplatin treatment in vivo, indicating that POLD1 is a key driver of cisplatin resistance. Mechanistically, POLD1 physically interacted with and activated ATM, thereby initiating homologous recombination (HR) repair signaling. Moreover, transcription factor MAZ directly bound the promoter region of POLD1 to transcriptionally upregulate its expression. Rescue experiments in vitro further validated that the MAZ-POLD1 axis facilitates cisplatin resistance by modulating the DDR pathway in BC. Conclusions: Therapeutic targeting of the POLD1-regulated DDR pathway holds great promise as an effective strategy to reverse acquired cisplatin resistance in BC.

To assess whether preoperative non-contrast CT-derived adiposity quantity and attenuation are independently associated with recurrence-free survival (RFS) after surgery for localized clear cell renal cell carcinoma (ccRCC). We performed a single-center retrospective cohort study of adults with pathologically confirmed ccRCC who underwent upfront partial or radical nephrectomy and had preoperative non-contrast abdominal CT within 30 days. A single mid-L3 axial slice was segmented for subcutaneous (SAT) and visceral adipose tissue (VAT) using predefined thresholds (SAT−190 to −30 HU; VAT−150 to−50 HU). Adiposity indices were normalized by height squared (SATI, VATI), and mean SAT/VAT attenuation (HU) was recorded. RFS was defined as time from surgery to first documented local/regional recurrence or distant metastasis. Multi-variable Cox models were adjusted for age, sex, chronic disease history, tumor diameter, surgery type, and WHO/ISUP grade; continuous predictors were standardized (per 1-SD). Incremental prognostic performance beyond the clinicopathologic base model was assessed using Harrell’s C-index. Among 598 patients, 151 (25.3

BackgroundG6PC has emerged as a prognostic biomarker and potential therapeutic target in cancer, but its role in renal cell carcinoma (RCC) remains unclear.MethodsWe analyzed G6PC expression using TCGA, GEO, and clinical data, with protein validation via HPA. Pathway enrichment, immune infiltration, and methylation analyses were performed. Prognostic value was assessed by Cox regression and Kaplan-Meier analysis. In vitro and in vivo experiments evaluated the effects of G6PC dysregulation. Transcriptome sequencing, ChIP-qPCR, and dual-luciferase reporter assays were used to identify upstream transcriptional regulators.ResultsG6PC was significantly downregulated in RCC and inversely correlated with TNM stage, grade, and immune infiltration. Hypomethylation of G6PC was observed. Enrichment analyses linked G6PC to BCR signaling and ECM-related pathways. Overexpression of G6PC inhibited RCC cell proliferation and migration. Mechanistically, FOXO1 was validated as a direct transcriptional regulator of G6PC, as demonstrated by enrichment of FOXO1 binding on the G6PC promoter (ChIP-qPCR) and promoter activation in dual-luciferase assays. Furthermore, G6PC exerted negative feedback on FOXO1 signaling, establishing a bidirectional regulatory loop.ConclusionsG6PC functions as a tumor suppressor in RCC and is directly transcriptionally activated by FOXO1, forming a FOXO1-G6PC axis that restrains RCC progression. This mechanistic insight highlights G6PC as a promising therapeutic and prognostic target.

ObjectivesTo evaluate real-world effectiveness and safety of adjuvant disitamab vedotin plus PD-1 blockade (ADC+ICI) versus gemcitabine/cisplatin (GC) in high-risk upper tract urothelial carcinoma after radical nephroureterectomy.Patients and methodsThis single-center, two-stage observational study enrolled 421 patients with study-defined high-risk upper tract urothelial carcinoma. Cohort A evaluated adjuvant GC versus surgery alone using propensity score matching. Cohort B compared adjuvant GC with ADC+ICI using overlap weighting, with ECOG performance status and three-level HER2 IHC category included in covariate adjustment. Overall survival (OS), conventional disease-free survival (DFS), non-intravesical progression-free survival (PFS), intravesical recurrence-free survival (IVRFS), safety, and exploratory HER2-stratified outcomes were assessed.ResultsIn Cohort A, adjuvant GC was associated with improved OS after matching. In Cohort B, 48 patients received GC and 53 received ADC+ICI. After overlap weighting, baseline covariates were well balanced. ADC+ICI was not associated with a significant OS improvement versus GC (HR 0.47, 95% CI 0.12–1.89; P = 0.287; FDR-adjusted P = 0.403). Directionally favorable associations were observed for conventional DFS (HR 0.32, 95% CI 0.11–0.96; nominal P = 0.043; FDR-adjusted P = 0.172), non-intravesical PFS (HR 0.32, 95% CI 0.09–1.18; P = 0.086), and IVRFS (HR 0.21, 95% CI 0.04–1.09; P = 0.063). HER2 IHC 2+/3+ tumors showed exploratory favorable DFS/PFS signals. Grade ≥3 treatment-related adverse events were similar between groups.ConclusionsAdjuvant ADC+ICI showed comparable short-term OS and directionally favorable DFS/PFS trends versus GC, with a distinct toxicity profile. These findings are hypothesis-generating and require prospective validation.

INTRODUCTION:A randomized controlled trial was conducted to compare the clinical efficacy of lateral transperitoneal adrenalectomy (LTA) versus posterior retroperitoneoscopic adrenalectomy (PRA) and to explore suitable surgical approaches for different patients. METHODS:This prospective study enrolled 184 adrenal tumor patients treated at our hospital from May 2023 to October 2025. Patients were randomly assigned to the LTA group or PRA group using minimization. Subgroup analyses were performed based on tumor diameter, location, and pathological type to investigate suitable surgical approaches for tumors with different characteristics. The impact of surgeon qualifications on outcomes was examined to indirectly assess the differences in learning curves. Primary outcomes included operative time, laparoscopic operation time, and blood loss. Secondary outcomes included trocar establishment time, number of trocars, transfusion rates, intraoperative complication rates, conversion rates, analgesic requirement grade on postoperative day 1, postoperative antibiotic use, postoperative recovery time of gastrointestinal function, postoperative drainage time, short-term postoperative complication rates, postoperative length of stay, and total hospitalization cost. RESULTS:The LTA and the PRA groups each comprised 92 patients. No significant differences were observed between LTA and PRA for primary outcomes. PRA demonstrated superiority over LTA in the number of trocars (p = 0.006), intraoperative complication rates (p = 0.047), analgesic requirement grade on postoperative day 1 (p = 0.042), postoperative recovery time of gastrointestinal function (p < 0.001), and postoperative drainage time (p < 0.001). When tumor diameter >3 cm, LTA demonstrated superiority in blood loss (p = 0.007) and intraoperative complication rates (p = 0.032). Subgroup analysis showed that LTA had a significantly higher complication rate than PRA (p = 0.027) when treating right adrenal tumors. Surgeon qualifications significantly influenced operative time (p < 0.001), laparoscopic operation time (p = 0.006), and blood loss (p = 0.002) of PRA, but had no apparent effect on perioperative indicators of LTA. CONCLUSION:Both LTA and PRA are safe surgical methods for treating adrenal tumors, but PRA has advantages, especially for right adrenal tumors, where it can significantly reduce the incidence of complications, but it requires a greater technical challenge for the surgeon. For adrenal tumors with a diameter greater than 3 cm, LTA can be considered. Clinicians should comprehensively consider their technical proficiency, patient characteristics, and tumor features when choosing the appropriate surgical method.

Robot-assisted nephrectomy with renal vein or inferior vena cava (IVC) tumor thrombectomy is a technically demanding procedure used in selected patients with renal cell carcinoma (RCC) and venous tumor thrombus. The research map of this field has not been clearly described, and recent technical, comparative, and systemic-therapy developments make an updated focused analysis timely. We searched the Science Citation Index Expanded of the Web of Science Core Collection from database inception to 4 May 2026. English articles and reviews about robot-assisted nephrectomy or radical nephrectomy with renal vein or IVC tumor thrombectomy for RCC were included. Titles, abstracts, keywords, authors, affiliations, journals, citations, and cited references were extracted. Python 3.11 was used for descriptive analysis, keyword analysis, co-citation analysis, visualization, and clinical theme coding. We included 51 SCIE publications from 2011 to 2026, including 40 articles and 11 reviews. The papers received 1229 citations, with a mean of 24.10 citations per paper and a median of 12. Annual publications peaked in 2020 with 7 papers. The United States published 24 papers, China published 21, and Italy published 8 when all author affiliations were counted. The Chinese People's Liberation Army General Hospital published 14 papers, and the University of Southern California published 7. Ma X, Zhang X, and Wang BJ were the most productive authors. European Urology, Journal of Urology, and Journal of Endourology were the leading journals. After term cleaning, the most frequent keywords were renal cell carcinoma, tumor thrombus, robotic surgery, experience, inferior vena cava, and thrombectomy. This field has moved from early technical exploration to early evidence building. Future work should use multicenter prospective designs and should study high-level IVC thrombus, long-term oncologic outcomes, perioperative safety after neoadjuvant therapy, robotic training, and multidisciplinary care pathways.

Bladder-preserving multimodal therapy has gained increasing recognition for the management of muscle-invasive bladder cancer (MIBC). This study aims to compare the efficacy and safety of disitamab vedotin combined with anti-PD-1 agents (RC48 + PD-1) versus gemcitabine plus cisplatin chemotherapy combined with anti-PD-1 agents (GC + PD-1) among MIBC patients receiving bladder-preserving multimodal therapy. This was a single-center real-world retrospective cohort study. Patients diagnosed with MIBC who received bladder-preserving multimodal therapy at our hospital between January 2021 and September 2024 were enrolled. Participants were stratified into two groups according to their systemic treatment regimens: RC48 + PD-1 group and GC + PD-1 group. Propensity score matching (PSM) was performed to adjust baseline clinical characteristics and mitigate potential selection bias. Primary comparative endpoints between the two cohorts included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). A total of 143 patients with MIBC were initially enrolled, including 68 patients receiving RC48 + PD-1 inhibitor and 75 patients treated with GC + PD-1 inhibitor. After 1:1 PSM to balance baseline characteristics, a matched cohort consisting of 104 patients (52 patients per group) was generated for final analyses. Analysis of the matched cohort revealed that the ORR was significantly higher in the RC48 + PD-1 group than in the GC + PD-1 group (p = 0.013), whereas no statistically significant intergroup difference was observed in DCR. The median follow-up duration was 20 months (range, 8–56 months). Disease progression occurred in 43 patients (41.3

Background:En bloc resection of bladder tumors (ERBT) is a surgical treatment for non-muscle-invasive bladder cancer (NMIBC). However, data on the efficacy and safety of ERBT for tumors ≥3 cm are limited. This study aimed to investigate the technical characteristics and clinical application of β-electrode ERBT in the treatment of bladder tumors ≥3 cm and analyze its feasibility and short-term safety. Methods:Retrospective data were collected from patients with bladder cancer (BC) who underwent β-electrode ERBT between 2021 and 2024. Surgical Procedure: A mark was made 0.5 cm from the tumor margin. The knife tip was inserted into the submucosal layer at the marked site and retracted away from the bladder wall. The tumor was completely resected using a combination of hook dissection and blunt separation, followed by removal. For larger tumors, en bloc resection was also performed, after resecting most of the tumor base, a small portion was left attached to the bladder wall (to suspend the tumor on the bladder wall and prevent it from becoming free-floating). Subsequently, the tumor crown was crushed and aspirated using a tissue morcellator, while the preserved tumor base was removed en bloc for pathological examination. The primary endpoints recorded were recurrence-free survival (RFS) and progression-free survival (PFS), with secondary endpoints including detrusor muscle (DM) presence rate (presence of muscularis propria in specimens) and safety (intraoperative and postoperative complications). Results:This study enrolled 102 patients with tumor size ≥3 cm. The median operative time was 50.0 (IQR: 34.5, 90.0) minutes, with 73 (71.6%) cases involving DM. No obturator nerve reflex occurred intraoperatively in any patient. Postoperative complications were observed in 10 patients, among which urinary tract infection was the most common (n=5). During a median follow-up of 22.5 (IQR: 14.0, 29.3) months, 10 recurrences and 4 progressions were recorded. The 2-year RFS and 2-year PFS were 90.2% and 96.9%, respectively. Conclusions:β-electrode ERBT is a selective surgical approach for bladder tumors ≥3 cm, demonstrating favorable short-term efficacy with minimal intraoperative and postoperative complications, and a good short-term oncological prognosis after surgery.

Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) is frequent, but postoperative recurrence risk is heterogeneous. We developed and multicohort-validated an interpretable postoperative model for IVR risk stratification after RNU. We included 813 patients with pathologically confirmed UTUC treated with RNU across four predefined cohorts: retrospective development (n = 400), retrospective external validation (n = 173), internal prospective validation (n = 166), and external prospective validation (n = 74). Missing data were handled using cohort-specific multiple imputation. A Cox model integrating clinicopathological factors and neutrophil-to-lymphocyte ratio (NLR) was developed and locked in the development cohort, then transported unchanged to validation cohorts. Bootstrap confidence intervals, competing-risk analyses, benchmark comparisons, and sensitivity analyses were performed. The locked Cox + NLR model retained tumor location, ureteroscopic manipulation, hydronephrosis, pathological stage, surgical margin status, lymphovascular/perineural invasion, history of bladder cancer, and NLR. Harrell’s C-indices were 0.709, 0.746, 0.868, and 0.811 across the four cohorts. At the primary 12-month horizon, AUCs were 0.739, 0.771, 0.953, and 0.791, respectively. Low-risk and high-risk groups remained separated under the competing-risk framework. More complex survival machine-learning models did not show a consistent transportability advantage. The 24-month estimates and surveillance simulation were considered exploratory because prospective follow-up was limited. This interpretable postoperative Cox + NLR model showed favorable multicohort performance for IVR risk stratification after RNU. It may support postoperative risk assessment, but prospective implementation studies are needed before surveillance schedules are changed.

Background: The study aims to investigate the clinicopathological differences between early-onset and elderly patients with upper tract urothelial carcinoma (UTUC) and to develop a nomogram for assessing the prognosis of early-onset upper tract urothelial carcinoma. Methods: Patients diagnosed with UTUC between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The clinicopathological characteristics of early-onset and elderly patients were compared,and survival analysis was performed for both groups. Cox regression was used to identify predictors of overall survival (OS) and cancer-specific survival (CSS) in early-onset UTUC patients. Nomograms for OS and CSS were constructed and internally validated using the concordance index, decision curve analysis, receiver operating characteristic curves, and calibration plots. External validation was performed using data from 255 early-onset UTUC patients. Finally, Kaplan-Meier curves were plotted to compare survival outcomes among different risk subgroups. Results： This study included a total of 2694 early-onset patients and 4144 elderly patients. early-onset patients were divided into training (1886 patients) and validation (808 patients) cohorts in a 7:3 ratio. Cox regression analysis identified age, tumor size, T stage, N stage , M stage histologic subtype and chemoradiotherapy as independent risk factors for OS, while age, tumor grade, tumor size, T stage, N stage, and M stage ,histologic subtype and radiotherapy were independent risk factors for CSS. Nomograms of OS and CSS were constructed based on these factors. Both internal and external validations demonstrated good predictive accuracy for the nomograms. For OS, the area under the receiver operating characteristic curve (AUC) values at 1, 3, 5, and 8 years were 0.807, 0.774, 0.760, and 0.736 in the training cohort; 0.811, 0.793, 0.763, and 0.752 in the internal validation cohort; and 0.793, 0.767, 0.754, and 0.730 in the external validation cohort, respectively.Regarding CSS, the area under the receiver operating characteristic curve (AUC) values at 1, 3, 5, and 8 years were observed to be 0.834, 0.822, 0.816, and 0.792 in the training cohort; 0.863, 0.833, 0.811, and 0.820 in the internal validation cohort; and 0.819, 0.815, 0.806, and 0.780 in external validation cohort , respectively.Kaplan-Meier curves showed statistically significant differences in survival outcomes among different risk subgroups for both OS and CSS. Conclusions： This study developed a nomogram based on the SEER database to predict overall survival in patients with early-onset UTUC, aiming to aid in prognostic assessment and guide clinical treatment.

CCT5, a subunit of the chaperonin-containing TCP1 complex, has been implicated in the development of various malignancies. However, its role in bladder cancer remains undefined. This study investigated the functional contribution of CCT5 and its association with Hippo/YAP signaling. Using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), CCT5 expression and its prognostic significance were analyzed. Single-cell and spatial transcriptomics were employed to explore expression patterns and cellular heterogeneity. Functional assessments were conducted in vitro and in vivo using xenografts. To elucidate the underlying mechanisms, RNA-seq was integrated with Western blotting analysis. CCT5 was found to be upregulated in bladder cancer and correlated with poor prognosis and aggressive pathological features. Single-cell and spatial analyses revealed that CCT5 was enriched in malignant epithelial subpopulations with high CNV scores, activated oncogenic pathways, and extensive cell-cell interactions. Functionally, CCT5 promoted proliferation, migration, invasion, and G1/S transition while inhibiting apoptosis; its depletion reduced xenograft growth. At the signaling level, CCT5 knockdown enhanced phosphorylation of MST1, LATS1, and YAP, without significant changes in total protein levels, suggesting activation of Hippo/YAP signaling. These findings highlight CCT5 as an oncogenic factor in bladder cancer, potentially acting through the regulation of Hippo/YAP signaling, and propose its potential as a biomarker and therapeutic target in bladder cancer.

Xenotransplantation has garnered significant attention in recent years, characterized by substantial progress and rapid developments within the field. The objective of this study was to investigate the evolving trends and emerging research hotspots in xenotransplantation through a comprehensive bibliometric analysis. We conducted an analysis of literature published between 1980 and 2025, sourced from the Web of Science Core Collection. Data processing, analysis, and visualization were performed using VOSviewer, CiteSpace, the Bibliometric R package, and Scimage Graphica. A total of 7880 articles spanning 45 years were included in the analysis. The United States emerged as the predominant contributor to the field, both in terms of article output and institutional involvement. Professor David K. C. Cooper was identified as the leading author, with the highest number of publications on xenotransplantation. The journal Xenotransplantation was found to be the most prolific in terms of article publication. Key research hotspots identified through this analysis include the selection of gene-editing strategies for pigs, the use of genetically modified pigs as donors for various cells, tissues, and organs, as well as the focus on clinical trials and translational studies aimed at advancing xenotransplantation.

Triggering receptor expressed on myeloid cells-2 (TREM2) is a key myeloid immune checkpoint for macrophage plasticity. However, its functional landscape in urology is still incomplete. This review addresses this gap by providing the first systematic synthesis of TREM2 in urological malignancies (bladder, prostate, and renal cell carcinomas) and benign conditions. We find a strong correlation between TREM2 upregulation and adverse clinical outcomes in these cancers. Importantly, we highlight the phenomenon of "mechanistic convergence": unlike the high context-dependency of other organ systems, TREM2 appears to drive progression in urological malignancies by a common convergent signaling hub, the PI3K/AKT pathway. This contrasts sharply with its metabolic role in benign prostatic hyperplasia and its protective role in non-malignant renal injury. We also consider the translational potential of TREM2 as a prognostic biomarker (specifically urine detection) and as a therapeutic target to reverse immunotherapy resistance.