[This corrects the article DOI: 10.3389/fphar.2026.1786648.].

Background:Enzalutamide resistance (Enz-R) remains a major clinical challenge in advanced prostate cancer (PCa). Here, we identified resistance-associated long non-coding RNA (lncRNA) PCAT1 and investigated its functional relevance in Enz-R PCa. Methods:Public transcriptomic datasets, bioinformatic analyses, RNA immunoprecipitation (RIP), ChIP-qPCR, and in vitro and in vivo functional assays were used to evaluate the expression, function, and potential mechanism of PCAT1 in Enz-R PCa models. Results:PCAT1 was upregulated in Enz-R PCa models and was associated with adverse clinical features. PCAT1 knockdown inhibited the growth of C4-2 Enz-R cells and 22Rv1 cells and suppressed tumor growth in vivo. Mechanistically, PCAT1 was associated with AR/AR-V7 and supported selected AR-V7-associated downstream outputs without markedly altering AR-V7 protein expression. AR-V7 ChIP-qPCR further suggested that PCAT1 knockdown reduced AR-V7 enrichment at selected regulatory regions, including the KLK3 and PMEPA1 enhancers. In addition, high-dose androgen treatment reduced PCAT1 and AR-V7 expression in our experimental model. Conclusion:PCAT1 contributes to Enz-R PCa growth and may support selected AR-V7-associated transcriptional outputs. PCAT1 may represent a potential therapeutic vulnerability, and the relationship between high-dose androgen treatment, PCAT1 suppression, and AR-V7 signaling warrants further investigation.

Abstract Conventional nanoparticles for tumor imaging and therapy often fail due to poor clearance, prolonged circulation, and toxic off-target effects. We introduce a biomimetic phytic acid (PA)–metal–albumin nanoternary complex that repurposes the body’s natural PA–metal–protein assembly/clearance axis to enable tumor-targeted theranostics. The platform is serum-stable, bioclearable, and supports a broad spectrum of imaging and therapeutic payloads. For example, PA chelates manganese (Mn2+) for high-contrast T1-weighted magnetic resonance imaging, platinum (Pt) for chemotherapy, and radium-223 (Ra-223) for alpha radiotherapy. In the acidic environment of tumor endosomes, the complexes undergo programmed aggregation to maximize intratumoral retention, while systemic elimination follows physiological detox pathways. Released Mn2+ enhances cGAS–STING immune activation, amplifying antitumor responses. This clearance-competent, biomimetic nanoplatform unifies imaging, therapy, and immune modulation, advancing precision oncology with strong translational potential.

Trained immunity offers a promising yet clinically challenging strategy for cancer immunotherapy, as current inducers such as BCG pose safety concerns and their active components remain ill-defined. BCG-derived heat shock protein 70 (BCG HSP70, Dnak) has previously been recognized only as an immune adjuvant, while its role in trained immunity remains unexplored. This study identifies Dnak as a safe, defined inducer that establishes durable central trained immunity through epigenetic and metabolic reprogramming of bone marrow hematopoietic stem cells, conferring protection against bacterial infection. In prostate cancer models, a single Dnak pre-treatment significantly inhibits tumor growth-an effect transferable via bone marrow transplantation and dependent on tumor-associated macrophages. Mechanistically, Dnak-trained macrophages exhibit enhanced glycolysis, mTOR/HIF-1α pathway activation, and M1-like polarization. Notably, O-GlcNAcylation emerges as a previously unrecognized regulator of trained immunity. Furthermore, combining Dnak-induced trained immunity with a tumor vaccine achieves superior tumor control, reshapes the tumor microenvironment, and generates durable memory T cell responses upon rechallenge. These findings establish BCG HSP70 as a safe and effective protein-based trained immunity inducer with translational potential for cancer immunotherapy.

Often linked with the risk of various diseases, blood low-density lipoprotein cholesterol (LDL-C) levels are typically deemed more favorable when lower. The objective of this investigation is to elucidate the link between blood LDL-C levels and the risk of prostate cancer (PCa) in middle-aged and older men without hypertension in the United States. Utilizing continuous data from the National Health and Nutrition Examination Survey (NHANES) database spanning 2003-2010, a selection of 1,223 non-hypertensive men aged ≥ 40 years was made from a pool of 41,156 participants, ensuring no missing information. Regression analyses were employed to investigate the correlation between blood LDL-C levels and the PCa risk, while identifying potential inflection points indicative of threshold effects. Additionally, we scrutinized the linkage between cholesterol-lowering prescription drug usage and PCa. In our study of 2,224 participants, we found no significant correlation between blood LDL-C levels and the PCa risk after adjusting for confounding variables (Odds Ratio = 0.99; P-value > 0.05). However, upon conducting a subgroup analysis, we discovered a meaningful correlation between lower blood LDL-C levels and an increased PCa risk in the non-hypertensive population (Odds Ratio = 0.99; P-value < 0.05). Meanwhile, we identified a threshold effect and a tipping point at an LDL-C levels of 67 mg/dl. Furthermore, a significant correlation was identified between cholesterol-lowering prescription drug usage and a heightened PCa risk in the non-hypertensive population (Odds Ratio = 18.87; P-value < 0.05; P for interaction < 0.05). Our results indicate that in non-hypertensive middle-aged and older men residing in the United States, lower blood LDL-C levels are not necessarily better and the PCa risk escalates when blood LDL-C levels drop below 67 mg/dl, which may guide early screening and prognosis of PCa in specific populations. This finding calls for further validation via larger sample sizes and a more in-depth analysis of PCa history.

Human carcinomas often gain aggressive characteristics and escape cell-type specific treatment regimens through cryptic shifts in lineage states. However, the underlying mechanisms that govern lineage plasticity in carcinomas are undefined. Here in this study, we found that PAX5, a neural/lymphatic transcription factor, contributed to neuroendocrine (NE) lineage transition. PAX5 was highly expressed in aggressive human NE carcinoma cells and tissues but not in non-NE cancer cells and tissues. Deletion of Pax5 in Rb1fl/fl;Trp53fl/fl mice caused a reduction of tumor vessels, loss of NE morphologic features and decreased expression of ASCL1, NCAM, and SYP, whereas ectopic expression of PAX5 in CC10-rtTA;TetO-hEGFRex19del/T790M mice adenocarcinomas and in LNCAP prostate cancer xenografts induces an angiogenic microenvironment and NE morphology. Importantly, antiangiogenic drugs reduced NE features of Rb1fl/fl;Trp53fl/fl tumors and blocked PAX5-induced NE transformation. These studies demonstrate an essential role of angiogenic microenvironment in transition/maintenance of NE lineage, suggesting that targeting PAX5 and its downstream signaling may modulate lineage transitions responsible for treatment failure in both SCNCs and adenocarcinomas.

Benign prostatic hyperplasia (BPH) is a common age-related condition characterized by prostate enlargement, which is influenced by hormonal imbalances and altered signaling pathways. In this study, we investigated the effects of different doses of treatment on prostate tissue in a rat model of BPH, focusing on the G protein‑coupled estrogen receptor (GPER), the downstream signaling molecule Yes-associated protein (YAP), and its phosphorylated form (p-YAP). We measured hormone levels, protein expression, and histopathological changes to evaluate the impact of treatment on prostate growth. Serum estrogen and testosterone levels were assessed using enzyme‑linked immunosorbent assay (ELISA), while GPER, YAP, and p-YAP protein expression were analyzed by Western blot (WB). Immunofluorescence assays for Ki-67 and Caspase-3 were also performed. Our results showed that 17β-estradiol (E2) 50 μg/kg and E2 100 μg/kg treatment significantly increased GPER and p-YAP protein expression, with corresponding increases in prostate tissue proliferation and reduced apoptosis, as indicated by Ki-67 and Caspase-3 expression. In contrast, the inhibitor treatment significantly decreased GPER and p-YAP expression, promoting apoptosis and reducing prostate enlargement. Hormonal assays revealed that estrogen levels were elevated and testosterone levels were reduced in the E2 50 μg/kg and E2 100 μg/kg groups, whereas inhibitor treatment partially reversed these changes in circulating and intraprostatic sex hormone levels. These findings suggest that the GPER/YAP signaling pathway plays a key role in BPH progression and that targeting this pathway may offer a novel therapeutic approach for managing BPH.

Prostate cancer (PCa) is a prevalent malignancy of the male reproductive system and ranks as the second most common cancer in men worldwide. The prognosis and clinical management of PCa are closely linked to its pathological grade; however, the high heterogeneity of the disease poses significant challenges in these assessments. Prostate cancer associated 3 (PCA3), an upregulated long non-coding RNA (lncRNA) in PCa, has been established as a urinary biomarker for PCa detection. Nevertheless, its potential role in distinguishing pathological grades remains unclear. In this study, we investigated the association between PCA3 expression and PCa pathological grades. First, we conducted a pan-cancer bioinformatics analysis of PCA3 expression across 32 cancer types, confirming its high specificity for PCa. Next, we performed least absolute shrinkage and selection operator (LASSO) regression, identifying 18 GS-associated lncRNAs. A Gaussian distribution analysis revealed that PCA3 exhibited the strongest PCa-specific expression among these lncRNAs. Furthermore, logistic regression analysis demonstrated that PCA3 expression was significantly higher in poorly differentiated PCa than in well-differentiated PCa. To validate these findings, we constructed a PCA3 promoter-driven transcriptional reporter system, which exhibited elevated activity in lower-grade PCa, reinforcing the differential expression pattern of PCA3 across pathological grades. Our findings suggest that PCA3 could serve as a robust and clinically valuable biomarker for predicting PCa pathological grade.

PURPOSE:The comparative real-world adverse event (AE) reporting profiles of enzalutamide, olaparib, and lutetium Lu-177 vipivotide tetraxetan remain incompletely characterized in prostate cancer. As sequential and combination strategies continue to evolve, understanding post-marketing AE reporting patterns in broader clinical populations is important. This study aimed to characterize time-dependent AE reporting profiles and descriptively summarize sparse reports involving concomitant use of all three agents using a large pharmacovigilance database. METHODS:We performed a retrospective disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database from each drug's approval date through the third quarter of 2025. Reports were included when the drug of interest was listed as the primary suspect drug and prostate cancer was recorded as the therapeutic indication. Signal detection used four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN). Stratified analyses by age and time-to-onset were conducted, and reports involving concomitant use of all three agents were summarized descriptively. RESULTS:A total of 8,341 enzalutamide, 217 olaparib, and 486 lutetium Lu-177 vipivotide tetraxetan primary-suspect reports with prostate cancer as the indication were included. Distinct AE reporting patterns were observed across the three individual-drug cohorts. Olaparib showed a strong disproportionality signal for anaemia (ROR 8.77), whereas lutetium Lu-177 vipivotide tetraxetan was characterized by signals for dry mouth (ROR 18.08) and thrombocytopenia. Time-to-onset analysis showed that many reported AEs occurred within the first 90 days after treatment initiation. Seven reports involved concomitant use of all three agents; this subset was too sparse to support reliable signal detection or inference regarding drug-drug interaction. CONCLUSION:This study provides a comparative overview of post-marketing AE reporting patterns for three major prostate cancer therapies. The findings were broadly consistent with established toxicity profiles and suggested that early treatment may represent an important period for clinical observation. Because reports involving concomitant use of all three agents were extremely sparse, no reliable conclusions regarding drug-drug interaction, additive toxicity, or synergistic toxicity can be drawn. Prospective studies are needed to characterize the safety of emerging multi-agent treatment strategies. Interpretation of cross-drug comparisons should additionally account for substantial inter-cohort differences in reporter type and reporting country.

e17103 Background: Apalutamide (APA) combined with androgen deprivation therapy (ADT) is the standard care for mHSPC and is associated with significant survival benefits. Given limited data from Chinese patients (pts), this study aimed to conduct the largest observational investigation to date to assess the real-world effectiveness and safety of APA plus ADT in Chinese pts with mHSPC, with a focus on prostate-specific antigen (PSA) decline and disease progression. Methods: This retrospective, multicenter observational study enrolled adult pts with mHSPC who initiated on APA plus ADT between 1 Jan 2022 and 31 May 2024 (index date), with follow-up through 31 May 2025, utilizing data from chart review. The observation period for each pt spanned from the index date to loss to follow-up, death, or 1-year follow-up. The primary endpoint was the proportion of pts achieving PSA≤0.2 ng/mL (PSA0.2) at Month (M) 3. Other endpoints included proportion of pts achieving a decrease in PSA ≥50% or ≥90% (PSA50/90), PSA progression, clinical and radiographic disease progression events within 12 mo. The number and proportion of pts achieving PSA0.2 or PSA50/90 along with their 95% confidence intervals (CIs) were determined by using Clopper–Pears on exact method on the basis of observed case data. Subgroup analyses were performed by age ( < 65, ≥65 to < 75, and ≥75 yr) and Gleason score (≤7 or > 7) on PSA0.2. Adverse drug reactions (ADRs) were collected for safety evaluation. Results: There were 300 pts with mHSPC treated with APA plus ADT analyzed. Median treatment duration was 12.8 (range 0.1–13.5) mo. Baseline characteristics were as follows: median age 72 (range 40–97) yr, Gleason score > 7 in 84% (172/204) of pts, tumor stage T3 in 22/84 and T4 in 51/84 pts, median PSA100 (range 0.1–5000) ng/mL. PSA0.2 response was 41.1% at M3, increasing to 62% at M6 and 69.7% at M12. PSA50 and PSA90 responses were 98.8% and 92% at M3, respectively. PSA progression (increase ≥50% and ≥5 ng/mL above nadir) occurred in 7 pts; clinical and radiographic disease progression occurred in 2 pts and 1 pt. Regarding safety analysis, ADRs were reported in 13% of pts, with ADRs (grade 3–4) reported in 1%. 4 deaths were reported. PSA0.2 response did not show meaningful difference across subgroups. Conclusions: The CAPABLE, the largest published APA real-world study in China, reveals a notably high PSA response for APA plus ADT, with infrequent progression reported, indicating a favorable prognosis for pts with mHSPC. The regimen also has a tolerable safety profile. PSA response among pts with mHSPC after APA plus ADT treatment. % (n/N) 95% CI PSA0.2M3M6M12 41.1% (76/185)62% (98/158)69.7% (99/142) 33.9%–48.5%54%–69.6%61.5%–77.1% PSA50M3M6M12 98.8% (160/162)97.1% (134/138)95.3% (121/127) 95.6%–99.9%92.7%–99.2%90%–98.2% PSA90M3M6M12 92% (149/162)91.3% (126/138)92.9% (118/127) 86.7%–95.7%85.3%–95.4%87%–96.7%

BackgroundDoxorubicin (DOX) resistance remains a major obstacle to effective chemotherapy in breast cancer. However, the pharmacologically actionable regulators sustaining this resistant phenotype and its therapeutic vulnerabilities remain incompletely defined.MethodsDOX-resistant breast cancer cell models were established and treated with the EZH2 inhibitors tazemetostat or GSK126, alone or in combination with DOX. Cell viability, oxidative stress, DNA damage, and mitochondrial function were assessed in vitro. Transcriptomic profiling was performed to identify pathway alterations. A pH-responsive liposomal system for delivery of DOX and tazemetostat was developed and evaluated in vivo.ResultsEZH2 was highly expressed in breast cancer and correlated with poor clinical outcomes. DOX treatment induced adaptive upregulation of EZH2 in both sensitive and resistant cells. Pharmacological inhibition of EZH2 markedly restored DOX sensitivity and exhibited strong synergistic cytotoxicity in resistant models. EZH2 blockade enhanced DOX-induced oxidative stress and DNA damage, with concomitant suppression of multiple DNA repair pathways and increased γH2AX accumulation. Transcriptomic and functional analyses revealed disrupted mitochondrial function and energy metabolism, characterized by loss of mitochondrial membrane potential and ATP depletion. In vivo, combined EZH2 inhibition and DOX significantly suppressed tumor growth, while pH-responsive liposomal delivery further enhanced antitumor efficacy and reduced systemic toxicity.ConclusionEZH2 is a critical determinant of DOX resistance in breast cancer by sustaining DNA damage tolerance and metabolic homeostasis. Pharmacological targeting of EZH2 in combination with DOX represents a rational strategy to overcome chemoresistance in breast cancer.

Cytoreductive radical prostatectomy (CRP) may improved outcomes in men with low-volume metastatic hormone-sensitive prostate cancer (mHSPC), but its roles in high-volume disease remains controversial. Contemporary systemic therapy has enabled an increasing proportion of patients with high metastatic burden to achieve deep disease remission, creating a potential window to assess additional benefit from primary tumor resection. We aimed to investigate the feasibility and oncological outcomes of CRP in patients with mHSPC, including those with high-volume disease. This multicentre, prospective study recruited patients with histologically diagnosed mHSPC from September, 2018 to October, 2023. All eligible patients received lifelong androgen deprivation therapy combined with novel androgen receptor pathway inhibitors and achieved a deep biochemical response (prostate-specific antigen [PSA] < 0.2 ng/ml). Patients either underwent CRP plus standard of care (SOC) or received SOC only. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints were overall survival (OS) and PSA progression-free survival (PSA-PFS). Multivariable Cox proportional hazards models, incorporating CRP as a time-dependent covariate, were used to evaluate associations with outcomes. Propensity score matching (PSM) was applied to balance baseline characteristics between groups. Of 126 patients enrolled, 62 underwent CRP + SOC and 64 received SOC. At a median follow-up of 46.7 months, patients in the CRP + SOC group demonstrated prolonged survival compared with those receiving SOC alone. Among 74 patients with high-volume diseases, CRP remained associated with significant longer rPFS (hazard ratio [HR] 0.36, p = 0.035), OS (HR 0.10, p = 0.006), and PSA-PFS (HR 0.32, p = 0.017). Multivariate Cox regression analysis identified CRP as an independent prognostic factor (all p < 0.05). After PSM, 30 well-balanced pairs were identified. In the matched cohort, CRP + SOC was consistently showed improved rPFS (HR 0.31, p = 0.036), OS (HR 0.22, p = 0.031), and PSA-PFS (HR 0.25, p = 0.009) compared with SOC alone. CRP is feasible and associated with improved oncological outcomes in well-selected patients with mHSPC who achieved deep biochemical response to contemporary systemic therapy, including those with high-volume metastatic disease. However, these findings require validation in larger, prospective, randomized controlled trials.

To ascertain role of the fanconi anemia complementation group G (FANCG) gene in prostate cancer (PCa) and the suitability of the FANCG gene as a prognostic biomarker for PCa. We assessed the expression of FANCG using an analysis of publicly available data sets and cell lines. Physiological functioning of the cells was evaluated through MTT assays and migration assays. Co-expressed genes and enrichment analysis were conducted to probe the biological significance of FANCG in PCa. Quantitative real-time polymerase chain reaction (qPCR) was utilized to detect the expression levels of hub genes (MCM7, MCM5, POLD1, POLA2, LIG1) associated with FANCG. We observed a significant upregulation of FANCG expression in PCa patients and cell lines. Furthermore, immunohistochemical analysis demonstrated markedly higher FANCG protein expression in PCa tissues compared to non-cancerous PCa tissues. Downregulation of FANCG significantly inhibited cell proliferation and migration potential. Evaluation of FANCG-related hub genes (MCM7, MCM5, POLD1, POLA2, and LIG1) revealed their close association with cell cycle-related signaling pathways. Upregulation of FANCG mRNA expression in PCa tissues significantly correlated with high serum PSA levels, advanced pathological stage, high Gleason score, shorter overall survival time, and shorter disease-free survival time. This study suggests that FANCG likely plays a pivotal role in PCa progression. In addition, increased FANCG expression may serve as an indicator of poor disease-free survival and an adverse prognosis for PCa patients.

Objectives:To propose a comprehensive scoring system for adrenal tumors ≤ 6cm and evaluate its rationality and validity. Materials and methods:This study retrospectively analyzed 268 patients with primary adrenal tumors who underwent laparoscopic surgery from January 2018 to December 2022 and all of them met the inclusion criteria. Evaluation scores were calculated for gender (G), body mass index (BMI) (B), tumor diameter (D), the relative position of the tumor to the kidney (K), the relative position of the tumor and the blood vessels (V) and the tumor location in the adrenal gland (A). Then, the total scores were correlated with the operation results, so as to verify the feasibility of GBDKVA in evaluating the surgical risk. Results:The GBDKVA score showed a consistent and statistically significant correlation with operation time (OT) and blood loss (BL), as well as a correlation with postoperative complications in patients (p < 0.01), but no significant correlation was found with recovery time of gastrointestinal function, bed rest days, indwelling drainage tube days and postoperative hospitalization time were opposite. Conclusions:GBDKVA score is reliable for preoperative risk assessment of patients with adrenal tumors ≤6cm.

Robot-assisted radical prostatectomy (RARP) has emerged as a primary treatment modality for localized prostate cancer. In this context, we report a novel surgical technique termed Retzius-sparing robot-assisted laparoscopic radical prostatectomy with retrograde release of the neurovascular bundle (RNRS-RARP). This study aims to assess the perioperative, oncological, and functional outcomes of RNRS-RARP across varying prostate volumes. A retrospective analysis was conducted on clinical data retrieved from 298 patients who underwent RNRS-RARP from October 2021 to September 2023. Patients were stratified into three groups based on pathological prostate weight: ≤ 30 g, 30–50 g, and ≥ 50 g. Comparative analyses were performed on perioperative and postoperative oncological and functional outcomes among the three groups to discern variations. Separate analyses were performed for patients who received neoadjuvant therapy and those who did not. Additionally, independent predictors of immediate continence following RNRS-RARP were investigated. Patients with larger prostate volumes were significantly older and have higher body mass index and prostate-specific antigen (PSA) (all p < 0.05). Larger prostate volumes exhibited prolonged median console time (65 vs. 70 vs. 90 min, p < 0.01) and increased median estimated blood loss (95 vs. 90 vs. 100 ml). There were no significant differences in duration of catheterization, length of stay, postoperative complications, positive surgical margin, PSA recurrence after 6 months, 1 month and 3 months continence. Immediate continence worsened with increasing prostate volume (80.0

Heat shock proteins (HSPs), particularly the 70 kDa heat shock protein (Hsp70), are crucial for cellular functions such as protein folding, refolding, and regulation of protein activity. Mycobacterium tuberculosis Hsp70 (DnaK) has attracted attention for its potential as a vaccine adjuvant due to its immunostimulatory properties. This review covers the following topics: an overview of cancer vaccines, introduction to Hsp70, research on DnaK in dendritic cells (DCs), DnaK's role in the tumor immune microenvironment, its safety profile, and insights for vaccine design. DnaK consists of an N-terminal nucleotide-binding domain and a C-terminal peptide substrate-binding domain, connected by a flexible linker. It has been shown to enhance DC maturation, facilitate antigen presentation, and activate T cells. DnaK stimulates Toll-like receptor 4 (TLR4) and CD40 on antigen-presenting cells, promoting both maturation and the secretion of pro-inflammatory cytokines. Additionally, DnaK can enhance antigen presentation through CD91 and DC-SIGN receptors on DCs. However, the immunosuppressive environment within tumors poses challenges to DC activation. DnaK may influence this tumor microenvironment by interacting with macrophages, scavenger receptors, and natural killer (NK) cells, potentially overcoming some of these barriers. Compared to traditional adjuvants like lipopolysaccharide (LPS), DnaK has a favorable safety profile. Its conserved structure and low toxicity make it a promising candidate for vaccine development. Insights from studies on DnaK suggest strategies to improve vaccine efficacy, such as combining it with TLR agonists and leveraging its interaction with DC-SIGN to promote targeted activation of DCs. In conclusion, DnaK shows significant potential as an adjuvant in vaccine design. Understanding its structural and functional roles, as well as its effects on the immune microenvironment, provides valuable insights for the development of more effective and targeted vaccines against infectious diseases and cancer. Further research is needed to elucidate its specific mechanisms of action and optimize its use in vaccine formulations.

This study aimed to develop and validate a nomogram for predicting recurrence-free survival (RFS) in clinical T1 (cT1) clear cell renal cell carcinoma (ccRCC) following nephrectomy. Additionally, it explored transcriptional profiles across distinct risk groups. Data from 2,492 cT1 ccRCC patients who underwent nephrectomy at The Second Hospital of Tianjin Medical University were analyzed. Univariate and multivariate Cox proportional hazards regression analyses were conducted to identify independent predictors of RFS. A nomogram was constructed and validated using a training cohort (n = 1744) and an internal validation cohort (n = 748). Model performance was evaluated using the concordance index (C-index), calibration plots, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and Kaplan–Meier survival curves. An external validation was performed using The Cancer Genome Atlas (TCGA) ccRCC dataset. Furthermore, Cox-Lasso regression analysis was applied to identify risk-associated genes in the high-risk group. Age, surgical margin status, Fuhrman grade, and pT3a upstage were identified as independent predictors. The areas under the ROC curve (AUC) for 3-year and 5-year RFS were 0.748 and 0.762 in the training cohort; 0.777 and 0.776 in the internal validation cohort; and 0.706 and 0.746 in the external validation cohort. Kaplan-Meier analysis showed significant differences in RFS between low- and high-risk groups across all cohorts (p < 0.0001, p < 0.0001, p = 0.0010, respectively). Nine genes, including MMP13, ITPKA, ATG9B, and CACNA1B, were identified as poor prognosis markers. We developed and validated a robust nomogram for predicting RFS in cT1 ccRCC patients after nephrectomy, offering valuable insights for individualized patient management.

BACKGROUND:Bladder cancer (BCa) is one of the most common types of cancers prevalent in the global populace, and it is predominantly detected among men. The role of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in promoting invasion and metastasis in cancers is well known. Despite this, the precise regulatory mechanism by which CEACAM6 contributes to BCa progression remain poorly understood, which is precisely the focus of the present study. METHODS:Our research generated BCa cell lines with CEACAM6 overexpression/knockdown to evaluate the functional significance of CEACAM6. We assessed how the modulation of CEACAM6 influences cell proliferation both in vitro and in vivo on BCa progression. In addition, the effect of CEACAM6 on glycolytic activity was also explored. The co-localization, co-immunoprecipitation, ubiquitination studies, and rescue experiments were performed to understand the molecular interaction between CEACAM6 and alpha-Enolase 1 (ENO1). RESULTS:Our data show that high CEACAM6 expression promotes proliferation, invasion, migration, and clonogenicity of BCa cells. Additionally, CEACAM6 binding to ENO1 and maintain its stability, leading to increased glycolytic activity and invasiveness and proliferative of BCa cells. CONCLUSION:Our study demonstrated that CEACAM6 regulates glycolysis via the ENO1-AKT/mTOR axis. These results offer new evidence about previously unexplored molecular mechanisms driving BCa progression.

This study aimed to compare the outcomes of neoadjuvant novel hormonal therapy (NHT) versus classical hormonal therapy (CHT) before radical prostatectomy (RP) in patients with locally advanced prostate cancer. Propensity score matching (2:1) was performed to minimize the effect of confounders at our center. We retrospectively analyzed 99 patients who received neoadjuvant hormonal therapy for 3–6 months from March 2019 to April 2023. The novel hormonal agents included apalutamide, darolutamide, or enzalutamide, whereas the classical hormonal agent was bicalutamide. The primary endpoint was pathological response. Secondary outcomes included prostate specific antigen (PSA) complete response rate, biochemical recurrence-free survival (bRFS), and biochemical response rate. After propensity score matching, 63 patients were matched to the CHT group and 36 patients were matched to the NHT group. All patients received androgen deprivation therapy. Pathological response Group 0 was not observed in either group; 41.3