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Urinary System Bladder Anatomy Three-Dimensional
Bladder Cancer, Genitourinary Cancer, Argentina, Australia, Belgium, Canada, China, Czech Republic (Czechia), Denmark, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, Poland, Russia, Singapore, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States, NCT04223856, Phase 3, EV-302, ESMO 2024

Impact of Nectin-4 Expression on EV+P in mUC

KEY TAKEAWAYS The EV-302 phase 3 trial aimed to evaluate how Nectin-4 expression affects outcomes with 1L EV+P versus chemotherapy in mUC. Researchers noticed that Nectin-4 expression does not predict the benefit of 1L EV+P treatment in mUC. In the phase 3 EV-302...

Sep 18, 2024

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Low HALP Scores Predict Bladder Cancer Recurrence After UTUC

KEY TAKEAWAYS

  • The study aimed to investigate how the HALP score affects pathologic results and bladder cancer recurrence in patients with UTUC.
  • Results showed that lower HALP scores are linked to advanced disease, higher grade, and increased bladder cancer recurrence risk.

Mehmet Yoldas and the team aimed to investigate how the haemoglobin, albumin, lymphocyte, and platelet (HALP) score impacts pathologic outcomes and bladder cancer recurrence (BCR) in patients who underwent surgery for upper urinary tract tumors (UTUCs).

Researchers calculated HALP scores for all patients. They compared demographic data, preoperative blood parameters, pathologic results, and bladder cancer recurrence status between patients with low and high HALP scores.

Results showed that haemoglobin (11.2±2.3 g/dL vs. 12.9±2.4 g/dL), albumin (4.0±0.8 g/dL vs. 4.4±0.9 g/dL), and HALP score (38.2±2.9 vs. 43.4±3.1) were significantly lower in the BCR (+) group compared with the BCR (-) group (P<0.001). The ROC curve indicated an optimal HALP score cut-off point of 40.8. Multivariate analyses demonstrated that the HALP score was effective for Tumour Grade, Tumour Stage, and BCR.

The study concluded that lower HALP scores are associated with more advanced stages, higher-grade pathologic outcomes, and an increased risk of BCR.

No funding information was available.

Source: https://pubmed.ncbi.nlm.nih.gov/39208822/

Yoldas M, Arikan Y, Kuvvet Yoldas T. (2024). “The Effect of the HALP Score on the Development of Bladder Cancer Recurrence in Patients Undergoing Radical Nephroureterectomy for Upper Urinary Tract Tumours.” Der Einfluss des HALP-Scores auf die Entwicklung eines Blasenkrebsrezidivs bei Patienten, die sich einer radikalen Nephroureterektomie aufgrund eines Tumors des oberen Harntrakts unterziehen. Aktuelle Urol. 2024;55(5):452-457. doi:10.1055/a-2359-7990

Enhanced Fuhrman Grading in ccRCC via Radiomics and Spiral CT

KEY TAKEAWAYS

  • The study aimed to investigate the effectiveness of radiomics-based multilayer spiral CT imaging in accurately predicting Fuhrman pathological grading for ccRCC.
  • Researchers noticed that radiomics-based multilayer spiral CT imaging significantly enhances the accuracy of Fuhrman pathological grading in ccRCC.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and accurate pathological grading is essential for prognosis and treatment planning. However, conventional methods using the Fuhrman pathological grading system have significant limitations, often leading to inconsistent and subjective assessments.

Bolin Liu and the team aimed to investigate the potential of using radiomics-based multilayer spiral computed tomography (CT) imaging as a non-invasive, more reliable alternative for predicting Fuhrman pathological grading in ccRCC.

They performed an inclusive retrospective analysis of the clinical data of patients with ccRCC admitted to the hospital from March 2023 to March 2024. The patients were categorized into low-grade (Fuhrman grades I and II) and high-grade (Fuhrman grades III and IV) groups.

Advanced statistical methods, including correlation analysis, receiver operating characteristic (ROC) curves, and the construction of a joint predictive model, were utilized to evaluate the predictive value of radiomics-based multilayer spiral CT imaging indicators for Fuhrman pathological grading in ccRCC. The primary outcome measure focused on determining how effectively these imaging omics indicators could predict the Fuhrman pathological grading in patients with ccRCC.

About 101 patients with ccRCC clinical data were examined, with 56 cases classified as low-grade and 45 cases as high-grade. Notable distinctions were observed in the grey-level co-occurrence matrix (GLCM) features between low and high Fuhrman grading groups, including contrast (0.24 ± 0.08 vs. 0.33 ± 0.09), energy (0.73 ± 0.05 vs. 0.67 ± 0.06), and homogeneity (0.63 ± 0.05 vs. 0.57 ± 0.05) (P < 0.001).

The CT imaging characteristics also demonstrated substantial variation between the low and high Fuhrman grading groups, with enhancement homogeneity (0.34 ± 0.08 vs. 0.26 ± 0.08) and washout half-time (28.57 ± 4.35 vs. 34.72 ± 5.62) showing significant differences (P < 0.001).

Significant correlations were identified between Fuhrman pathological grading and enhancement homogeneity (r = 0.476), washout half-time (r = -0.519), contrast (r = 0.454), energy (r = -0.453), and homogeneity (r = -0.541). The predictive value of these features was highlighted, with a combined imaging genomics model demonstrating an area under the curve of 0.929.

The study concluded that radiomics-based prediction using multilayer spiral CT imaging offers significant potential for accurately predicting Fuhrman pathological grading in clear cell renal cell carcinoma (ccRCC), thereby enhancing the precision of non-invasive diagnostic methods.

No funding information was given.

Source: https://pubmed.ncbi.nlm.nih.gov/39104236/

Liu B, Liu A, Wu Y, et al. (2024). “Enhancing the Efficacy of Radiomics-Based Prediction of Fuhrman Pathological Grading in Renal Clear Cell Carcinoma Using Multilayer Spiral CT Imaging.” Arch Esp Urol. 2024;77(6):674-680. doi:10.56434/j.arch.esp.urol.20247706.92

ERCC Family in Pan-Cancer and ERCC2 in Bladder Cancer

KEY TAKEAWAYS

  • The study aimed to explore ERCC gene expression’s link to prognosis and validate ERCC2’s role in bladder cancer.
  • The ERCC gene family, particularly ERCC2, shows promise as a potential target for cancer treatment due to its association with tumour development and progression.

Single nucleotide polymorphisms (SNPs) within DNA repair genes can disrupt DNA repair mechanisms, potentially causing genetic instability and increasing the risk of cancer, including bladder cancer. The Excision Repair Cross-Complementation (ERCC) family is crucial for nucleotide excision repair, but its impact on bladder cancer prognosis and the immune microenvironment is not yet fully understood.

Siyang Zhang and the team aimed to characterize the ERCC family’s multi-omics profile and investigate its roles in tumour prognosis and the immune microenvironment.

Researchers conducted a bioinformatics analysis using publicly available data from 33 cancer types to examine the association between ERCC gene expression, patient prognosis, and clinical characteristics. The study also included in vitro assays, specifically CCK-8, colony formation, wound healing, and Transwell assays, to validate the role of ERCC2 in bladder cancer.

Analysis revealed a correlation between ERCC expression variations across multiple cancer types, patient prognosis, and the tumour microenvironment (TME). After adjusting for multiple testing using the Benjamini-Hochberg procedure, ERCC expression levels remained significantly correlated with patient prognosis in several cancer types (P< 0.05).

Furthermore, drug sensitivity studies indicated a strong correlation between ERCC expression and the sensitivity of various anticancer drugs. In vitro cell behaviour assays demonstrated that knocking down ERCC2 gene expression significantly inhibited the proliferation, migration, and invasion of bladder cancer cells.

The in-depth analysis of ERCC differential expression and its association with immune-related indicators, the distinctive TME, and patient prognosis has confirmed the potential role of ERCC2 in bladder cancer development and progression. Consequently, the ERCC gene family is anticipated to be a promising candidate for cancer treatment and warrants further exploration.

This work was supported by the Taizhou Science and Technology Program.

Source: https://pubmed.ncbi.nlm.nih.gov/39192988/

Zhang S, Guan Z, Xia Q, et al. (2024). “Bioinformatics analysis of ERCC family in pan-cancer and ERCC2 in bladder cancer.” Front Immunol. 2024;15:1402548. Published 2024 Aug 13. doi:10.3389/fimmu.2024.1402548

YAP1 Downregulation Impacts YTHDF3 and SMAD7 in BCSCs

YAP1 Downregulation Impacts YTHDF3 and SMAD7 in BCSCs

KEY TAKEAWAYS

  • The study aimed to explore YAP1 knockdown’s effect on BCSCs, focusing on YTHDF3-mediated stabilization of SMAD7.
  • Researchers noticed that silencing YAP1 in BCSCs impedes YTHDF3-mediated degradation of m6A-modified SMAD7, resulting in reduced cell stemness.

The previous study established the oncogenic role of Yes-associated protein 1 (YAP1) in bladder cancer (BLCA). Building on this, the current research focuses on the effects of YAP1 on bladder cancer stem cells (BCSCs) and explores the underlying mechanisms involved.

Dandan Qiu and the team aimed to assess the impact of YAP1 knockdown on BCSCs, particularly examining how it influences YTHDF3-mediated degradation of m6A-modified SMAD7 and its subsequent effect on cell stemness.

They performed an inclusive analysis involving BCSCs derived from human BLCA cells (UMUC3) treated with cisplatin, identified by CD133+ expression via flow cytometry. They utilized bioinformatics to analyze YAP1 interaction proteins and N6-methyladenosine (m6A) modifications on mothers against decapentaplegic homolog 7 (SMAD7).

BCSCs were transfected, and subsequent analyses of SMAD7 m6A levels, YTH domain-containing family proteins 3 (YTHDF3)-SMAD7 interactions, and YAP1/YTHDF3 expression were conducted using methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and quantitative reverse transcription PCR (qRT-PCR). The proliferation of BCSCs was assessed through 5-Bromo-2-deoxyuridine (BrdU) staining.

Migration, invasion, and tumor sphere formation of UMUC3/BCSCs were evaluated using Transwell assays and tumor sphere formation assays. Western blot assays were employed to measure expressions of YAP1, YTHDF3, SMAD7, transforming growth factor (TGF)-β1, and stemness markers in UMUC3/BCSCs.

The BCSCs showed a higher CD133+ ratio, increased expressions of stemness markers, YAP1, YTHDF3, and TGF-β1, along with reduced SMAD7 expression and enhanced invasion, migration, and tumor sphere formation capabilities were observed compared to UMUC3 cells. YAP1 knockdown led to a decrease in SMAD7 m6A levels and disrupted the YTHDF3-SMAD7 interaction in BCSCs.

Silencing YAP1 resulted in reduced cell growth, invasiveness, migration, and tumor sphere formation, alongside lower levels of stemness-associated proteins, YTHDF3, and TGF-β1, while increasing SMAD7 expression in BCSCs. However, these effects were counteracted by YTHDF3 overexpression.

The study concluded that silencing YAP1 in BCSCs impedes the YTHDF3-mediated degradation of m6A-modified SMAD7, leading to a reduction in cell stemness.

No funding information was given for this source.

Source: https://pubmed.ncbi.nlm.nih.gov/39054719/

Qiu D, Gao L, Yu X. (2024). “Knockdown of YAP1 Reduces YTHDF3 to Stabilize SMAD7 and thus Inhibit Bladder Cancer Stem Cell Stemness.” Discov Med. 2024;36(186):1486-1498. doi:10.24976/Discov.Med.202436186.138

Cryptotanshinone Targets NLRP3 to Inhibit BC Progression

KEY TAKEAWAYS

  • The study aimed to investigate cryptotanshinone’s effect on NLRP3 in BC under an inflammatory microenvironment.
  • Researchers noticed that cryptotanshinone suppresses BC progression by inhibiting NLRP3 expression.

Bladder cancer (BC) is one of the most common malignancies of the urogenital system. This study assessed the role of nucleotide-binding oligomerization domain and leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) in BC. They examined the effects of cryptotanshinone on BC malignant behaviors and NLRP3 expression within a lipopolysaccharide (LPS)-induced inflammatory microenvironment.

Chenye Tang and the team aimed to assess the interaction between cryptotanshinone and NLRP3 in the context of BC, specifically within an LPS-induced inflammatory setting.

They performed an inclusive analysis by collecting BC tissue specimens from 62 patients for immunohistochemical detection of NLRP3 protein expression. Both BC and normal urothelial cell lines were cultured to detect NLRP3 mRNA and protein levels. To mimic the inflammatory tumor microenvironment, BC cells were pretreated with LPS.

These cells were then incubated with either a low or high dose of cryptotanshinone to evaluate its impact on tumor cell malignant behaviors. Additionally, BC cells were transfected with NLRP3 cDNA to confirm the specific role of NLRP3 in cancer progression in vitro.

About the results, high NLRP3 expression was found to be associated with larger tumor diameters (>2 cm), muscle invasion, and metastasis. Both NLRP3 mRNA and protein levels were significantly higher in BC cells compared to normal urothelial cells. LPS pretreatment notably increased NLRP3 and inflammatory cytokine expression in BC cells, leading to enhanced cell viability, migration, and invasion.

However, cryptotanshinone effectively reduced the LPS-induced upregulation of NLRP3 and inflammatory cytokines, thereby inhibiting BC cell malignant progression. Furthermore, overexpression of NLRP3 via NLRP3 cDNA transfection further accelerated BC cell malignant progression following LPS stimulation and countered the inhibitory effects of cryptotanshinone on LPS-induced malignant behaviors in BC cells.

The study concluded that NLRP3 may have oncogenic activity in BC, and the antitumor effects of cryptotanshinone observed in vitro appear to be linked to its ability to inhibit NLRP3 expression.

No funding information was given for this source.

Source: https://pubmed.ncbi.nlm.nih.gov/39144184/

Tang C, Guo X, Li Y, et al. (2024). “Cryptotanshinone Inhibits Bladder Cancer Cell Malignant Progression in a Lipopolysaccharide-Induced Inflammatory Microenvironment through NLRP3 Inhibition.” Mediators Inflamm. 2024;2024:8828367. Published 2024 Jan 30. doi:10.1155/2024/8828367

Oncological Outcomes of POPRC vs SRC in Female Bladder Cancer

KEY TAKEAWAYS

  • The study aimed to compare oncological outcomes and quality of life between pelvic organ-preserving and SRC in women with bladder cancer.
  • Researchers noticed that stricter criteria and additional evidence are needed for POPRC to ensure optimal oncological outcomes.

Pelvic organ-preserving radical cystectomy (POPRC) has been reported to result in a better postoperative quality of life in females with bladder cancer compared to standard radical cystectomy (SRC). However, its oncological outcomes remain a concern.

Chuanlin Wang and the team aimed to assess the comparative oncological outcomes and quality of life between POPRC and SRC in female bladder cancer patients, addressing the need for more robust evidence to validate the benefits of POPRC in terms of both survival and patient well-being.

They performed an inclusive analysis using data from the Surveillance, Epidemiology, and End Results (SEER) database to identify female bladder cancer patients who underwent either POPRC or SRC. Logistic regression was employed to identify predictors of POPRC usage.

To mitigate the impact of baseline differences on survival outcomes, a 1:2 propensity score matching (PSM) was applied. Kaplan-Meier curves and Log-rank tests were then utilized to assess the significance of overall survival (OS) differences between SRC and POPRC groups. Additionally, subgroup analysis based on predetermined indicators was conducted.

About 2,193 patients were included with a median follow-up of 53 months, of whom 233 (10.6%) received POPRC and 1,960 (89.4%) received SRC. No definitive predictors of POPRC were identified. Before PSM, POPRC resulted in a comparable OS to SRC (HR = 1.09, P = 0.309).

However, after PSM, POPRC was associated with significantly worse OS (HR = 1.23, P = 0.038). In subgroup analyses, POPRC showed non-inferior OS in patients with non-muscle invasive bladder cancer (NMIBC) (HR = 1.18, 95%CI 0.71-1.95, P = 0.531) and T2 patients (HR = 1.07, P = 0.669), but significantly worse OS in T3 patients (HR = 1.41, P = 0.02).

The study concluded that while POPRC currently does not involve strict screening, candidates for POPRC should be subject to more stringent criteria in the future to ensure satisfactory oncological outcomes. However, due to flaws in the study, additional evidence is needed to support these findings.

The study received no funds.

Source: https://pubmed.ncbi.nlm.nih.gov/39182105/

Wang C, Zhang X. (2024). “Pelvic organ-preserving radical cystectomy versus standard radical cystectomy in female patients diagnosed with bladder cancer.” World J Surg Oncol. 2024;22(1):218. Published 2024 Aug 24. doi:10.1186/s12957-024-03502-6

Role of TROAP in RCC Prognosis and Treatment Outcomes

KEY TAKEAWAYS

  • The study aimed to investigate the prognostic significance and therapeutic implications of TROAP across different subtypes of RCC.
  • Researchers found that elevated TROAP levels signify aggressive RCC and therapy resistance.

Trophinin Associated Protein (TROAP) has been implicated in various tumors; however, its role in renal cell carcinoma (RCC) remains largely unexplored.

Qinglin Tan and the team aimed to investigate the prognostic and therapeutic significance of TROAP in RCC, covering multiple subtypes.

Researchers first analyzed TROAP expression across various tumors using data from the TCGA pan-cancer cohort. They then assessed TROAP’s prognostic value in three TCGA RCC cohorts and a local cohort.

To further explore TROAP’s role, they performed functional enrichment analysis, examined somatic mutations and copy number variations, evaluated therapeutic response, and conducted in vitro experiments to investigate TROAP’s biological characteristics.

The results showed that TROAP was a negative factor in TCGA RCC datasets and the local cohort. Functional enrichment and in vitro experiments showed that TROAP acts as an oncogene, promoting tumor growth. The link between TROAP expression and gene mutations in RCC seems minimal. Moreover, high TROAP levels are linked to lower effectiveness of RCC treatments, including nivolumab and everolimus.

The study concluded that TROAP is a crucial RCC biomarker for prognosis and therapy response. High TROAP expression indicates aggressive tumor behavior and resistance to conventional treatments, highlighting its potential as a target for personalized RCC therapies.

The study was funded by the Guangdong Basic and Applied Basic Research Foundation.

Source: https://pubmed.ncbi.nlm.nih.gov/39153983/

Tan Q, Kong P, Chen G, et al. (2024). “Evaluating trophinin associated protein as a biomarker of prognosis and therapy response in renal cell carcinoma.” BMC cancer, 24(1), 1021. https://doi.org/10.1186/s12885-024-12802-9

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