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RELATED :Bladder Cancer:Prostate Cancer:RCC (Renal Cell Carcinoma)

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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

KRT23 Identified as Key Target in BLCA Immunotherapy

KEY TAKEAWAYS

  • The study aimed to investigate multiple immune checkpoint gene profiles in BLCA to identify potential immunotherapy targets like KRT23.
  • Researchers identified KRT23 as a key target for improving immunotherapy in BLCA.

In recent decades, significant progress has been made in treating bladder cancer (BLCA), particularly with the development of immune checkpoint inhibitors (ICIs). However, most studies have focused on individual ICIs, with limited research addressing the comprehensive gene expression profiles of multiple immune checkpoints. Understanding the broader landscape of immune checkpoint genes is crucial for optimizing immunotherapy strategies and improving patient outcomes.

Dongshan Chen and the team aimed to assess the expression profiles of multiple immune checkpoint genes in BLCA, explore their relationship with the tumor immune microenvironment, and identify key targets for enhancing immunotherapy, with a specific focus on KRT23.

They performed an inclusive analysis using RNA-sequencing profiling data and clinical information from patients with BLCA and normal human bladder samples, sourced from the Cancer Genome Atlas and Gene Expression Omnibus databases.

The data were analyzed to identify differential expression profiles of immune checkpoint genes (ICGs) following consensus clustering analysis. From 526 intersecting differentially expressed genes, LASSO Cox regression analysis was applied to develop an ICG signature, enabling further investigation of immune infiltration and potential therapeutic targets.

Based on the expression of ICGs, patients with BLCA were classified into 3 distinct subtypes, each exhibiting unique phenotypic and mechanistic characteristics. Furthermore, the developed ICG signature was identified as an independent predictor of outcomes in patients with BLCA and was closely associated with immune infiltration, ICG expression levels, and chemotherapy effectiveness.

The study concluded that a systematic and comprehensive analysis of immune checkpoint gene expression led to the establishment of the ICG signature, which revealed significant differences in ICG expression and the tumor immune microenvironment.

This information aids in risk stratification and supports the advancement of precision medicine for BLCA. Furthermore, KRT23 was identified as the most critical model gene, highlighting its potential as a promising target to enhance immunotherapy in patients with BLCA.

The study received no funds.

Source: https://pubmed.ncbi.nlm.nih.gov/39160525/

Chen D, Cao H, Zheng X, et al. (2024). “Immune checkpoint gene signature assesses immune infiltration profiles in bladder cancer and identifies KRT23 as an immunotherapeutic target.” BMC Cancer. 2024;24(1):1024. Published 2024 Aug 19. doi:10.1186/s12885-024-12790-w

Impact of QoL and Optimism on Prognostic Views in mRCC and mBC

KEY TAKEAWAYS

  • The study aimed to evaluate perceptions of treatment outcomes in patients with mRCC and mBC, focusing on the role of optimism and QoL.
  • Most patients with mRCC and mBC had inaccurate views on treatment outcomes, linked to higher QoL and optimism.

Durable complete response rates for metastatic renal cell carcinoma (mRCC) and metastatic bladder cancer (mBC) remain low despite advancements in therapy. Palliative care prioritizes life extension and improving quality of life (QoL) rather than a cure.

Hatice Bolek and the team aimed to examine how patients with mRCC and mBC perceive treatment outcomes and how QoL and optimism impact these perceptions.

Between March 15, 2023, and January 15, 2024, researchers conducted a multicenter, cross-sectional online survey targeting patients diagnosed with mRCC and mBC. The survey included structured questions assessing perceptions of disease cure, symptom improvement, daily activity performance, and life extension from treatment.

To measure optimism and QoL, the European Organization for Research and Treatment of Cancer 30.3 QoL questionnaire and the Life Orientation Test were used. The study revealed high optimism and inaccurate beliefs about cure among patients.

About 169 patients participated in the survey, with the majority rating their general health as good (72.2%) and excellent (13.6%). Patients who rated their health as good-excellent had higher median general QoL and optimism scores than those who rated it fair-poor. Overall, 85.2% of patients believed the possibility of a cure was very likely or likely.

Most participants thought treatment would relieve symptoms (30.2% very likely, 49.1% likely), improve daily activity performance (28.4% very likely, 55.6% likely), and extend life (32.5% very likely, 53.3% likely). Patients who responded very likely and likely to these questions had higher QoL and optimism scores than those who responded a little likely or not possible.

The study concluded that most patients with mRCC and mBC held inaccurate beliefs about treatment outcomes. Higher QoL and optimism were linked to greater inaccuracies in these perceptions.

Funding is provided by Roche, Novartis, BMS, Merck, AstraZeneca, Nektar, Johnson &Johnson, Lilly, Amgen, Incyte, Bayer, Yuhan, Henlius, Pfizer, Biontech, Genmab, Beigene, GSK.

Source: https://pubmed.ncbi.nlm.nih.gov/39208383/

Bolek H, Arslan C, Basaran M, et al. (2024). “Perceptions and Expectations: A Study on Prognostic Perception and Quality of Life in Patients With Metastatic Renal and Bladder Cancer.” JCO Glob Oncol. 2024;10:e2400201. doi:10.1200/GO.24.00201

Low HALP Scores Predict Bladder Cancer Recurrence After UTUC

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

ScRNA-seq Identifies M2 Macrophage Markers for PCa Prognosis

KEY TAKEAWAYS

  • The study aimed to investigate the prognostic value of M2 macrophages and their associated markers in PCa.
  • Researchers noticed that M2 macrophages and their associated genes are crucial predictors of PCa progression and metastasis.

Prostate cancer (PCa) is the highest malignant tumor among men globally, with the tumor microenvironment (TME) playing a critical role in tumor growth. M2 macrophages are implicated in the progression of various solid tumors, including PCa.

Yitian Ou and the team aimed to assess the role of M2 macrophages and their associated genes in predicting the occurrence, development, and metastasis of PCa.

They performed an inclusive analysis using Single-cell RNA-seq (scRNA-seq) and mRNA expression data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Quality control, normalization, reduction, clustering, and cell annotation of scRNA-seq data were conducted using the Seurat package.

Tumor-associated macrophages (TAMs) were analyzed to identify sub-populations and marker genes specific to M2 macrophages. Differentially expressed genes (DEGs) in PCa were determined with limma, and immune infiltration was assessed using CIBERSORTx.

A weighted correlation network analysis (WGCNA) was performed to identify M2 macrophage-related modules and genes. Marker genes from scRNA-seq data and hub genes from WGCNA were integrated to develop a prognostic gene signature using Univariate and LASSO regression analyses.

The risk score was calculated, and DEGs, biological functions, and immune characteristics related to the risk score were explored. Additionally, a predictive nomogram was constructed, and CCK8, Transwell, and wound healing assays were employed to validate cell phenotype changes in co-cultured patients.

About 2,431 marker genes of M2 macrophages and 650 hub M2 macrophage-related genes were identified through scRNA-seq data and WGCNA. An overlap of scRNA-seq data and WGCNA results yielded 113 M2 macrophage-related genes. Nine M2 macrophage-related genes (SMOC2, PLPP1, HES1, STMN1, GPR160, ABCG1, MAZ, MYC, and EPCAM) were selected as prognostic gene signatures.

The M2 risk score was calculated, and DEGs, immune scores, stromal scores, ESTIMATE scores, tumor purity, immune cell infiltration, immune checkpoint expression, and responses to immunotherapy and chemotherapy were assessed. Additionally, a predictive nomogram was constructed. CCK8, Transwell invasion, and wound healing assays further confirmed that M2 macrophages promoted the proliferation, invasion, and migration of PCa (P < 0.05).

The study concluded that M2 macrophages and their associated genes are crucial in promoting the occurrence, development, and metastasis of PCa, serving as reliable predictors for the disease.

The study was funded by the Natural Science Foundation of China (No. 81860453), the Yunnan Provincial Major Science and Technology Projects (No. 2018ZF009), and the Top Physician Project of Yunnan 2019. The Scientific Research Foundation Project of Yunnan Provincial Department of Education (2022Y195), and the Project of Yunnan Provincial Science and Technology (202301AT070321, 202201AY070001-119).

Source: https://pubmed.ncbi.nlm.nih.gov/39221762/

Ou Y, Xia C, Ye C, et al. (2024). “Comprehensive scRNA-seq analysis to identify new markers of M2 macrophages for predicting the prognosis of prostate cancer.” Ann Med. 2024;56(1):2398195. doi:10.1080/07853890.2024.2398195

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

Examining Prostate Cancer Mortality in NRW: 2007-2021

KEY TAKEAWAYS

  • The study aimed to investigate the mortality trends and age-specific risks in patients with prostate cancer.
  • Researchers noticed that prostate cancer deaths in NRW are rising with age but not increasing in age-specific risk; further investigation is ongoing.

Prostate cancer mortality rates in Germany exceed the international average, although age-standardized mortality and years of life lost per capita are decreasing. This study examines mortality-related measures specific to North Rhine-Westphalia (NRW).

Kevin Claaßen and the team aimed to assess the trends in prostate cancer mortality in NRW, focusing on changes in age-specific risks and the impact of demographic aging on mortality rates.

They performed an inclusive analysis using cause-of-death statistics and data from the NRW State Cancer Registry, covering 45,300 deaths from 2007 to 2021. Mortality rates, lifetime mortality risk from prostate cancer, median age at death, and years of life lost were calculated. Additionally, the study reported the 15 most frequent causes of death among 95,013 patients diagnosed with prostate cancer.

The study reveals that with a stable lifetime mortality risk from prostate cancer, age-standardized mortality and years of life lost per capita are decreasing, while crude mortality and median age at death are increasing in NRW. Less than half of the patients die from their prostate cancer. Additionally, cancers of the urinary bladder and other urinary organs occur more frequently as a cause of death than would be expected based on the age-specific risk in the total population.

The study concluded that the rise in prostate cancer deaths in NRW is primarily due to demographic aging, with no increase in age-specific mortality risk and deaths occurring at progressively older ages. Additionally, a significant association with lower urinary tract cancers in patients diagnosed with prostate cancer was identified, warranting further investigation.

The study received no funds.

Source: https://pubmed.ncbi.nlm.nih.gov/39192311/

Claaßen K, Karpinski M, Kajüter H, et al. Mortality from prostate cancer in the years 2007-2021 in North Rhine-Westphalia, Germany. BMC Urol. 2024;24(1):181. Published 2024 Aug 27. doi:10.1186/s12894-024-01564-y

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