A tumor-associated macrophages related model for predicting biochemical recurrence and tumor immune environment in prostate cancer.

OBJECTIVE: To identify tumor-associated macrophages (TAMs) related molecular subtypes and develop a TAMs related prognostic model for prostate cancer (PCa). METHODS: Consensus clustering analysis was used to identify TAMs related molecular clusters. A TAMs related prognostic model was developed using univariate and multivariate Cox analysis. RESULTS: Three TAMs related molecular clusters were identified and were confirmed to be associated with prognosis, clinicopathological characteristics, PD-L1 expression levels and tumor microenvironment. A TAMs related prognostic model was constructed. Patients in low-risk group all showed a more appreciable biochemical recurrence-free survival (BCRFS) than patients in high-risk group in train cohort, test cohort, entire TCGA cohort and validation cohort. SLC26A3 attenuated progression of PCa and prevented macrophage polarizing to TAMs phenotype, which was initially verified. CONCLUSIONS: We successfully identified molecular clusters related to TAMs. Additionally, we developed a prognostic model involving TAMs that exhibits excellent predictive performance for biochemical recurrence-free survival in PCa.

ND630 controls ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003.

BACKGROUND: ND630 is believed to be a new therapy pharmacologic molecule in targeting the expression of ACACA and regulating the lipid metabolism. However, the function of ND630 in prostate cancer remains unknown. KIF18B, as an oncogene, plays a vital role in prostate cancer progression. circKIF18B_003 was derived from oncogene KIF18B and was markedly overexpressed in prostate cancer tissues. We speculated that oncoprotein KIF18B-derived circRNA circKIF18B_003 might have roles in prostate cancer promotion. The aim of this study was to validate whether ND630 could control ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003. METHODS: RT-qPCR was used to analyze the expression of circKIF18B_003 in prostate cancer cell lines and prostate cancer samples. circKIF18B_003 expression was modulated in prostate cancer cells using circKIF18B_003 interference or overexpression plasmid. We examined the function and effects of circKIF18B_003 in prostate cancer cells using CCK-8, colony formation, wound healing, and Transwell invasion assays and xenograft models. Fluorescence in situ hybridization (FISH) was performed to evaluate the localization of circKIF18B_003. RNA immunoprecipitation (RIP), RNA pull down, and luciferase reporter assay were performed to explore the potential mechanism of circKIF18B_003. RESULTS: The function of ND630 was determined in this study. circKIF18B_003 was overexpressed in prostate cancer tissues, and overexpression of circKIF18B_003 was associated with poor survival outcome of prostate cancer patients. The proliferation, migration, and invasion of prostate cancer cells were enhanced after up-regulation of circKIF18B_003. circKIF18B_003 is mainly located in the cytoplasm of prostate cancer cells, and the RIP and RNA pull down assays confirmed that circKIF18B_003 could act as a sponge for miR-370-3p. Further study demonstrated that up-regulation of circKIF18B_003 increased the expression of ACACA by sponging miR-370-3p. The malignant ability of prostate cancer cells enhanced by overexpression of circKIF18B_003 was reversed by the down-regulation of ACACA. We found that overexpression of circKIF18B_003 was associated with lipid metabolism, and a combination of ND-630 and docetaxel markedly attenuated tumor growth. CONCLUSION: ND630 could control ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003. ND630 and circKIF18B_003 may represent a novel target for prostate cancer.

Machine learning-based autophagy-related prognostic signature for personalized risk stratification and therapeutic approaches in bladder cancer.

OBJECTIVE: Bladder cancer (BCa) is a highly lethal urological malignancy characterized by its notable histological heterogeneity. Autophagy has swiftly emerged as a diagnostic and prognostic biomarker in diverse cancer types. Nonetheless, the currently accessible autophagy-related signature specific to BCa remains limited. METHODS: A refined autophagy-related signature was developed through a 10-fold cross-validation framework, incorporating 101 combinations of machine learning algorithms. The performance of this signature in predicting prognosis and response to immunotherapy was thoroughly evaluated, along with an exploration of potential drug targets and compounds. In vitro and in vivo experiments were conducted to verify the regulatory mechanism of hub gene. RESULTS: The autophagy-related prognostic signature (ARPS) has exhibited superior performance in predicting the prognosis of BCa compared to the majority of clinical features and other developed markers. Higher ARPS is associated with poorer prognosis and reduced sensitivity to immunotherapy. Four potential targets and five therapeutic agents were screened for patients in the high-ARPS group. In vitro and vivo experiments have confirmed that FKBP9 promotes the proliferation, invasion, and metastasis of BCa. CONCLUSIONS: Overall, our study developed a valuable tool to optimize risk stratification and decision-making for BCa patients.

Subtype and prognostic analysis of immunogenic cell death-related gene signature in prostate cancer.

Background: Immunogenic cell death (ICD) plays a vital role in tumor progression and immune response. However, the integrative role of ICD-related genes and subtypes in the tumor microenvironment (TME) in prostate cancer (PCa) remains unknown. Materials and methods: The sample data were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Memorial Sloan Kettering Cancer Center (MSKCC) prostate cancer-related databases. We first divided the subtypes based on ICD genes from 901 PCa patients and then identified the prognosis- related genes (PRGs) between different ICD subtypes. Subsequently, all the patients were randomly split into the training and test groups. We developed a risk signature in the training set by least absolute shrinkage and selection operator (LASSO)-Cox regression. Following this, we verified this prognostic signature in both the training test and external test sets. The relationships between the different subgroups and clinical pathological characteristics, immune infiltration characteristics, and mutation status of the TME were examined. Finally, the artificial neural network (ANN) and fundamental experiment study were constructed to verify the accuracy of the prognostic signature. Results: We identified two ICD clusters with immunological features and three gene clusters composed of PRGs. Additionally, we demonstrated that the risk signature can be used to evaluate tumor immune cell infiltration, prognostic status, and an immune checkpoint inhibitor. The low-risk group, which has a high overlap with group C of the gene cluster, is characterized by high ICD levels, immunocompetence, and favorable survival probability. Furthermore, the tumor progression genes selected by the ANN also exhibit potential associations with risk signature genes. Conclusion: This study identified individuals with high ICD levels in prostate cancer who may have more abundant immune infiltration and revealed the potential effects of risk signature on the TME, immune checkpoint inhibitor, and prognosis of PCa.

The effect of body mass index on quality of life in modified single stoma cutaneous ureterostomy or ileal conduit after radical cystectomy.

OBJECTIVE: To explore the influence of postoperative body mass index (BMI) change on postoperative quality of life (QOL) in patients undergoing radical cystectomy (RC) plus modified single stoma cutaneous ureterostomy (MSSCU) or ileal conduit (IC). METHODS: Patients were divided into two groups according to different BMI change patterns: patients experiencing an elevated postoperative BMI level, along with a clinically significant increase in their BMI (an increase of more than 10%) were categorized as Group 1, while patients experiencing a decrease postoperative BMI level, along with a clinically significant reduction in their BMI (a decrease of more than 5%) were categorized as Group 2. Spearman correlation analysis was used to examine the correlations between quality-of-life scores and postoperative clinical parameters. RESULTS: Spearman correlation analysis showed that postoperative BMI, late complications and catheter-free state were significantly associated with postoperative global QoL and symptom scale in MSSCU and postoperative global QoL and physical scale in IC patients. Additionally, postoperative BMI, catheter-free state and the use of adjuvant therapy were associated with bad performance in many scales of QoL like body image, future perspective, social scale, future perspective (MSSCU), and abdominal bloating (IC) (Table 2, p<0.05). Patients in Group 2 with significant weight loss had a better Global QoL, a lower rate of stomal stricture and a higher catheter-free state compared with those in Group 1 in both IC and MSSCU patients. MSSCU patients in Group 2 could achieve a comparable Global QoL as to IC patients in Group 1. CONCLUSION: Controlling the substantial increase in body weight after surgery contributes to improving QoL, reducing the occurrence of stomal stricture, and ensuring a postoperative catheter-free state in BCa patients undergoing MSSCU.