The single-cell evolution trajectory presented different hypoxia heterogeneity to reveal the carcinogenesis of genes in clear cell renal cell carcinoma: Based on multiple omics and real experimental verification.

INTRODUCTION: Clear cell renal cell carcinoma (ccRCC) is the most prevalent and aggressive subtype of renal cell carcinoma, originating from renal tubular epithelial cells in the kidney. Hypoxia proves to be a feature commonly observed in solid tumors, leading to increased resistance to treatment and tumor progression. METHODS: scRNA-seq data were procured from GSE159115 data set. We utilized UMAP and NMF algorithm for clustering and dimensionality reduction. The FindAllMarkers function was used to compare various groups and identify potential hypoxia marker genes. A series of in vitro experiments, including CFA, flow cytometry targeting cell cycle, CCK-8, and EDU, was applied to investigate how ANGPTL4 regulated the ccRCC progression. Two cell lines of ccRCC cells, 786-O and Caki, were used for si-ANGPTL4 transfection. RESULTS: We annotated a total of a total of 6 cell clusters, namely ccRCC malignant cells, T cells, endothelial cells, myeloid cells, smooth muscle cells, and B cells. We observed higher levels of hypoxia-score in the ccRCC malignant cells, while lowest hypoxia-score in T and B cells. We detected multiple hypoxia-related subclusters of TME cells in ccRCC, among which S100A4 CD8+ T cells and nonhypoxia CD8+ T cells were found with a marked elevation of T cell inhibitory gene score. We identified that ANGPTL4+ endothelial cells might function as an integrative role in tumor angiogenesis. Multiple TME subclusters showed high potency in stratification of the prognosis of ccRCC patients. Moreover, by a series of in vitro experiment, we found ANGPTL4 regulated the ccRCC cell proliferation, probably through ERK/P38 pathway. CONCLUSION: We discerned multiple hypoxia-related subclusters of TME cells in ccRCC, which displayed distinct functional features and great potency in predicting prognosis of ccRCC patients. We identified the role of ANGPTL4 in regulating ccRCC proliferation via ERK/p38 pathway.

CircLRP6 contributes to prostate cancer growth and metastasis by binding to miR-330-5p to up-regulate NRBP1.

BACKGROUND: Circular RNA low-density lipoprotein receptor-related protein 6 (circLRP6) is considered as an oncogene in many types of cancers. However, the function and mechanisms of circLRP6 in prostate cancer (PCa) tumorigenesis remain largely undefined. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were conducted to assess the expression of circLRP6, microRNA (miR)-330-5p, and nuclear receptor binding protein 1 (NRBP1). Cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EDU) incorporation, flow cytometry, transwell, wound healing, and western blot assays were performed to detect cell proliferation, apoptosis, and metastasis in vitro. Subcutaneous tumor growth was observed in nude mice to investigate the role of circLRP6 in vivo. The targeting relationship between miR-330-5p and NRBP1 or circLRP6 was verified using dual-luciferase reporter, pull-down, and RNA immunoprecipitation (RIP) assays. Immunohistochemistry was employed to test relative protein expression. RESULTS: CircLRP6 was highly expressed in PCa tissues and cells, knockdown of circLRP6 impaired PCa cell growth and metastasis in vitro by affecting cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT). Mechanistic studies showed that circLRP6 could competitively bind with miR-330-5p to prevent the degradation of its target gene NRBP1. Rescue assay suggested that miR-330-5p inhibition reversed the inhibitory effects of circLRP6 knockdown on PCa cell growth and metastasis. Moreover, overexpression of miR-330-5p suppressed PCa progression via NRBP1. Notably, tumor formation assay indicated that circLRP6 silencing impeded tumor growth and EMT in vivo. CONCLUSION: Our findings demonstrated that circLRP6 promoted PCa tumorigenesis and metastasis through miR-330-5p/NRBP1 axis, suggesting a potential therapeutic target for PCa.

Giant Prostate Abscess: A Case Report and Literature Review.

Prostate abscess, a rare condition often associated with prostate bacterial infections, often occurs in immunosuppressive individuals and manifests as fever and lower urinary tract symptoms. Clinical practice lacks standardized diagnostic and treatment protocols for prostate abscesses, resulting in predominantly empirical approaches with uncertain outcomes. This study presents a case of a giant prostate abscess, diagnosed in a patient exhibiting fever, lower urinary tract symptoms (including dysuria, urinary frequency, urgency, and weakness), and anal pain. The diagnosis was confirmed through prostate magnetic resonance imaging and transrectal color ultrasound examinations. Treatment included targeted anti-infective therapy (based on the urine culture results), urine flow diversion (suprapubic bladder puncture stomy), ultrasound-guided perineal puncture drainage of the prostatic abscess, intermittent abscess cavity irrigation, and urethral electroprostatectomy. The patient experienced a complete recovery and significantly improved quality of life. This successful case underscores several key points: (1) the importance of targeted anti-infective therapy based on etiological findings in prostate abscess treatment; (2) early urine flow diversion, precise puncture drainage, and intermittent abscess cavity irrigation may be one of crucial elements in abscess management; (3) the potential significance of transurethral prostate resection following abscess resolution in preventing recurrence. It is hoped that this case report offers new valuable insights for diagnosing and treating prostate abscesses. Slightly different from previous treatment experience, we extra used early urine diversion, intermittent abscess cavity irrigation, and etiological electroprostatectomy, which might also hold promise as potential therapies.

Association between radiotherapy and prognosis in patients with small cell carcinoma of the bladder undergoing bladder-sparing surgery.

Background: Small cell carcinoma of the bladder is rare and has a poor prognosis. This study aimed to investigate whether radiotherapy after bladder-sparing surgery could improve the survival benefits of patients. Methods: This population-based retrospective cohort study used data from the Surveillance, Epidemiology, and End Results cohort in the United States to investigate small cell carcinoma of the bladder. Univariate and multivariate Cox regression analyses were used to identify significant risk factors influencing the clinical prognosis. A propensity score matching (PSM) algorithm was used to reduce the interference of confounding factors in each study group. The matched groups underwent Kaplan-Meier survival analysis to assess the potential survival benefits. Results: Univariate regression analysis demonstrated that age (P<0.001), tumour stage (T stage) (P=0.005), node stage (N stage) (P<0.001), chemotherapy (P<0.001), bone metastasis (P<0.001), liver metastasis (P<0.001), lung metastasis (P=0.005), tumour size (P=0.005), and radiotherapy (P<0.001) were related factors affecting survival. Multivariate regression analysis revealed that age (P=0.001), T stage (P=0.054), N stage (P<0.001), radiotherapy (P=0.010), chemotherapy (P<0.001), bone metastasis (P=0.007), and liver metastasis (P<0.001) were independent factors affecting survival. Moreover, survival analysis was performed on the PSM-matched groups, leading to the following findings: (1) the radiotherapy group exhibited a superior survival prognosis compared with the non-radiotherapy group (P<0.001); (2) the survival prognosis of individuals who underwent radiotherapy and chemotherapy was higher than that of those who underwent chemotherapy alone (P<0.001). Conclusion: The findings of this study suggest that radiotherapy improves survival benefits for patients with small cell carcinoma of the bladder who undergo bladder-sparing surgery. Furthermore, radiotherapy combined with chemotherapy demonstrates a greater survival benefit compared with chemotherapy alone. The results underscore the importance of considering radiotherapy as a valuable treatment option for such patients, highlighting its potential benefits in improving their overall prognosis.