Tissue‐derived extracellular vesicles (Ti‐EVs) play a crucial role in tumour progression, but their value as differential diagnostic markers for various renal cell carcinoma (RCC) subtypes remains uncertain. Through analysis of paired tumour and normal tissues, along with their corresponding Ti‐EVs, we identified NEAT1 and MMP15 as markers for papillary RCC (pRCC); DSG2 and AC026888.1 for chromophobe RCC (chRCC); NDUFA4L2, SERPINA1, VEGFA, EGLN3, CPE and C6orf223 for low‐grade clear cell RCC (low‐grade ccRCC); and NDUFA4L2, APOC1, TGFBI and LINC00887 for high‐grade ccRCC (high‐grade ccRCC). In an external validation cohort, an area under the curve (AUC) of 0.922 for low‐grade ccRCC detection and 0.874 for high‐grade ccRCC detection was achieved, respectively, using urinary EVs. Furthermore, integrating single‐cell sequencing data revealed that SERPINA1 and VEGFA in low‐grade ccRCC, and APOC1 and TGFBI in high‐grade ccRCC, were derived from tumour‐associated macrophages, whereas NDUFA4L2 originated from cancer cells in both low‐ and high‐grade ccRCC.

The role of cystathionine γ-lyase (CTH) in the prognosis and immune invasion of hepatocellular carcinoma (HCC) remains poorly understood. In this study, the clinical data of patients with HCC were analyzed, and the expression level of CTH was compared between HCC and normal tissues using the R package and various databases. We found that CTH expression was significantly decreased in HCC compared with normal tissues, and its expression was associated with various clinicopathological factors, including tumor stage, gender, tumor status, residual tumor, histologic stage, race, alpha-fetoprotein (AFP), albumin, drinking, and smoking. Our results suggest that CTH might be a protective factor for the survival of patients with HCC. Further functional analysis revealed that high CTH expression was enriched in the Reactome signaling by interleukins and the Reactome neutrophil degranulation. Moreover, CTH expression was closely correlated with a variety of immune cells, including a negative correlation with the CD56 (bright) NK cells and follicular helper T cell (TFH), while a positive correlation with Th17 cells and central memory T cell (Tcm). High expression of CTH in immune cells predicted a better prognosis of HCC. Our findings further indicated Pyridoxal phosphate, l-cysteine, Carboxymethylthio-3-(3-chlorophenyl)-1,2,4-oxadiazol, 2-[(3-Hydroxy-2-Methyl-5-Phosphonooxymethyl-Pyridin-4-Ylmethyl)-Imino]-5-phosphono-pent-3-enoic acid and L-2-amino-3-butynoic acid as potential target candidate medications for HCC treatment based on CTH. Our study suggests that CTH can serve as a biomarker to predict the prognosis and immune infiltration of HCC.

Objectives: To identify causal genes for benign prostatic hyperplasia (BPH) based on single-cell RNA sequencing (scRNA-seq) and genome-wide association studies. Methods: We explored scRNA-seq datasets to identify the differentially expressed genes (DEGs) in BPH patients vs. healthy controls. Mendelian randomization (MR) was conducted to investigate the causal relationships between the identified DEGs and BPH. Bayesian colocalization and reverse MR were performed to consolidate the MR findings. Potential therapeutic drugs targeting causal genes were explored via molecular docking. The results of bioinformatics analyses were validated through experiments including flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence staining. Results: BPH patients showed an increased proportion of myeloid cells in the prostate transition zone, with 85 classical monocyte-specific DEGs. Among these, SLC25A37 was causally associated with BPH based on MR, Bayesian colocalization, and reverse MR analyses. Functional analyses indicated its involvement in proliferation-related signaling pathways in classical monocytes. Ferriheme chloride and catechol were identified as potential drugs targeting SLC25A37. In vitro study confirmed increased expression levels of SLC25A37 and myeloid cells in BPH tissues. Conclusions: Our integrative analyses revealed SLC25A37 as a novel causal gene in BPH pathogenesis, unveiling potential therapeutic strategies for BPH treatment.

PurposeThe role of cystathionine γ-lyase (CTH) in the prognosis and immune invasion of hepatocellular carcinoma (HCC) has not been reported.MethodsCombined with the clinical characteristics of HCC, CTH was analyzed via R package and various databases in this study.ResultsCompared with normal tissues, the level of CTH in HCC was significantly decreased, the extent of which was related to tumor clinicopathologic stage, gender, tumor status, residual tumor, histologic stage, race, alpha-fetoprotein (AFP), albumin, drinking and smoking. The results suggested that CTH might be a protective factor for the survival of HCC patients. Further functional analysis showed that the high expression of CTH was enriched in the reactome signaling by interleukins and the reactome neutrophil degranulation. Moreover, the expression of CTH was negatively correlated with the CD56 (bright) NK cells and Follicular helper T cell (TFH), positively correlated with Th17 cells and central memory T cell (Tcm), and closely correlated with the gene markers of a variety of immune cells. Also, high expression of CTH based on immune cells predicted the better prognosis of HCC. Pyridoxal phosphate, L-cysteine, Carboxymethylthio-3-(3-chlorophenyl)-1,2,4-oxadiazol, 2-[(3-Hydroxy-2-Methyl-5-Phosphonooxymethyl-Pyridin-4-Ylmethyl)-Imino]-5-phosphono-pent-3-enoic acid and L-2-amino-3-butynoic acid may be the targeted candidate medications for the treatment of CTH in HCC.ConclusionIn brief, CTH can be used as a biomarker to predict the prognosis and immune infiltration of HCC.