Deep vein thrombosis (DVT) is among the most frequent complications of surgery. This study aimed to analyse the incidence and risk factors of lower extremity venous thrombosis after urologic surgery. This prospective two-centre study was conducted from August 2019 to January 2020. Patients who underwent urological procedures were enrolled. The primary endpoint was the detection of asymptomatic or symptomatic DVT of the lower extremity within 7 days after surgery. Univariate and least absolute shrinkage and selection operator (LASSO) logistic regression analyses were performed. Fifty-six of 1011 patients developed DVT. In the univariate analysis, Barthel Index ≤40, d-dimer level ≥0.5 mg/L and age ≥60 years (p < 0.001) were identified as the most significant risk factors. The LASSO logistic regression model identified nine factors: age, history of DVT, lymph node dissection, perioperative steroid use, Caprini score, Barthel Index, D-dimer level, cystectomy, and prostatectomy. Our study used the LASSO logistic regression model to provide reliable data on the risk factors for DVT after comprehensive urologic surgery. The incidence of DVT in this group was 5.54%. This might facilitate individualised anticoagulant management in patients undergoing urological procedures.

While cancer-associated fibroblasts (CAFs) in the tumour microenvironment may play important roles in bladder cancer (BCa) progression, their impacts on BCa chemoresistance remain unclear. Using human BCa samples, we found that tumour tissues possessed more CAFs than did adjacent normal tissues. Both the presence of CAFs in the BCa stroma and the expression of ERβ in BCa contribute to chemoresistance, and CAFs and BCa cells interact to affect ERβ expression. In vitro co-culture assays demonstrated that compared with normal bladder cells, BCa cells had a higher capacity to induce the transformation of normal fibroblasts into CAFs. When BCa cells were co-cultured with CAFs, their viability, clone formation ability and chemoresistance were increased, whereas their apoptotic rates were downregulated. Dissection of the mechanism revealed that the recruited CAFs increased IGF-1/ERβ signalling in BCa cells, which then led to the promotion of the expression of the anti-apoptotic gene Bcl-2. Blocking IGF-1/ERβ/Bcl-2 signalling by either an shRNA targeting ERβ or an anti-IGF-1 neutralizing antibody partially reversed the capacity of CAFs to increase BCa chemoresistance. The in vivo data also confirmed that CAFs could increase BCa cell resistance to cisplatin by increasing ERβ/Bcl-2 signalling. The above results showed the important roles of CAFs within the bladder tumour microenvironment, which could enhance BCa chemoresistance.

Background: As a transcription factor, Zinc finger protein ZIC2 can interact with various DNAs and proteins. Current studies have shown that ZIC2 plays an oncogene role in various cancers. In this study, we systematically characterize the prevalence and predictive value of ZIC2 expression across multiple cancer types.Methods: We mined several public databases, including Oncomine, the Cancer Genome Atlas (TCGA), cBioPortal, Kaplan-Meier Plotter and PrognoScan to evaluated the differentially expressed ZIC2 between tumor samples and normal control samples in pan-cancner, and then explored the association between ZIC2 expression and patient survival, prognosis and clinicopathologic stage. We also analyzed the relationship between tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment, tumor- and immune-related genes and ZIC2 expression. Finally, we explored the potential signaling pathway mechanism through gene set enrichment analysis (GSEA).Results: ZIC2 expression was higher in most cancer tissues compared with adjacent normal tissues. High ZIC2 expression was associated with worse prognosis and a higher clinicopathologic stage. ZIC2 expression was strongly associated with the TMB, MSI, tumor microenvironment and tumor- and immune-related genes. The GSEA revealed that multiple tumor- and immune-related pathways were differentially enriched in ZIC2 high or low expression phenotype.Conclusion: ZIC2 expression may be a potential prognostic molecular biomarker of poor survival in pan-cancer and may act as an oncogene with a strong effect in the processes of tumorigenesis and progression.

Hyperglycemia is a recognized risk factor for bladder cancer (BC). Enfortumab vedotin (EV), the first NECTIN4-targeting antibody-drug conjugate, demonstrates promising clinical efficacy in patients with advanced BC. In this study, we show that EV treatment is less effective in BC patients with diabetes than in those with normoglycemia. The subsequent in vitro and in vivo experiments indicate that high glucose decreases the sensitivity of BC cells to EV. Mechanistically, lactate overproduction associated with high glucose promotes AARS1-mediated YTHDC1 lactylation and enhances RNF183-mediated YTHDC1 ubiquitination. Downregulated YTHDC1 reduces JUND mRNA stability in an m⁶A-dependent manner, subsequently decreasing NECTIN4 expression and EV responsiveness. Our study identifies a high-glucose-associated lactate-AARS1-YTHDC1-JUND-NECTIN4 axis that affects EV sensitivity in BC. Targeting this axis with JUND activators or β-alanine may offer therapeutic strategies to enhance the sensitivity of BC cells to EV.

Background: As a transcription factor, Zic family member 2 (ZIC2) has been involved in more and more studies of tumorigenesis, which has been proved by our research team to be an effective prognostic marker for Pan-cancer. However, the prognosis, tumor promoting effect and regulatory mechanism of ZIC2 in clear cell renal cell carcinoma (ccRCC) are still unknown.