Shouhua Pan

Objective: To compare postoperative infection-related characteristics and risk factors for systemic inflammatory response syndrome between asymptomatic and symptomatic ureteral stone patients undergoing ureteroscopy. Methods: This retrospective cohort study included 475 patients undergoing ureteroscopy for ureteral stones from May 2023 to August 2024. Patients were divided into asymptomatic (n = 85) and symptomatic (n = 390) groups. Clinical characteristics and inflammatory markers were compared, and multivariate logistic regression was used to identify independent risk factors for postoperative systemic inflammatory response syndrome. Results: The asymptomatic group had higher stone impaction rates, larger stone volumes, and longer operative time but lower inflammatory markers (all p < 0.05). The incidence of systemic inflammatory response syndrome was lower in the asymptomatic group. In the symptomatic group, independent risk factors for systemic inflammatory response syndrome included sex, urine culture, operative time, C-reactive protein, and systemic immune–inflammation index. In the asymptomatic group, only positive urine culture was identified as a risk factor. Conclusions: Asymptomatic ureteral stones are associated with a lower risk of postoperative systemic inflammatory response syndrome. However, positive urine culture remains a key predictor of postoperative infection and requires careful management.

Rationale: Urethral metastasis recurrence after surgery for urothelial carcinoma (UC) is a common clinical challenge, yet there is no established optimal treatment strategy to effectively control postoperative metastasis and recurrence. This case report evaluates the efficacy of total urethrectomy combined with adjuvant chemotherapy and PD-1 + antibody–drug conjugate (ADC) immunotherapy in managing UC urethral metastasis. Patient concerns: Three patients with a history of UC surgery presented with urethral metastasis recurrence, raising concerns about disease progression, treatment options, and long-term survival. Diagnoses: All 3 patients were definitively diagnosed with UC urethral metastasis recurrence based on clinical, imaging, and histopathological examinations. Interventions: Each patient underwent total urethrectomy followed by adjuvant chemotherapy and PD-1 inhibitor + ADC combination immunotherapy. Outcomes: Post-treatment follow-up, including serum tumor marker assessments and imaging studies, showed no significant recurrence. The patients exhibited prolonged overall survival and maintained a satisfactory postoperative quality of life. Lessons: Total urethrectomy combined with chemotherapy and PD-1+ADC immunotherapy may significantly improve outcomes in UC patients with postoperative urethral metastasis recurrence. This multimodal approach warrants further investigation in larger clinical studies.

Background Bladder cancer (BC), characterized by epithelial heterogeneity, remains a challenging malignancy with limited tissue biomarkers for anticipating neoadjuvant chemotherapy efficacy. Tumor progression, orchestrated by cancer cells, intricately involves the modulation of apoptosis-related pathways. Given their pivotal role in this cascade, apoptosis-related genes emerge as potential determinants of tumor development. Concurrently, the formidable challenge of drug resistance significantly impedes the success of cancer treatments, where a patient's susceptibility to chemotherapy profoundly influences therapeutic outcomes. Consequently, our objective is to develop a prognostic risk model rooted in apoptosis and chemotherapy related gene. This comprehensive approach aims to enhance our ability to predict the prognosis of BC patients and optimize treatment strategies. Methods We extracted 412 BC patients and 19 healthy humans RNA-seq samples from the TCGA database and loaded 1416 apoptosis and chemotherapy related genes from the GeneCards website. Subsequently, we established four risk score models for apoptosis and chemotherapy related genes through single-factor, multi-factor, and LASSO regression analysis. Additionally, we conducted analyses on the risk model using methods such as Kaplan–Meier log-rank test, principal component analysis, time-dependent ROC curve analysis, uni-variate analysis, and multivariate Cox regression analysis. We discussed the relationship of this model with the immune status and its predictive capability for drug sensitivity. Finally, we validated the correlation of these four genes with BC drug resistance by establishing drug-resistant cell lines and conducting in vitro drug resistance-related experiments. Results This study’s findings demonstrate that apoptosis and chemotherapy related genes can impact the progression of BC. We obtained a prognostic risk model composed of four apoptosis and chemotherapy related genes (FASN, GLI2, VHL, and PDGFRA). Among them, FASN, GLI2, and PDGFRA were identified as risk factors, with high expression in the high-risk group, while VHL exhibited high expression in the low-risk group. A nomogram was constructed based on these features to assess patient survival and prognosis. In addition, in vitro drug resistance experiments showed that FASN was associated with BC resistance. Conclusion These four apoptosis-related genes may serve as valuable factors for predicting the prognosis of BC, providing insights into the pathogenic mechanisms of apoptosis-related genes in BC. It provides a new research path to overcome drug resistance in BC. They offer more precise references and guidance for the treatment of high-risk BC patients.

Purpose Multiple epidemiological studies have demonstrated a correlation between the lipidome and bladder cancer (BC). Nonetheless, the current literature lacks consensus on the causal link between the lipidome and BC. We utilise a two-sample Mendelian randomisation approach to meticulously evaluate the causal link between the two variables. Methods A two-sample Mendelian randomisation (MR) analysis was performed utilising publically accessible genome-wide association research data. The principal technique utilised for the inquiry was the inverse variance-weighted (IVW) meta-analysis. Furthermore, Bayesian weighted Mendelian randomisation (BWMR) was employed to corroborate the findings. Supplementary validation was conducted utilising Cochran’s Q test and methodologies including MR-Egger. Results The two-sample MR analysis, in conjunction with BWMR analysis, revealed a correlation between the genetic prediction of the lipidome and the risk of BC. Sterol ester (SE) 27:1/16:0 (OR: 1.148, 95% CI: 1.020–1.293, p = 0.022), Sterol ester 27:1/20:3 (OR: 1.132, 95% CI: 1.006–1.274, p = 0.040), Phosphatidylcholine (PC) 18:0_20:3 (OR: 1.257, 95% CI: 1.101–1.436, p = 0.001), Sphingomyelin (SM) d38:1 (OR: 1.120, 95% CI: 1.016–1.235, p = 0.023), Sphingomyelin d40:2 (OR: 1.156, 95% CI: 1.033–1.295, p = 0.012), Triacylglycerol (TAG) 46:1 (OR: 1.178, 95% CI: 1.013–1.369, p = 0.034), Triacylglycerol 49:2 (OR: 1.219, 95% CI: 1.031–1.442, p = 0.021), Triacylglycerol 50:5 (OR: 1.173, 95% CI: 1.038–1.326, p = 0.011), and Triacylglycerol 52:6 (OR: 1.161, 95% CI: 1.007–1.339, p = 0.040) exhibited a positive correlation with an elevated risk of BC. Conclusion Genetic projections suggest a reciprocal causal link between the lipidome and BC, offering theoretical support and a basis for future clinical research.

De novo renal transplant carcinoma, especially in the context of bilateral renal carcinoma, is rare and often presents as small, low-grade papillary renal cell carcinoma (RCC). There is currently no consensus or effective treatment for advanced metastatic RCC after kidney transplantation. A 40-year-old man developed de novo renal transplant carcinoma with venous thrombus and lung metastases 20 years after transplantation. The patient underwent cytoreductive nephrectomy followed by sequential treatment with tyrosine kinase inhibitors (TKI) and anti-PD-1 monoclonal antibodies. After 2 years, the patient showed excellent graft function with no evidence of cancer progression. Despite subsequent graft failure, the disease remained controlled for more than 2 years and the patient survived for more than 3 years, which was significantly longer than the typical survival of 10 to 20 months in patients with advanced kidney cancer. The results suggest that combining cytoreductive nephrectomy with TKI and anti-PD-1 therapy may significantly prolong survival in patients with renal allograft carcinoma.

Background: Reactive Oxygen Species (ROS), a hallmark of cancer, is related to prognosis, tumor progression, and treatment response. Nevertheless, the correlation of ROS-based molecular signature with clinical outcome and immune cell infiltration has not been thoroughly studied in bladder cancer (BLCA). Accordingly, we aimed to thoroughly examine the role and prognostic value of ROS-related genes in BLCA.Methods: We obtained RNA sequencing and clinical data from The Cancer Genome Atlas (TCGA) for bladder cancer (BLCA) patients and identified ROS-associated genes using the GeneCards and Molecular Signatures Database (MSigDB). We then analyzed differential gene expression between BLCA and normal tissues and explored the functions of these ROS-related genes through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analysis. Prognostic ROS-related genes were identified using Univariate Cox regression (UCR) and LASSO analyses, which were further refined in a Multivariate Cox Regression (MCR) analysis to develop a Prognostic Signature (PS). This PS was validated in the GSE13507 cohort, assessing its predictive power with Kaplan-Meier survival and time-dependent ROC curves. To forecast BLCA outcomes, we constructed a nomogram integrating the PS with clinical variables. We also investigated the signature’s molecular characteristics through Gene Set Enrichment Analysis (GSEA), Immune Cell Infiltration (ICI), and Tumor Mutational Burden (TMB) analyses. The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to predict chemotherapy responses based on the PS. Additionally, we screened for Small-Molecule Drugs (SMDs) targeting ROS-related genes using the CMAP database. Finally, we validated our findings by checking protein levels of the signature genes in the Human Protein Atlas (HPA) and confirmed the role of Aldo–keto reductase family 1 member B1 (AKR1B1) through in vitro experiments.Results: The constructed and validated PS that comprised 17 ROS-related genes exhibited good performance in predicting overall survival (OS), constituting an independent prognostic biomarker in BLCA patients. Additionally, we successfully established a nomogram with superior predictive capacity, as indicated by the calibration plots. The bioinformatics analysis findings showcased the implication of PS in several oncogenic pathways besides tumor ICI regulation. The PS was negatively associated with the TMB. The high-risk group patients had greater chemotherapy sensitivity in comparison to low-risk group patients. Further, 11 candidate SMDs were identified for treating BLCA. The majority of gene expression exhibited a correlation with the protein expression. In addition, the expression of most genes was consistent with protein expression. Furthermore, to test the gene reliability we constructed, AKR1B1, one of the seventeen genes identified, was used for in-depth validation. In vitro experiments indicate that siRNA-mediated AKR1B1 silencing impeded BLCA cell viability, migration, and proliferation.Conclusions: We identified a PS based on 17 ROS-related genes that represented independent OS prognostic factors and 11 candidate SMDs for BLCA treatment, which may contribute to the development of effective individualized therapies for BLCA.

Bladder cancer (BC) is a prevalent type of tumor in the urinary system, and it has been discovered that long non‐coding RNA (lncRNA) plays a significant role in its occurrence and development. However, thus far, no reports have been published on the involvement of LINC00461 in BC. Here, we found that LINC00461 levels were upregulated in BC tissues and cell lines. Besides, knockdown of LINC00461 inhibited BC cell proliferation, migration, invasion through epithelial-mesenchymal transition (EMT), and slowed down tumor growth in vivo. Moreover, we found that LINC00461 regulated HNRNPUL1 expression through miR-518b sponge activity, and the miR-518 inhibitor could reverse the inhibitory effects of LINC00461 knockdown on BC cell proliferation, migration, and EMT. Our results suggest that LINC00461 may serve as a potential biomarker and therapeutic target for BC.

Increasing evidence has confirmed the vital role of Notch signaling in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). The underlying function of long non-coding RNA (lncRNA) related to Notch signaling in ccRCC remains unclear. In present study, the prognostic value and therapeutic strategy of Notch signaling-related lncRNA are comprehensively explored in ccRCC. In total, we acquired 1422 NSRlncRNAs, of which 41 lncRNAs were identified the key NSRlncRNAs associated with the occurrence of ccRCC. The prognostic signature containing five NSRlncRNAs (AC092611.2, NNT-AS1, AGAP2-AS1, AC147651.3, and AC007406.3) was established and validated, and the ccRCC patients were clustered into the high- and low-risk groups. The overall survival of patients in the low-risk group were much more favorable than those in the high-risk group. Multivariate Cox regression analysis indicated that the risk score was an independent prognostic biomarker. Based on the risk score and clinical variables, a nomogram for predicting prognosis of ccRCC patients was constructed, and the calibration curves and DCA curves showed the superior predictive ability of nomogram. The risk score was correlated with immune cell infiltration, targeted therapy or chemotherapy sensitivity, and multiple oncogenic pathways. Additionally, consensus clustering analysis stratified the ccRCC patients into four clusters with obvious different outcomes, immune microenvironments, and expression of immune checkpoints. The constructed NSRlncRNA-based signature might serve as a potential biomarker for predicting prognosis and response to immunotherapy or targeted therapy in patients with ccRCC.

Immune checkpoint inhibitors (ICIs) have been approved as an emerging first-line treatment option for advanced and metastatic urothelial carcinoma whose tumors express programmed death-ligand 1 (PD-L1). However, the efficacy of immunotherapy in PD-L1-negative urothelial carcinoma patients remains unclear, and biomarkers beyond PD-L1 expression to predict response to immunotherapy need investigation. Here, we report a metastatic renal pelvis urothelial carcinoma patient with PD-L1 negative expression that responded dramatically to first-line pembrolizumab plus lenvatinib. By the recent follow-up in March 2022, the patient had a complete radiological response for 3.4 years, with no recurrence even during the 23-month drug-withdrawal period. The results of the next-generation sequencing using the tumor sample revealed a high tumor mutational burden (TMB), which may be independently driven by the pathogenic mutation in TP53, TERT, NCOR1, and TSC2 genes. Besides, the tumor microenvironment exhibited an immune-active signature with relatively abundant CD8+ cells and M1 tumor-associated macrophages but scarce regulatory T cells may also explain the great benefit of the combination therapy. Our case provides a direction for identifying biomarkers beyond PD-L1 expression to screen urothelial carcinoma patients who benefit from ICI as well as ICI-based therapy.

Metastatic urothelial carcinoma (mUC) is associated with poor prognosis. Cisplatin-based combination chemotherapy is the preferred initial regimen for patients with mUC. However, a substantial proportion of patients cannot receive cisplatin-based chemotherapy due to renal impairment or other comorbidities. Currently, immune checkpoint inhibitors (ICI) showed to be effective in cisplatin-ineligible mUC patients on first-line treatment. Tislelizumab is an anti-human programmed death receptor-1 monoclonal IgG4 antibody, which was specifically engineered to minimize binding to FcɣR on macrophages to abrogate antibody-dependent phagocytosis. But there is no report of tislelizumab as a first-line treatment for cisplatin-ineligible patients with mUC currently. Here, we report a cisplatin-ineligible mUC patient with PD-L1-negative, microsatellite stable (MSS), high tumor mutational burden (TMB-H) obtained complete response receiving tislelizumab therapy after laparoscopic debulking surgery. Progression-free survival has exceeded 16 months since treatment with tislelizumab. To our knowledge, this is the first reported case of cisplatin-ineligible mUC patient with PD-L1-negative, MSS and TMB-H who responded well to tislelizumab as a first-line treatment. However, we still need more studies to assess the efficacy of tislelizumab as a first-line treatment in cisplatin-ineligible mUC patients and to confirm predictive values of TMB for efficacy of tislelizumab.