Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cancer. Cuproptosis is suggested to be a novel therapy target for cancer treatment. However, the function of cuproptosis and its key regulator FDX1 in ccRCC remains unclear. In this study, we adequately explored the prognostic factors, clinicopathological characteristics, and function of FDX1 in ccRCC. We found that the expression of FDX1 was significantly downregulated in ccRCC samples. Patients with a higher FDX1 expression had a significantly better prognosis, including overall survival (OS) (Hazard ratio (HR): 2.54, 95% confidence interval (CI): 1.82–3.53, p < 0.001), disease-specific survival (DSS) (HR: 3.04, 95% CI: 2.04–4.54, p < 0.001), and progression-free survival (PFS) (HR: 2.54, 95% CI: 1.82–3.53, p < 0.001). FDX1 was a clinical predictor to stratify patients into the high or low risk of poor survival, independent of conventional clinical features, with the area under the ROC curve (AUC) of 0.658, 0.677, and 0.656 for predicting the 5-year OS, DSS, and PFS. The nomogram model based on FDX1 had greater predictive power than other individual prognostic parameters. FDX1 mainly participated in the oxidative-related process and mitochondrial respiration-related processes but was not associated with immune infiltration levels. In conclusion, the cuproptosis key regulator FDX1 could serve as a potential novel prognostic biomarker for ccRCC patients.

Background: This study aimed to explore the relationship between diabetes risk reduction diet (DRRD) and bladder cancer risk in Prostate, Lung, Colorectal, Ovarian (PLCO) cohort. Methods: Data from 99,001 participants in the PLCO Cancer Screening Trial were analyzed using Cox proportional hazards regression models to estimate HRs and 95% confidence intervals (CI) for the association between DRRD score and bladder cancer incidence. Subgroup analyses were conducted to assess whether variables such as age, sex, body mass index, cigarette smoking status, and history of diabetes influenced the observed association. The DRRD score was formulated on the basis of nine nutrient intake indicators derived from the Dietary History Questionnaire. Results: During the median follow-up of 11.7 years, 761 new bladder cancer cases were identified. Participants with highest DRRD scores exhibited a reduced risk of bladder cancer compared with those in the lowest quartile (unadjusted analysis, HR, 0.65; 95% CI, 0.53–0.82); multivariable adjusted analysis, HR, 0.79; 95% CI, 0.64–0.98; Ptrend = 0.007). A similar risk reduction was seen solely in transitional cell carcinoma (HR, 0.79; 95% CI, 0.64–0.99; P = 0.007). In addition, the significant negative association between DRRD scores and bladder cancer risk persisted even after excluding participants with unique characteristics. Conclusions: This large prospective population-based study suggests that adherence to a DRRD may contribute to the prevention of bladder cancer. Impact: The DRRD could potentially mitigate bladder cancer risk, which warrants further validation in diverse populations.

This study aims to explore the role of abnormal fatty acid metabolism (FAM) in ccRCC and construct a novel fatty acid metabolism-related gene signature (FAMGS) for prognosis. Three independent ccRCC cohorts, including The Cancer Genome Atlas, E-MTAB-1980 and our clinical cohort (including RNA-seq, microarray and RT-qPCR data), were applied as training and two independent validation cohorts. Firstly, FAM levels were found to be significantly decreased in ccRCC and correlated with degrees of malignancy, confirming the pivotal role of FAM in ccRCC. Applying the least absolute shrinkage and selection operator cox regression, we established a novel FAMGS for overall survival (OS). The FAMGS divided patients into low or high-risk groups in the training cohort and were successfully validated in both the EMTAB and our clinical validation cohorts. Additionally, the FAMGS serves as an independent risk factor for OS of ccRCC. Results of the immune cell abundance identifier (ImmuCellAI) algorithm and gene set variation analysis (GSVA) revealed that patients in the high-risk group have comprehensively impaired metabolism, including lipids, amino acids and tricarboxylic acid cycle-related pathways and a more immunosuppressive tumor microenvironment. In conclusion, our study constructed and validated a novel FAMGS, which may improve the risk stratification optimization and personalized management of ccRCC.

This study explores the immune repertoire landscape of B cell receptor (BCR) in renal allografts with T cell‐mediated rejection (TCMR) to identify new therapeutic targets due to the limitations of current immunosuppressive treatments. BCR repertoires were constructed from both bulk and single‐cell RNA‐seq data utilizing the TRUST4 algorithm. The study revealed a significant expansion of the BCR repertoire, particularly Immunoglobulin G in TCMR compared to stable renal function across three independent renal transplant cohorts. By integrating multi‐omics data from various datasets including bulk transcriptomic data, single‐cell transcriptome profiles, cell line data, and immunofluorescence of renal allograft biopsies, the infiltrated plasma cell was identified as the primary holder of BCRs in renal allografts with TCMR, serving as an independent risk factor for prognosis. Additionally, MEI1 was discovered as a novel BCR‐related key gene in TCMR, upregulated during plasma cell maturation and contributing to antibody secretion. This study first delineated the BCR repertoire landscape in TCMR, highlighting the crucial role of BCR, allograft‐infiltrated plasma cells, and MEI1 in TCMR, thus offering novel therapeutic targets for improving allograft outcomes.

Background:This study aimed to explore the relationship between diabetes risk reduction diet (DRRD) and bladder cancer risk in Prostate, Lung, Colorectal, Ovarian (PLCO) cohort.Methods:Data from 99,001 participants in the PLCO Cancer Screening Trial were analyzed using Cox proportional hazards regression models to estimate HRs and 95% confidence intervals (CI) for the association between DRRD score and bladder cancer incidence. Subgroup analyses were conducted to assess whether variables such as age, sex, body mass index, cigarette smoking status, and history of diabetes influenced the observed association. The DRRD score was formulated on the basis of nine nutrient intake indicators derived from the Dietary History Questionnaire.Results:During the median follow-up of 11.7 years, 761 new bladder cancer cases were identified. Participants with highest DRRD scores exhibited a reduced risk of bladder cancer compared with those in the lowest quartile (unadjusted analysis, HR, 0.65; 95% CI, 0.53–0.82); multivariable adjusted analysis, HR, 0.79; 95% CI, 0.64–0.98; Ptrend = 0.007). A similar risk reduction was seen solely in transitional cell carcinoma (HR, 0.79; 95% CI, 0.64–0.99; P = 0.007). In addition, the significant negative association between DRRD scores and bladder cancer risk persisted even after excluding participants with unique characteristics.Conclusions:This large prospective population-based study suggests that adherence to a DRRD may contribute to the prevention of bladder cancer.Impact:The DRRD could potentially mitigate bladder cancer risk, which warrants further validation in diverse populations.