Ferroptosis and disulfidptosis are regulatory forms of cell death that play an important role in tumorigenesis and progression. However, few biomarkers about disulfidptosis and ferroptosis related genes (DFRGs) have been developed to predict the prognosis of bladder cancer (BC). We conducted a bioinformatics analysis using public BC datasets to examine the prognostic significance of differentially expressed DFRGs. A Lasso regression was employed to create a prognostic prediction model from these DFRGs. Hub DFRGs that play a role in immunotherapy response and immunoregulation were pinpointed. Immunohistochemistry (IHC) experiment was performed to assess NUBPL and c-MYC expression in BC patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy at Peking University Cancer Hospital. We constructed a valid model to predict the prognosis of BC based on DFRGs and performed relevant validation, the results demonstrated that the model was an independent prognostic factor for BC. Further analysis indicated that the model score, combined with the expression of various immune factors and tumor mutation burden (TMB), could predict the prognosis for BC. In addition, we also found that NUBPL was strongly associated with prognosis and response to ICI treatment, and NUBPL may influence BC malignant progression through the c-MYC pathway. Our research findings highlight the satisfactory predictive value of DFRGs in the immune microenvironment and suggest that NUBPL may be a highly promising biomarker for predicting the prognosis and efficacy of ICI treatment in BC patients.
18 March 2025 in International Journal of Biological Macromolecules
CD70, a member of the tumor necrosis factor family, has been implicated in various cellular processes associated with tumorigenesis. Despite its known expression in certain cancers, a detailed pan-cancer analysis and functional validation in clear cell renal cell carcinoma (ccRCC) have not been comprehensively explored. We conducted a pan-cancer analysis using publicly available databases to investigate the expression and prognostic significance of CD70 across various cancer types. For functional validation, immunohistochemistry was performed on ccRCC and adjacent normal tissues to evaluate CD70 expression levels. Additionally, ccRCC organoid model was developed and subjected to CAR-T cell cytotoxicity assays to evaluate the efficacy of targeting CD70 in vitro. The pan-cancer analysis revealed elevated expression of CD70 in several cancer types, including ccRCC, where it correlated with poor prognosis. Immunohistochemical analysis confirmed significant overexpression of CD70 in ccRCC tissues compared to normal tissues. In the ccRCC organoid model, CAR-T cells targeting CD70 demonstrated effective cytotoxicity against organoids expressing CD70. The overexpression of CD70 across diverse cancer types underscores its potential as a universal biomarker. Importantly, our findings underscore the clinical relevance of CD70 as a critical oncogenic factor and a promising therapeutic target in ccRCC, with implications for advancing personalized medicine.
Background: Basement membrane (BM) is an important component of the extracellular matrix, which plays an important role in the growth and metastasis of tumor cells. However, few biomarkers based on BM have been developed for prognostic assessment and prediction of immunotherapy in bladder cancer (BLCA). Methods: In this study, we used the BLCA public database to explore the relationship between BM-related genes (BMRGs) and prognosis. A novel molecular typing of BLCA was performed using consensus clustering. LASSO regression was used to construct a signature based on BMRGs, and its relationship with prognosis was explored using survival analysis. The pivotal BMRGs were further analyzed to assess its clinical characteristics and immune landscape. Finally, immunohistochemistry was used to detect the expression of the hub gene in BLCA patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy in our hospital. Results: We comprehensively analyzed the relationship between BMRGs and BLCA, and established a prognostic-related signature which was an independent influence on the prognostic prediction of BLCA. We further screened and validated the pivotal gene-MMP14 in public database. In addition, we found that MMP14 expression in muscle invasive bladder cancer (MIBC) was significantly higher and high MMP14 expression had a poorer response to ICI treatment in our cohort. Conclusions: Our findings highlighted the satisfactory value of BMRGs and suggested that MMP14 may be a potential biomarker in predicting prognosis and response to immunotherapy in BLCA.
Large-scale sequencing plays important roles in revealing the genomic map of ccRCC and predicting prognosis and therapeutic response to targeted drugs. However, the relevant clinical data is still sparse in Chinese population. Fresh tumor specimens were collected from 66 Chinese ccRCC patients, then the genomic RNAs were subjected to whole transcriptome sequencing (WTS). We comprehensively analyzed the frequently mutated genes from our hospital’s cohort as well as TCGA-KIRC cohort. VHL gene is the most frequently mutated gene in ccRCC. In our cohort, BAP1 and PTEN are significantly associated with a higher tumor grade and DNM2 is significantly associated with a lower tumor grade. The mutant type (MT) groups of BAP1 or PTEN, BAP1 or SETD2, BAP1 or TP53, BAP1 or MTOR, BAP1 or FAT1 and BAP1 or AR had a significantly correlation with higher tumor grade in our cohort. Moreover, we identified HMCN1 was a hub mutant gene which was closely related to worse prognosis and may enhance anti-tumor immune responses. In this preliminary research, we comprehensively analyzed the frequently mutated genes in the Chinese population and TCGA database, which may bring new insights to the diagnosis and medical treatment of ccRCC.
Background: Prostate cancer is among the most prevalent malignancies worldwide, and cardiovascular disease (CVD) is a major non‐cancer cause of death in affected patients. Androgen deprivation therapy (ADT), a mainstay treatment, has raised concerns about cardiotoxicity, yet the CVD risks of individual ADT agents remain unclear. Objectives: To assess cardiovascular adverse events (AEs) associated with specific ADT drugs using data from the U.S. FDA Adverse Event Reporting System (FAERS). Methods: AE reports related to ADT drugs were extracted from FAERS (Q1 2004–Q3 2024). Disproportionality analyses—including Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR)—were conducted to identify significant cardiovascular safety signals. Results: Different ADT agents exhibited distinct cardiovascular AE profiles. Some drugs were linked to a broader range of CVD‐related AEs, while others had more limited associations. Conclusions: ADT agents demonstrate heterogeneous cardiotoxicity profiles. These findings emphasize the need for individualized treatment strategies, particularly in patients with pre‐existing CVD risks, and may aid clinicians in balancing cancer control with cardiovascular safety.