Zhijie Wang

Integrative Analysis of Novel Ferroptosis‐Related Genes Signatures as Prognostic Biomarkers in Ovarian Cancer

ABSTRACTBackgroundFerroptosis, an iron‐dependent form of cell death, has been implicated in the pathogenesis of several types of cancer. Nevertheless, the exact correlation between ferroptosis‐related gene mutations and their influence on ovarian cancer (OV) diagnosis and treatment strategies remains to be fully elucidated. It is crucial to identify the ferroptosis‐related gene signature in OV and elucidate the impact of these mutations and their expression on the diagnosis and treatment of OV.MethodsIn this study, we collected data from the TCGA and GEO databases. We utilized various tools and packages for data analysis, including the cBio Cancer Genomics Portal, Tumor Immune Estimation Resource (TIMER), GSVA package, and WGCNA R packages.ResultsOur results showed that ferroptosis subtypes 1 (FS1) and 2 (FS2) exhibited different levels of expression and tumor mutation burden (TMB). FS2 had a higher TMB level and survival rate compared to FS1. Furthermore, our analysis identified three ferroptosis‐related genes, including IFNG, KEAP1, and PHKG2, as key biomarkers in prognosis prediction and potential targets for OV cancer therapy. The elevated expression levels of IFNG, KEAP1, and PHKG2 were found to be correlated with a good prognosis. These three genes showed a positive correlation with TMB in OV. We also observed that high TMB was more robustly associated with immune response‐related gene expression, including CD28, CD40L, and type I IFN family members. Moreover, high TMB was associated with increased T cell infiltration and exhibited a distinct gene signature, which highlights the potential of IFNG, KEAP1, and PHKG2 as predictive markers for T cell infiltration and the tumor microenvironment status in OV. A significant correlation exists between the expression levels of KEAP1 and PHKG2 and TMB in OV cell lines.ConclusionIn conclusion, our study identified KEAP1, IFNG, and PHKG2 as potential prognostic biomarkers and therapeutic targets in OV. Their expression and mutation burden were correlated with a good prognosis. The association between ferroptosis subtypes, TMB, and survival rates further supports the relevance of these biomarkers. Additionally, the positive correlation between KEAP1, IFNG, and PHKG2 with TMB and immune response‐related gene expression highlights their potential as predictive markers for immunotherapy efficacy in OV. The observed association of high TMB with increased T cell infiltration and distinct gene signature further emphasizes its role as a potential biomarker for immune response. Further research is warranted to validate these findings and explore their clinical implications in OV treatment.

Development and clinical validation of an ERA-CRISPR/Cas12a assay for the rapid detection of 14 high-risk HPV types

ABSTRACT Persistent infection with high-risk human papillomavirus (HR-HPV) is the leading cause of cervical cancer, highlighting the critical need for early detection to improve prevention. Although real-time quantitative polymerase chain reaction (RT-qPCR) remains the gold standard for HR-HPV detection, its dependence on sophisticated equipment, complex procedures, and trained personnel limits accessibility. Here, we developed a simplified assay for 14 HR-HPV types by integrating direct lysis, enzyme-mediated isothermal rapid amplification (ERA), and CRISPR-Cas12a-mediated cleavage into a streamlined workflow that requires only a basic isothermal heating device. The optimized system achieved a sensitivity of 50 copies per reaction with no cross-reactivity, while a refined lysis buffer containing 20% Chelex-100 minimized inhibition from vaginal swab samples, thereby enhancing detection performance. Validation with 152 clinical samples demonstrated 97.62% sensitivity and 100% specificity, confirming the reliability of the method. This user-friendly and cost-effective assay requires minimal equipment, enabling rapid and field-deployable HR-HPV detection, and offers a practical alternative to conventional laboratory-based approaches, particularly in resource-limited settings. IMPORTANCE High-risk human papillomavirus (HR-HPV) is the principal etiological agent of cervical cancer, and early detection remains central to effective disease prevention. Current PCR-based assays, however, rely on specialized laboratories and trained personnel, limiting their deployment in many settings. Here, we report a streamlined CRISPR-Cas12a assay that integrates direct sample lysis, ERA, and CRISPR-based detection into a single workflow operable with only a simple heating device to determine the presence of 14 HR-HPV types. The assay achieves high analytical sensitivity, strong specificity, and robust clinical performance while maintaining low cost and ease of use. This platform enables rapid HR-HPV detection and scalable screening, particularly in resource-constrained environments, with the potential to facilitate earlier intervention and reduce cervical cancer incidence.

Efficacy and safety of VEGFR inhibitors for recurrent ovarian cancer: a systematic review