TOP2A (DNA topoisomerase 2-alpha)

As the signature relies exclusively on IHC, it is simple, cost-effective and readily integratable into routine diagnostic workflows. In addition to its prognostic value, several biomarkers within the panel are potentially actionable, offering opportunities to guide targeted therapies in patients predicted to have poor response to conventional chemotherapy.

Future directions emphasize integrating antigen discovery with immune profiling, refining preclinical modeling, and developing personalized vaccines to enhance therapeutic efficacy, particularly for immunologically favorable patient subtypes and for certain applications such as reducing metastasis after surgery. In particular, we discuss carrier-based vaccine approaches for overcoming tolerance and increasing the immunogenicity of vaccines.

Overall, our study indicates that the molecular mechanisms underlying disturbed PNP in IPMNs are not mediated by a single pathway but involve multiple interconnected pathways. Our findings may contribute to elucidation of the molecular mechanisms regulating PNP in IPMNs, enhancing our understanding of tumor progression and contributing to more accurate pathological diagnosis.

Subgroup analysis revealed a distinct transcriptomic profile in leiomyosarcoma, while gene fusion analysis detected clinically relevant alterations. These findings demonstrate that RNA-NGS provides biologically and clinically meaningful insights into the molecular landscape of soft tissue sarcomas and supports its integration into precision medicine-oriented diagnostic workflows.

Remarkably, key K17-dependent readouts are rescued by expression of constitutively-active, but not dominant-negative, Rac mutants in KRT17 null A431 keratinocytes. These findings uncover a K17-Rac1-TOP2A signaling axis that promotes DNA damage response and associated proliferation, with implications for cancer and chronic skin diseases.

TOP2A, PABPN1, BCL2L12, TRIM14, PIK3R1 and LAPTM4B were novel PCD-related prognostic markers for PRAD. BCL2L12 might take part in the resistance of 6-AA in PRAD via the cysteine-type endopeptidase activity pathway.

TOP2A and PPARGC1A effectively stratify PCa subtypes for RAP patients. TOP2A drives malignant progression via the PI3K/AKT pathway.

Among four prioritized compounds, Ponatinib demonstrated the most favorable binding free energy, while Pimavanserin exhibited stable conformational behavior during simulation. These findings provide an in-silico prioritization framework for potential KIF11-targeting compounds in GBM. Experimental validation in relevant cellular and in vivo models will be required to determine biological and therapeutic relevance.

Our gene expression-based machine learning model provides a robust tool for HCC diagnosis, prognosis, and treatment response prediction, with potential as a supportive system for personalized clinical decision-making.

To summarize, these findings demonstrate that Ten effectively inhibits lung cancer and activates immunocytes by KDM5B inhibition, which is regulated by TEX264-associated ER-phagy. Most importantly, OTUD3 serves as an essential target for enhancement of TEX264 stabilization.

This integrative, severity-stratified analysis identifies shared molecular and regulatory features linking severe COVID-19 with aggressive cancers, highlighting persistent immune activation and altered immune communication as common underlying themes without implying causality or clinical outcome effects. These findings provide a systems-level, hypothesis-generating framework for understanding virus-cancer interactions and may inform future biomarker discovery and immune-focused therapeutic strategies in vulnerable cancer populations.