Discover. Oncology最新文献

Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with poor prognosis, partly due to an immunosuppressive tumor microenvironment. The immune-related gene CCDC86, selectively expressed in hematopoietic and antigen-presenting cells, has not been previously characterized in HNSCC. We aimed to delineate its expression pattern and immunological functions using integrated single-cell transcriptomic analysis.

Methods: Bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and single-cell RNA-sequencing data (GEO: GSE139324) were integrated to assess CCDC86 expression, immune-cell specificity, and associated transcriptional programs in HNSCC. Differential expression, pathway enrichment, transcription factor regulon, and cell-cell communication analyses were conducted between CCDC86-high and CCDC86-low populations. The immune contexture and ligand-receptor interactions of CCDC86-expressing cells were evaluated to infer their roles in tumor-immune modulation. Additionally, qPCR validation following CCDC86 knockdown in FaDu cells was performed to confirm the transcriptional alterations of immune-related genes identified by bioinformatic analysis.

Results: CCDC86 was predominantly expressed in tumor-infiltrating antigen-presenting cells (APCs), including macrophages and dendritic cells. CCDC86-high APCs exhibited enhanced SPI1- and CEBPA-regulated transcriptional activity, metabolic reprogramming, and altered antigen-presentation signatures.Ligand-receptor network analysis revealed intensified interactions with T cells via both co-stimulatory (CD86-CD28) and checkpoint (PDCD1, CTLA4) pathways, suggesting dual immunomodulatory potential. Functionally, CCDC86-high APCs were associated with increased cytotoxic T-cell infiltration but concurrent T-cell dysfunction, implying that CCDC86 defines a specialized APC state that sustains chronic immune activation yet promotes tolerance within the tumor microenvironment. Additionally, qPCR validation following CCDC86 knockdown in FaDu cells was performed to confirm the transcriptional alterations of immune-related genes identified by bioinformatic analysis.

Conclusions: CCDC86 acts as a key regulator of immune communication in HNSCC, orchestrating APC-T cell interactions and shaping an immunoregulatory niche. By linking antigen presentation with checkpoint signaling, CCDC86 contributes to immune evasion while maintaining local immune activation. These findings highlight CCDC86 as a promising prognostic biomarker and potential immunotherapeutic target in HNSCC.

Deubiquitination(DUB) is a critical cellular process that regulates protein stability and functionality, playing essential roles in cell proliferation, migration, tumorigenesis, and various molecular signaling pathways. Within the DUB enzyme family, ubiquitin-specific protease 33 (USP33) is found to be aberrantly expressed in several cancers, including a significant reduction in colorectal cancer (CRC) tissues. The decreased expression of USP33 impairs its ability to inhibit CRC cell proliferation, migration, and invasion, potentially through its involvement in key signaling pathways such as the β-arrestin-dependent ERK pathway, Slit-Robo pathway, and Wnt/β-catenin pathway. This review highlights the interaction between USP33 and these signaling pathways, exploring its potential as a novel independent prognostic biomarker for CRC and its promise as a therapeutic target.

Background: N-Nitrosodimethylamine (NDMA), classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC), is ubiquitous in drinking water, processed foods, and certain pharmaceuticals. Emerging epidemiological evidence links NDMA exposure to an increased risk of Bladder Urothelial Carcinoma (BLCA), yet the specific molecular mechanisms driving its role in BLCA initiation and progression remain unclear.

Objective: This study aimed to elucidate the mechanisms of NDMA-induced BLCA by identifying core targets, validating their expression and immune correlation, and constructing a hypothetical Adverse Outcome Pathway (AOP) framework for NDMA-associated BLCA.

Methods: We integrated network toxicology and machine learning (LASSO, SVM-RFE, Random Forest) to screen core targets from the intersection of NDMA-related and BLCA-related genes obtained from public databases. Their expression levels and diagnostic value were validated using GEO (GSE13507) and TCGA data. Immune infiltration analysis, molecular docking, and 100-ns molecular dynamics simulations were performed to assess tumor microenvironment associations and NDMA-target binding stability, followed by the establishment of an AOP framework.

Results: A total of 575 intersecting targets were identified, with five core targets (IL7R, BCL2, CDC20, GADD45A, NRAS) screened via machine learning. These targets exhibited significant dysregulation in BLCA samples (p < 0.01) and demonstrated strong diagnostic performance (AUC: 0.766-0.869). Furthermore, core targets showed distinct correlations with immune cell infiltration. Molecular docking confirmed stable binding of NDMA to all targets, with the highest affinity observed for BCL2, which was further validated by dynamics simulations. Based on these findings, a novel AOP framework was proposed: NDMA exposure → dysregulation of core targets → pathway disruption → immune microenvironment imbalance and epithelial cell dysfunction → BLCA progression.

Conclusion: NDMA likely promotes BLCA through multi-target and multi-pathway mechanisms. The identified core genes serve as potential diagnostic biomarkers, and the proposed AOP provides a theoretical basis for environmental risk assessment and targeted intervention strategies.

Background: AHNAK2 is acknowledged to function as an oncoprotein that enhances the invasive and metastatic potential of tumor cells in multiple types of malignancy. Nevertheless, its specific role in gastric cancer (GC) remains unclear.

Methods: Immunohistochemistry (IHC) was used to examine AHNAK2 expression in matched GC tissues and paracancerous tissues, Clinical and pathological data was gathered for the purpose of investigate the association of AHNAK2 expression and prognosis in patients with GC. AHNAK2 protein expression and location was examined using Western blotting (WB) and immunofluorescence (IF). The effects of AHNAK2 knockdown on the malignant biological behavior of GC cells were evaluated. Transcriptome sequencing and WB analyses were conducted to explore the potential molecular mechanisms underlying AHNAK2-mediated regulation of GC progression.

Results: WB, IF, and IHC analyses demonstrate that AHNAK2 expression is upregulated in GC, and patients with high AHNAK2 protein expression exhibit poorer overall survival rates. Knockdown of AHNAK2 results in reduced invasive, proliferative, and migratory capacities of GC cells, along with increased apoptosis. RNA sequencing and WB analysis further confirmed that AHNAK2 exacerbates the malignant phenotypic characteristics of GC through activation of the Wnt/β-catenin pathway.

Conclusion: AHNAK2 may serve as a new prognostic biomarker and a prospective therapeutic target in GC.