Background: Head and neck squamous cell carcinoma (HNSCC), the most common head and neck cancer, is highly aggressive and heterogeneous, resulting in variable prognoses and immunotherapeutic outcomes. Natural killer (NK) cells play essential roles in malignancies’ development, diagnosis, and prognosis. The purpose of this study was to establish a reliable signature based on genes related to NK cells (NRGs), thus providing a new perspective for assessing immunotherapy response and prognosis of HNSCC patients.Methods: In this study, NRGs were used to classify HNSCC from the TCGA-HNSCC and GEO cohorts. The genes were evaluated using univariate cox regression analysis based on the differential analysis of normal and tumor samples in TCGA-HNSCC conducted using the “limma” R package. Thereafter, we built prognostic gene signatures using LASSO-COX analysis. External validation was carried out in the GSE41613 cohort. Immunity analysis based on NRGs was performed via several methods, such as CIBERSORT, and immunotherapy response was evaluated by TIP portal website.Results: With the TCGA-HNSCC data, we established a nomogram based on the 17-NRGs signature and a variety of clinicopathological characteristics. The low-risk group exhibited a better effect when it came to immunotherapy.Conclusions: 17-NRGs signature and nomograms demonstrate excellent predictive performance and offer new perspectives for assessing pre-immune efficacy, which will facilitate future precision immuno-oncology research.
Background: Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with a poor prognosis for advanced tumors. Anoikis play a key role in cancer metastasis, facilitating the detachment and survival of cancer cells from the primary tumor site. However, few studies have focused on the role of anoikis in HNSC, especially on the prognosis.Methods: Anoikis-related genes (ANRGs) integrated from Genecards and Harmonizome portals were used to identify HNSCC subtypes and to construct a prognostic model for HNSCC patients. Also, we explored the immune microenvironment and enrichment pathways between different subtypes. Finally, we provide clinical experts with a novel nomogram based on ANRGs, with DCA curves indicating the potential clinical benefit of the model for clinical strategies.Results: We identified 69 survival-related HNSCC anoikis-related DEGs, from which 7 genes were selected to construct prognostic models. The prognostic risk score was identified as an independent prognostic factor. Functional analysis showed that these high and low risk groups had different immune status and drug sensitivity. Next risk scores were combined with HNSCC clinicopathological features together to construct a nomogram, and DCA analysis showed that the model could benefit patients from clinical treatment strategies.Conclusion: The predictive seven-gene signature and nomogram established in this study can assist clinicians in selecting personalized treatment for patients with HNSCC.
Alzheimer’s disease (AD) is a serious brain disorder characterized by the presence of beta-amyloid plaques, tau pathology, inflammation, neurodegeneration, and cerebrovascular dysfunction. The presence of chronic neuroinflammation, breaches in the blood-brain barrier (BBB), and increased levels of inflammatory mediators are central to the pathogenesis of AD. These factors promote the penetration of immune cells into the brain, potentially exacerbating clinical symptoms and neuronal death in AD patients. While microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in AD, recent evidence suggests the infiltration of cerebral vessels and parenchyma by peripheral immune cells, including neutrophils, T lymphocytes, B lymphocytes, NK cells, and monocytes in AD. These cells participate in the regulation of immunity and inflammation, which is expected to play a huge role in future immunotherapy. Given the crucial role of peripheral immune cells in AD, this article seeks to offer a comprehensive overview of their contributions to neuroinflammation in the disease. Understanding the role of these cells in the neuroinflammatory response is vital for developing new diagnostic markers and therapeutic targets to enhance the diagnosis and treatment of AD patients.
The progression of differentiated thyroid carcinoma (DTC) poses significant clinical challenges, especially in determining the optimal time for intervention. To capture early signals of disease progression, we employed an optimized dynamic network biomarker (DNB) method—a systems biology approach that detects abrupt molecular changes indicating a critical transition signal. This analysis revealed that Stage II marks a critical transition in the disease trajectory. We further developed a scoring system called TCPSLevel (Thyroid Carcinoma Progression Signature Level), which quantifies individual progression risk based on gene expression profiles. TCPSLevel showed strong associations with clinical features and prognosis across multiple datasets. Our ensemble consensus clustering approach uncovered three robust DTC molecular subtypes, which demonstrated distinct clinical outcomes, immune microenvironments, regulatory landscapes, and therapeutic agents. A clinically applicable classifier (miniPC) was constructed using machine learning to facilitate subtype prediction. We also identified ASPH as a key regulator driving progression and validated its expression and function experimentally. Together, these findings offer new insights and practical tools for early risk assessment and personalized management of thyroid cancer.
HBV infection profoundly escalates hepatocellular carcinoma (HCC) susceptibility, responsible for a majority of HCC cases. HBV-driven immune-mediated hepatocyte impairment significantly fuels HCC progression. Regrettably, inconspicuous early HCC symptoms often culminate in belated diagnoses. Nevertheless, surgically treated early-stage HCC patients relish augmented five-year survival rates. In contrast, advanced HCC exhibits feeble responses to conventional interventions like radiotherapy, chemotherapy, and surgery, leading to diminished survival rates. This investigation endeavors to unearth diagnostic hallmark genes for HBV-HCC leveraging a bioinformatics framework, thus refining early HBV-HCC detection. Candidate genes were sieved via differential analysis and Weighted Gene Co-Expression Network Analysis (WGCNA). Employing three distinct machine learning algorithms unearthed three feature genes (HHIP, CXCL14, and CDHR2). Melding these genes yielded an innovative Artificial Neural Network (ANN) diagnostic blueprint, portending to alleviate patient encumbrance and elevate life quality. Immunoassay scrutiny unveiled accentuated immune damage in HBV-HCC patients relative to solitary HCC. Through consensus clustering, HBV-HCC was stratified into two subtypes (C1 and C2), the latter potentially indicating milder immune impairment. The diagnostic model grounded in these feature genes showcased robust and transferrable prognostic potentialities, introducing a novel outlook for early HBV-HCC diagnosis. This exhaustive immunological odyssey stands poised to expedite immunotherapeutic curatives' emergence for HBV-HCC.
Thymic epithelial tumors (TETs) are a rare and diverse group of neoplasms characterized by distinct molecular signatures. This review delves into the complex molecular networks of TETs, highlighting key aspects such as chromosomal abnormalities, molecular subtypes, aberrant gene mutations and expressions, structural gene rearrangements, and epigenetic changes. Additionally, the influence of the dynamic tumor microenvironment on TET behavior and therapeutic responses is examined. A thorough understanding of these facets elucidates TET pathogenesis, offering avenues for enhancing diagnostic accuracy, refining prognostic assessments, and tailoring targeted therapeutic strategies. Our review underscores the importance of deciphering TETs’ unique molecular signatures to advance personalized treatment paradigms and improve patient outcomes. We also discuss future research directions and anticipated challenges in this intriguing field.