Head and neck cancers (HNCs) are common malignancies with generally unfavorable prognoses worldwide, among which squamous cell carcinoma (SCC) represents the predominant histological type. The Combined Positive Score (CPS), a key metric for evaluating PD-L1 expression, has demonstrated predictive value for response to immunotherapy across various solid tumors. However, its distribution patterns and clinical significance among tumors originating from different anatomical subsites within the head and neck region remain unclear.This retrospective study included 591 patients with malignant head and neck tumors treated at Beijing Tongren Hospital between January 2022 and November 2024, comprising 316 hypopharyngeal, 202 laryngeal, 45 oropharyngeal, and 28 nasal cavity and paranasal sinus carcinoma. PD-L1 expression was assessed using the PD-L1 IHC 22C3 pharmDx assay, and CPS was calculated accordingly. Results showed that the CPS was significantly lower in hypopharyngeal carcinoma (18.89 ± 21.65) compared to oropharyngeal carcinoma (24.71 ± 25.97; P < 0.05). Furthermore, CPS was negatively correlated with tumor differentiation in hypopharyngeal cancer (r = -0.1434, P = 0.018), with a similar trend observed in laryngeal cancer (P = 0.054), whereas no significant correlation was found in oropharyngeal or nasal cavity and paranasal sinus carcinoma.Survival analysis in the immunotherapy-treated subgroup revealed no statistically significant differences in overall survival (OS) or progression-free survival (PFS) between patients with CPS ≥ 20 and those with CPS < 20. However, in hypopharyngeal cancer, the CPS < 20 group exhibited a hazard ratio (HR) for death of 4.55 (95

Background Aerobic glycolysis drives cancer progression through phosphofructokinase (PFK)-mediated regulation. The contribution of platelet-type PFK (PFKP) to head and neck squamous cell carcinoma (HNSCC) pathogenesis remains undefined.Methods Bioinformatic screening of 548 TCGA-HNSCC cases identified glycolysis-related prognostic genes via Cox regression, followed by experimental validation using quantitative polymerase chain reaction (qPCR) and Kaplan-Meier survival analysis in 51 clinical HNSCC tissue pairs in our center. In vitro functional assays (CCK8, colony formation, migration assays and metabolic analysis experiments), co-immunoprecipitation, ubiquitination analysis, and immunofluorescence were performed in HNSCC cell lines. PFKP-AMOTL1 interaction was validated by protein-binding studies. In vivo tumor growth was assessed using nude mice models. Clinical correlation analysis utilized HNSCC patient cohorts. Statistical significance was determined by Student's t-test and ANOVA.Results PFKP emerged as the pivotal prognostic biomarker for HNSCC, demonstrating significant upregulation at mRNA/protein levels in tumors versus normal tissues (TCGA/clinical cohorts) and correlating with reduced overall and disease-specific survival. In vitro, PFKP overexpression enhanced aerobic glycolysis and epithelial-mesenchymal transition (EMT) in HNSCC cells. Mechanistically, PFKP directly bound AMOTL1, inhibiting its ubiquitin-mediated degradation. PFKP-driven glycolysis and EMT were AMOTL1-dependent. Furthermore, PFKP promoted YAP nuclear translocation via AMOTL1, suppressing Hippo pathway activity and amplifying glycolytic flux. In vivo, elevated PFKP accelerated tumor progression and glycolytic metabolism through AMOTL1/YAP/Hippo signaling.Conclusions PFKP remodels tumor metabolism and drives EMT in HNSCC via the AMOTL1/YAP/Hippo axis, highlighting its mechanistic and prognostic significance, and suggesting its potential as a future therapeutic target.

Oncolytic virotherapy (OVT) serves as a powerful platform for targeted prodrug delivery. Vaccinia virus (VACV) serves as an attractive oncolytic vector due to its favorable safety profile, ease of genetic modification, and inherent tumor selectivity. We engineered an oncolytic vaccinia virus, dTF-FCU1, by inserting the prodrug-converting enzyme gene FCU1 and deleting the J2R and F4L genes to enhance tumor selectivity. When combined with the prodrug 5-Fluorocytosine, dTF‑FCU1 induced pronounced DNA damage and immunogenic cell death in cancer cells. In murine cancer model, this combination significantly suppressed tumor growth, enhanced antitumor immunity by promoting cytotoxic CD8⁺ T‑cell infiltration, and alleviating immune resistance by reducing Tregs, exhausted T cells and M2-type macrophages, thus reshaping the tumor immune microenvironment. Our study demonstrates strong selectivity and high efficacy of the dTF-FCU1/5-FC strategy, supporting its further development into a cancer treatment.

BACKGROUND:Robust outcome data for anterior skull base cutaneous squamous cell carcinoma (cSCC) are limited, particularly as emerging therapies reshape management. We evaluated survival and prognostic factors following craniofacial resection. METHODS:Retrospective multi-institutional case-series (1995-2015) of patients who underwent skull base surgery for anterior face/scalp cSCC. Kaplan-Meier and Cox regression analyses assessed disease-free (DFS), disease-specific (DSS), and overall survival (OS). RESULTS:Among 112 patients, most had T4 (86.6%) and recurrent (71.4%) disease. Clear margins were achieved in 32.1%; 40.2% were involved. Five-year DFS, DSS, and OS were 46.9%, 68.4%, and 52.3%, respectively. Intracranial extension independently predicted worse OS (HR:6.54 [95% CI:2.61,16.38]) and DSS (HR:12.39 [95% CI:2.72,56.45]). Involved margins predicted recurrence on univariable analysis. Adjuvant therapy, predominantly post-operative radiotherapy, improved OS (HR: 0.54 [95% CI: 0.30,0.97]). Complications occurred in 38.4%, with 4.5% perioperative mortality. CONCLUSION:Advanced anterior skull base cSCC carries substantial morbidity and modest survival. These data provide a benchmark against which immunotherapy-based strategies should be evaluated.

Introduction: This study aimed to compare survival, response, and laryngeal function outcomes among three neoadjuvant regimens in patients with resectable locally advanced hypopharyngeal carcinoma (LAHC). Methods: In this multicenter, retrospective cohort study, 517 patients with untreated, resectable LAHC (T3‑4/N+/M0) received neoadjuvant therapy with taxane-platinum-fluorouracil (TPF), TPF plus targeted therapy, or taxane-platinum (TP) plus immunotherapy, followed by surgery-based multimodal therapy or radical (chemo)radiotherapy. Primary endpoints were overall survival (OS), progression-free survival (PFS), and laryngectomy-free survival (LFS). Results: Among 517 patients (median age 59 years, 98.1% male), 5‑year OS, PFS, and LFS rates were 42.7%, 39.1%, and 44.4%, respectively. The TP plus immunotherapy group demonstrated superior OS (HR 0.62, 95% CI 0.51–0.75), PFS (HR 0.65, 0.54–0.79), and LFS (HR 0.59, 0.48–0.72) compared with TPF‑based groups (all P < .001), and achieved the highest pCR (25.4%) and LPR (83.7%). Subsequent surgery‑based multimodal therapy was associated with superior survival compared with non‑surgical approaches (OS: HR, 0.32; 95% CI, 0.22–0.46; P < .001). Lymph node metastasis (N+) was an independent negative predictor for both OS (HR, 2.00; 95% CI, 1.22–3.26; P = .01) and pCR (OR, 2.14; 95% CI, 1.17–3.90; P = .01). P16 negativity was independently associated with treatment resistance (OR, 3.20; 95% CI, 1.17–8.71; P = .02). Conclusions: In conclusion, neoadjuvant chemoimmunotherapy was associated with significantly improved survival and higher laryngeal preservation rates compared with traditional TPF‑based regimens in resectable LAHC, supporting further evaluation of immunotherapy‑containing induction strategies.

Abstract Purpose Head and neck squamous cell carcinoma (HNSCC) continues to be a deadly cancer with heterogeneous molecular characteristics and poor survival outcomes, particularly in HPV- patients. This study aimed to identify key overexpressed genes that drive HNSCC progression, evaluate their prognostic value, and explore associations with HPV status, promoter methylation, and changes in the immune microenvironment. Methods Using bioinformatics tools (UALCAN, HPA, TISIDB), we analyzed TCGA-HNSC data to evaluate gene expression, survival correlations, HPV subgroup differences, promoter methylation, and immune infiltration patterns. Statistical significance was defined as p < 0.05. Results Among the top 50 overexpressed genes in HNSCC, eight (LAMC2, CDKN2A, MFAP2, CTHRC1, CXCL13, FST, SPP1, PLAU) exhibited significant survival associations (p < 0.05). HPV- tumors demonstrated marked upregulation of LAMC2, CTHRC1, FST, SPP1, and PLAU, alongside downregulation of CDKN2A and CXCL13. Promoter hypomethylation in tumor tissues correlated with overexpression of LAMC2, CTHRC1, CXCL13, FST, SPP1, and PLAU, whereas CDKN2A showed hypermethylation. Immune infiltration analysis revealed strong correlations between these genes and immunosuppressive Tregs or cytotoxic T-cell depletion. Conclusion This study identifies eight prognostic biomarkers in HNSCC linked to HPV-driven heterogeneity. These genes could be potential targets for therapy in combination with immunotherapy and epigenetic regulators, helping to overcome tumor resistance in HNSCC with different HPV status.

Accumulating evidence indicates that N6-methyladenosine (m6A) modification of circular RNAs (circRNAs) plays a pivotal role in regulating cancer progression. However, in head and neck squamous cell carcinoma (HNSCC), the biological functions and underlying mechanisms of m6A modification in circRNAs remain insufficiently elucidated. In this study, we analyzed the association between the expression of IGF2BP3—an upstream m⁶A reader—and clinical outcomes of HNSCC patients, followed by investigating the interaction between IGF2BP3 and circHECTD2 as well as the effect of m⁶A modification on this interaction. Additionally, we explored the molecular mechanism by which IGF2BP3 and circHECTD2 regulate HNSCC progression, focusing on their roles in modulating microRNAs (miRNAs) and target mRNAs, and validated the functional impacts of the IGF2BP3/circHECTD2 axis on HNSCC cell proliferation, invasion, and metastasis. We found high expression of the m⁶A reader IGF2BP3 was significantly associated with poor clinical outcomes in HNSCC patients. Further experiments showed that IGF2BP3 directly bound to circHECTD2 and stabilized it, and m⁶A modification of circHECTD2 enhanced this binding and stabilization effect. Mechanistically, circHECTD2 functioned as a competing endogenous RNA (ceRNA) to sponge hsa-miR-4310 and hsa-miR-7157-5p, thereby preventing the miRNA-mediated degradation of SMAD2 mRNA. Ultimately, the IGF2BP3/circHECTD2/SMAD2 axis was shown to promote HNSCC cell proliferation, invasion, and metastasis. We delineate an m6A-dependent IGF2BP3/circHECTD2/SMAD2 regulatory axis that contributes to HNSCC malignancy. Elevated IGF2BP3 expression correlates with poor patient outcome and enhances circHECTD2 stability through m6A-facilitated binding; circHECTD2 in turn acts as a ceRNA to sequester hsa-miR-4310 and hsa-miR-7157-5p, thereby maintaining SMAD2 expression. Functionally, this axis promotes HNSCC cell proliferation, invasion and metastasis. Collectively, these findings suggest that IGF2BP3 and circHECTD2 may serve as promising prognostic biomarkers and therapeutic targets for HNSCC.

Background Venous insufficiency is a major cause of flap failure in head and neck reconstruction. AI provides a reliable, convenient solution for early detection.Methods Clinical data and postoperative flap photos of head and neck cancer patients (2018-2024) at our center were retrospectively collected, categorized into normal and venous-insufficient groups. Eight machine learning classifiers and three deep learning models (ResNet, GoogleNet, Densenet) were built. SHAP and Grad-CAM visualization were used for feature analysis and validation.Results A total of 2575 flap images from 576 patients (2010 normal, 565 venous-insufficient) were analyzed. Random Forest performed best in machine learning (accuracy 90.25%, AUC 0.759), with SHAP identifying Hue_mean and Green_median as key features. ResNet outperformed in deep learning (accuracy 95.23%, sensitivity 84.81%, specificity 97.27%, AUC 0.940).Conclusion The deep learning model shows good value in identifying flap venous insufficiency, serving as an auxiliary tool for postoperative monitoring.

BackgroundOncolytic virotherapy (OVT) represents a promising approach for cancer treatment, employing oncolytic viruses (OVs) that selectively infect and lyse tumor cells while promoting an antitumor immune microenvironment. Vaccinia virus (VACV) serves as an attractive oncolytic vector due to its favorable safety profile, ease of genetic modification, and inherent tumor selectivity.MethodsTo enhance both safety and tumor-targeting capability, we constructed a recombinant vaccinia virus, VV-dTF/EE, by deleting the viral J2R and F4L genes and inserting the human neutrophil elastase (ELANE) gene, which exhibits tumor-killing activity. Mechanistic studies evaluated with virus replication selectivity, cell apoptosis, genomic damage, immunogenic cell death, alongside analysis of the immune microenvironment. Efficacy was tested in multiple tumor cell models in vitro and lung cancer models in vivo.ResultsIn tumor cell lines and mouse tumor models, VV-dTF/EE demonstrated tumor-restricted replication, potent oncolytic effects, and induction of immunogenic cell death. Furthermore, VV-dTF/EE augmented VACV-induced antitumor immunity by increasing CD8+ T cell infiltration and suppressing M2-like macrophage polarization.ConclusionsThis VV-dTF/EE revealed tumor-selective replication and killing ability while modifying the tumor immune microenvironment to elicit immunogenic cell death. Our findings highlight a novel strategy for safe and effective tumor immunotherapy through dual-gene deletion and ELANE expression in an oncolytic vaccinia platform.

Pediatric rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children, exhibits heterogeneous responses to neoadjuvant chemotherapy (NAC), necessitating reliable biomarkers for early prediction. This multicenter study evaluates MRI-derived radiomic features of intratumoral and peritumoral regions to predict NAC response in the largest pediatric RMS cohort to date. A retrospective analysis included 519 RMS patients from three Chinese centers. Radiologists manually segmented tumors and 2-mm peritumoral regions on standardized T1-weighted contrast-enhanced (T1CE) and T2-weighted fat-saturated (T2Fs) MRI sequences. PyRadiomics extracted 1015 radiomic features, with robustness ensured (ICC ≥ 0.80) and predictive features selected via LASSO regression. Twelve XGBoost models (intra-/peritumoral, multisequence) were developed, validated internally/externally, and compared using DeLong’s test, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). SHAP analysis interpreted feature contributions. Clinical variables (age, fusion gene) were assessed for incremental value. The T1CE-based combined intratumoral–peritumoral model (T1CE_IntraPeri2mm) demonstrated the best generalizability, achieving AUCs of 0.917 (training), 0.760 (internal validation), 0.837 (external test1) and 0.843 (external test2). It significantly outperformed intratumoral-only and multisequence fusion models in DeLong, NRI, and IDI analyses (all p < 0.05). The combined clinical-radiomic model did not provide incremental benefit (AUC: 0.843 vs. 0.838, p = 0.891). SHAP analysis indicated that features reflecting peritumoral structural irregularity and enhancement heterogeneity were key predictors of NAC resistance. T1CE-based peritumoral radiomics robustly predicts NAC response in pediatric RMS, emphasizing tumor-microenvironment interactions. This approach offers a non-invasive tool for personalized therapy stratification. This study establishes peritumoral MRI radiomics as a critical predictor of chemotherapy response in pediatric rhabdomyosarcoma, addressing the unmet need for non-invasive biomarkers and advancing precision oncology through tumor-microenvironment interaction analysis in clinical radiology practice.

PURPOSE:The aim of this study was to report 2 cases of dedifferentiated liposarcoma (DDLPS) in the peripharyngeal space and review the relevant literature to summarize its clinical and histopathologic features and therapeutic approaches, especially operative selection and prognosis. METHODS:A comprehensive review of the literature was performed in January 2025 to identify relevant articles using the PubMed database. Sixty patients were included in this study: 2 new cases from Beijing Tongren Hospital in 2018 and 2023, and 58 previously reported cases that occurred between 1979 and 2024 from a systematic review of the literature. We analyzed and summarized the patients' epidemiological data, clinical features, and treatment regimens. The main outcomes were overall survival (OS) and recurrence-free survival (RFS). RESULTS:DDLPS was approximately twice as common in men as in women, with a median age of 61 years (range: 20-86 y). MDM2 amplification was positive in 13 patients (13/14, 92.9%). Nearly all the patients underwent surgical excision (35/36, 97.2%). Almost half of the patients (17/36, 47.2%) underwent surgery with postoperative radiotherapy (RT). The 1-year, 3-year, and 5-year OS rates were 91.3%, 81.2%, and 81.2%, respectively. The 1-year, 3-year, and 5-year RFS rates were 91.3%, 74.9%, and 64.2%, respectively. Local radical excision is the preferred treatment modality for DDLPS. Adjuvant chemoradiotherapy after radical surgery resection had no statistically significant impact on OS or RFS (P˃0.05). CONCLUSIONS:Detection of MDM2 during initial biopsy can prevent delays in diagnosis and treatment. Local radical excision is the preferred treatment modality for DDLPS.

Background The current study presents the efforts of a global collaborative group to review the management and outcomes of malignant tumors of the skull base in the pediatric population worldwide.Patients and Methods A total of 28 institutions contributed data on 3061 patients. From this, there were 64 pediatric patients (2.1%). Clinical variables, overall and disease-free survival (OS and DFS) outcomes, and multivariable factors associated with outcome were evaluated.Results The male-to-female ratio was 37:27 and the median [IQR] age at diagnosis was 14.0 [9.6-16.0] years. The most common malignancy was sarcoma (57.8%), followed by esthesioneuroblastoma (25.0%) and carcinoma (17.2%). Negative margins were achieved in 53.1% children. Dural invasion was associated with reduced OS and DFS. Adjuvant radiotherapy was associated with improved survival outcomes.Conclusions Open approaches were widely used for pediatric skull base tumor resection in the period between 1995 and 2015 but we saw a rise in the use of endoscopic and combined techniques by the end of the period covered by this study. Our results may represent a transitional era in which alternative endoscopic techniques continue to expand.

BACKGROUND:This study aimed to develop predictive models for local (LR), regional (RR), and distant recurrence (DR) after skull base surgery for primary malignant tumors. METHODS:We analyzed 2179 patients (1995-2015) from an international multicenter database, split into training (n = 1297) and validation (n = 882) cohorts. Cox regression identified predictors of LR, RR, and DR, and nomograms were developed and validated using concordance indexes (C-indexes). RESULTS:Median age was 56 years; 64% were male. The most common sites included the ethmoid sinus (38%), nasal cavity (25%), and maxillary sinus (20%). Squamous cell carcinoma was the most frequent histology (25%). LR predictors included brain invasion, higher-risk histology, pT3/T4, pN+, positive margins, and adjuvant therapy (protective). RR predictors included high-risk histology, pT3/T4, and pN+. DR predictors mirrored LR except for adjuvant therapy. C-indexes were around 0.7 for all endpoints. CONCLUSIONS:These validated nomograms provide useful tools for recurrence risk stratification and personalized management.

Neoadjuvant immunotherapy combined with chemotherapy (NICT) improves tumor downstaging in locally advanced hypopharyngeal squamous cell carcinoma (LA-HSCC), but the effect of response-adapted surgery on outcomes is unclear. This study evaluated the efficacy and safety of NICT and compared minimally invasive versus open surgery on the basis of treatment response. We retrospectively analyzed 79 patients with stage III–IVB HSCC who received NICT. Treatment response was assessed per RECIST 1.1, and surgery was tailored accordingly. The objective response rate was 84.81

BACKGROUND:Castleman disease, a rare lymphoproliferative disorder with diverse features, is often misdiagnosed due to rarity and similarity to malignancies. AIMS:The study analyzed the clinicopathological characteristics, diagnostic challenges, and outcomes of head and neck Castleman disease (HNCD) to improve diagnostic accuracy and optimize management strategies. MATERIAL AND METHODS:Retrospective study of 21 HNCD patients treated at Beijing Tongren Hospital (2007-2024). Demographics, presentation, imaging, histopathology, treatment, and outcomes were analyzed using t-tests, Mann-Whitney U, and Fisher's exact tests. RESULTS:Mean age 36.1; 52.4% female. Mainly painless cervical masses (95.2%). Histology: 85.7% hyaline vascular, 14.3% plasma cell. Imaging showing non-specific hypoechoic nodules (ultrasound) and homogeneous enhancement (CT/MRI). Surgical excision (85.7%) achieved 76.2% complete remission (mean follow-up: 85.2 months). Tumor size (34.6 ± 15.3 mm) didn't correlate with outcome (p = 0.756). One plasma cell patient (4.8%) died of unrelated causes. No recurrences or malignant transformations were observed. CONCLUSIONS AND SIGNIFICANCE:HNCDs are predominantly unicentric and can be cured with complete surgical resection. Due to the lack of specificity of imaging and laboratory findings, diagnosis relies on histopathology. Collaborations among multiple centers and molecular studies are essential to advancing the precision treatment of HNCD.

Introduction:Diabetes mellitus (DM) is a known risk factor for various cancers, but its relationship with head and neck squamous cell carcinoma (HNSCC) remains unclear. This study explores clinical and molecular links between DM and HNSCC through integrative analyses of patient data and bioinformatics. Methods:A retrospective cohort of 728 HNSCC patients was analyzed to assess sex-specific co-occurrence with DM. A simulation-based epidemiological model quantified associations based on observed clinical data and population incidence rates. Literature-based data mining was used to extract gene-disease associations for DM and HNSCC, followed by functional enrichment, pathway and network analyses of overlapping genes. Results:The simulation revealed a significant association between DM and HNSCC, stronger in males (Odds Ratio [OR] = 3.03, p = 6.28 × 10-50) than in females (OR = 2.18, p = 8.7 × 10-12). Data mining uncovered 3,489 overlapping genes (OR = 6.73, p < 4.95 × 10-319), including nine key genes (GPX4, NLRP3, CASP3, HOTAIR, SRC, IGF2BP2, APP, CYP2C19, and PVT1) tightly interconnected and functionally enriched in inflammation, metabolism, and neurological signaling pathways. Four genes-CYP2C19, NLRP3, PVT1, and APP-appear central to DM's influence on HNSCC via the protein-protein interaction (PPI) network. Conclusion:These findings reveal a significant clinical and molecular connection between DM and HNSCC, especially in males, and highlight potential targets for future prevention and treatment strategies.

BRAFV600E mutation is the most common genetic change in papillary thyroid carcinoma (PTC). Nevertheless, the association between BRAFV600E mutation status and abundance and the biological behavior of PTC is unclear. Thus, this study investigated whether BRAFV600E mutation status and abundance are related to PTC biological behavior and whether BRAFV600E mutation abundance can be used to further stratify risk. Postoperative formalin-fixed paraffin-embedded (FFPE) specimens from 528 PTC patients formed the retrospective cohort, and preoperative fine-needle aspiration (FNA) specimens from 167 PTC patients formed the prospective cohort. Furthermore, 74 FNA specimens were collected from two additional hospitals to form the external cohort. Droplet digital polymerase chain reaction (ddPCR) was used to detect BRAFV600E mutation status and abundance in the two types of specimens. The relationship between BRAFV600E mutation status and abundance and PTC biological behavior was analyzed in the cohorts. To predict BRAFV600E-positive PTC risk stratification, we constructed postoperative clinicopathological models (Model A, retrospective; Model B, prospective), a preoperative clinical model (Model C), and a fusion model combining BRAFV600E mutation abundance and preoperative clinical information (Model D). The area under the curve (AUC) values were used to assess the performance of these models. Univariate and multivariate analysis of the retrospective, prospective and external cohorts indicated that BRAFV600E mutation abundance, not status, was significantly associated with PTC biological behavior. An increase in BRAFV600E mutation abundance was significantly associated with an increased risk of BRAFV600E-positive PTC. The AUCs of model A, model B, model C, and model D in the validation sets were 0.89 (95 https://www.chictr.org.cn/showproj.html?proj=190478 .

BackgroundAnxiety disorders (AD), ADHD, and head and neck cancer (HNC) are complex conditions with potential genetic interconnections that remain to be fully elucidated. The purpose of this study is to investigate gene-level connections among ADHD, AD, and HNC.MethodA comprehensive literature mining approach identified potential gene-disease relationships from PubMed and bioinformatics databases, analyzing 19,924 genes. An AI-driven computational process constructed a gene-disease relationship table using the Adjusted Binomial Method Algorithm (ABMA) to evaluate association reliability. Overlapping genes were analyzed through protein-protein interaction (PPI) networks, functional annotations, and literature-based pathway analyses to elucidate shared and unique genetic mechanisms linking these diseases.ResultsThe analysis identified 141 significant genes associated with AD, 153 with ADHD, and 1,065 with HNC (q-value < 0.05). These genes demonstrated significant overlap (odds ratio ≥ 1.8; p ≤ 2.58E-2) and high interconnectivity (PPI network density ≥ 0.39, clustering coefficient ≥ 0.76, and diameter ≤ 3). Centrality analysis revealed core genes such as IL-6, MYC, NLRP3, and CXCR4 as critical mediators. Functional enrichment analysis identified key pathways, including serotonergic synapse, inflammatory response, and Toll-like receptor signaling, highlighting the involvement of neuronal and immune mechanisms. Functional pathway analysis demonstrated reciprocal genetic influences among AD, ADHD, and HNC, emphasizing shared and distinct gene-level connections that may underlie their co-occurrence and mutual risk factors.ConclusionThis study reveals a complex and interconnected genetic network among AD, ADHD, and HNC, highlighting shared pathways, unique mechanisms, and critical genes, providing valuable insights into the genetic underpinnings of these conditions and potential avenues for therapeutic exploration.

OBJECTIVES:To explore the potential influence of Sjogren's syndrome (SS) on thyroid cancer (TC). METHODS:First, a literature data mining (LDM) approach was used to reconstruct functional pathways connecting SS and TC. A meta-analysis was then performed to examine the expression changes of genes mediated by SS using 16 TC case/control expression datasets, with results validated through the TCGA/GTEx dataset. Finally, gene set enrichment analysis (GSEA) and survival analysis using GEPIA2 were conducted on the significant genes. RESULTS:Our findings indicate that SS may increase the risk of TC by activating 14 TC promoters (PDCD1, NTRK1, LGALS3, CD274, FOXP3, BCL2, CYP1A1, HMGB1, TGFB1, CCL2, PLA2G7, TFF3, LCN2, and CLDN1) and suppressing three TC inhibitors (MIR145, MIR30C1, and EP300). Four molecules (PLA2G7, TFF3, LCN2, and CLDN1) exhibited significant expression changes in TC patients (LFC > 1 or < -1; p < 2.07E-04), which were confirmed in TCGA/GTEx expression analysis. These results highlight three possible mechanisms-the SS-PLA2G7-CCL2-TC pathway, the SS-LCN2-LGALS3-TC pathway, and the SS-CLDN1-BCL2-TC pathway-that may explain how SS contributes to TC development. Enrichment analysis suggests that SS may affect TC prognosis by regulating leukocytes and tolerance induction. Survival analysis indicates that SS may enhance TC survival through the regulation of the CLDN1 and EGF pathways. CONCLUSION:LDM-based pathway analysis highlighted three genetic pathways through which SS may adversely affect TC progression, while SS may enhance TC survival via the CLDN1 and EGF pathways, highlighting the need for further research.