Background: Psoriasis extends beyond its dermatological inflammatory manifestations, encompassing systemic inflammation. Existing studies have indicated a potential risk of cervical cancer among patients with psoriasis, suggesting a potential mechanism of co-morbidity. This study aims to explore the key genes, pathways, and immune cells that may link psoriasis and cervical squamous cell carcinoma (CESC).Methods: The cervical squamous cell carcinoma dataset (GSE63514) was downloaded from the Gene Expression Omnibus (GEO). Two psoriasis-related datasets (GSE13355 and GSE14905) were merged into one comprehensive dataset after removing batch effects. Differentially expressed genes were identified using Limma and co-expression network analysis (WGCNA), and machine learning random forest algorithm (RF) was used to screen the hub genes. We analyzed relevant gene enrichment pathways using GO and KEGG, and immune cell infiltration in psoriasis and CESC samples using CIBERSORT. The miRNA-mRNA and TFs-mRNA regulatory networks were then constructed using Cytoscape, and the biomarkers for psoriasis and CESC were determined. Potential drug targets were obtained from the cMAP database, and biomarker expression levels in hela and psoriatic cell models were quantified by RT-qPCR.Results: In this study, we identified 27 key genes associated with psoriasis and cervical squamous cell carcinoma. NCAPH, UHRF1, CDCA2, CENPN and MELK were identified as hub genes using the Random Forest machine learning algorithm. Chromosome mitotic region segregation, nucleotide binding and DNA methylation are the major enrichment pathways for common DEGs in the mitotic cell cycle. Then we analyzed immune cell infiltration in psoriasis and cervical squamous cell carcinoma samples using CIBERSORT. Meanwhile, we used the cMAP database to identify ten small molecule compounds that interact with the central gene as drug candidates for treatment. By analyzing miRNA-mRNA and TFs-mRNA regulatory networks, we identified three miRNAs and nine transcription factors closely associated with five key genes and validated their expression in external validation datasets and clinical samples. Finally, we examined the diagnostic effects with ROC curves, and performed experimental validation in hela and psoriatic cell models.Conclusions: We identified five biomarkers, NCAPH, UHRF1, CDCA2, CENPN, and MELK, which may play important roles in the common pathogenesis of psoriasis and cervical squamous cell carcinoma, furthermore predict potential therapeutic agents. These findings open up new perspectives for the diagnosis and treatment of psoriasis and squamous cell carcinoma of the cervix.

Objective: This study aims to analyze adverse drug events (ADE) related to romosozumab from the second quarter of 2019 to the third quarter of 2023 from FAERS database. Methods: The ADE data related to romosozumab from 2019 Q2 to 2023 Q3 were collected. After data normalization, four signal strength quantification algorithms were used: ROR (Reporting Odds Ratios), PRR (Proportional Reporting Ratios), BCPNN (Bayesian Confidence Propagation Neural Network), and EBGM (Empirical Bayesian Geometric Mean). Results: Screening for romosozumab-related AEs (adverse events) included 23 system organ categories (SOCs). PT (preferred terms) levels were screened for adverse drug reaction (ADR) signals. A total of 7055 reports with romosozumab as the primary suspect (PS) and 14,041 PTs induced by romosozumab as PS were identified. Common significant signals of general disorders and administration site conditions, musculoskeletal and connective tissue disorders have emerged. Specifically, unexpected AEs such as gastrointestinal disorder, respiratory, thoracic and mediastinal disorders also occur. Notably, fracture (n = 503, ROR = 107.8, PRR = 103.83, IC = 6.6, EBGM = 97.02) and bone density abnormal (n = 429, ROR = 343.65, PRR = 332.77, IC = 8.08, EBGM = 271.34) exhibited relatively high occurrence rates and signal strengths. Conclusion: Our study identifies potential new AE signals and provides broader data support for the safety of romosozumab. In clinical application, doctors are provided with a warning to closely monitor adverse reactions to support their rational use in diseases such as osteoporosis.

Background: Progesterone and adipose Q receptor 5 (PAQR5), a membrane receptor characterized by seven transmembrane domains, has been indirectly implicated in pro-carcinogenic activities, though its specific role in hepatocellular carcinoma (HCC) remains to be defined. Methods: This study aimed to elucidate the molecular mechanisms by which PAQR5 facilitates HCC progression and contributes to the immunosuppressive microenvironment through an integrative approach combining multi-omics analysis and experimental validation. Utilizing data from bulk, single-cell, and spatial transcriptomics cohorts, this study systematically assessed the expression patterns, immune landscape, and functional characteristics of PAQR5 across different levels of resolution in HCC. Results: PAQR5 expression was significantly upregulated in tumor tissues and correlated with poor clinical outcomes. Enrichment analysis revealed that PAQR5 activated the NF-κB signaling pathway in HCC. Single-cell transcriptomics identified PAQR5 as predominantly localized within malignant cell clusters, with significant association with NF-κB pathway activation. Spatial transcriptomics further corroborated the alignment of PAQR5 expression with tumor cell distribution. In vitro assays showed elevated PAQR5 levels in HCC cell lines, and silencing PAQR5 significantly suppressed cell proliferation, invasion, epithelial-mesenchymal transition (EMT), and prevented the formation of immunosuppressive microenvironment. In vivo studies demonstrated that targeting PAQR5 attenuated tumorigenic potential, disrupted the invasion-metastasis cascade and inhibited the tumor immune escape. Mechanistically, PAQR5 was found to activate NF-κB signaling by inducing ERK phosphorylation, thereby driving proliferation, invasion, EMT, and immune escape in HCC through the pathway.

Background: Colon adenocarcinoma (COAD) is a lethal malignancy with a poor prognosis. The tumor microenvironment (TME) is pivotal in its development, within which lactate accumulation is a common metabolic hallmark. Lactylation, a novel post-translational modification driven by lactate, serves as a crucial link between tumor metabolism and immunosuppression. It plays multifaceted roles in promoting malignant progression, immune evasion, and chemoresistance. Therefore, systematically investigating lactylation and identifying its key mediators may yield novel therapeutic targets and strategies for COAD. Methods: We performed an integrative multi-omics analysis of lactylation-related genes (LRGs) in COAD and pan-cancer cohorts, leveraging bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic data from public repositories including TCGA and GEO. A curated set of 160 LRGs was investigated using a multi-step machine learning framework, integrating Cox regression, time-dependent ROC analysis, and optimal risk stratification to construct robust prognostic signatures, which collectively identified AARS2 as a pivotal candidate. Subsequent multi-faceted oncogenic characterization of AARS2 encompassed its expression profiles, diagnostic and prognostic value, and associations with tumor microenvironment heterogeneity. To validate AARS2 at the protein level, we first interrogated the HPA database and subsequently confirmed its expression using immunohistochemistry (IHC) on an independent cohort of clinical COAD specimens. To further elucidate AARS2’s functional role in COAD pathogenesis and its potential linkage to lactylation biology, in vitro validation was performed using the human COAD cell line HCT116. AARS2 expression was confirmed at both protein (Western blot) and mRNA (qRT-PCR) levels. qRT-PCR additionally quantified transcriptional changes in immune-related genes (CCL5, CXCL10, IFNB1), while extracellular lactate accumulation was measured to assess AARS2-associated metabolic alterations. All statistical analyses were performed in R, with a significance threshold of p < 0.05. Results: Integrative multi-omics analyses identified AARS2 as significantly upregulated in COAD and multiple malignancies, with elevated expression correlating with adverse clinical outcomes. Single-cell and spatial transcriptomic profiling indicated predominant enrichment of AARS2 in malignant cell populations and association with immunosuppressive microenvironment features. Functional enrichment suggested potential involvement in epithelial–mesenchymal transition, hypoxia response, and cell cycle pathways. Immunohistochemical validation in clinical COAD specimens confirmed higher AARS2 protein levels in tumor tissues versus adjacent normal mucosa; concurrent elevation of cGAS protein was observed, though functional activity requires contextual interpretation. In vitro studies in HCT116 cells revealed that AARS2 knockdown reduced extracellular lactate accumulation and attenuated global protein lactylation. Concomitantly, transcriptional upregulation of cGAS–STING pathway-associated genes (CCL5, CXCL10, IFNB1) was observed following AARS2 silencing. These correlative findings suggest a potential nexus between AARS2, lactate metabolism, protein lactylation dynamics, and innate immune signaling modulation in COAD. Conclusion: AARS2 correlates with lactylation dynamics, metabolic features, and immune modulation in COAD, suggesting a potential role in lactylation-associated cGAS–STING pathway regulation. These correlative observations warrant rigorous mechanistic validation to define causality and assess translational potential.