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PubMed2026

Proteomics in environmental pollution research: Advances, challenges, and future directions.

Environmental proteomics has emerged as a powerful approach for elucidating the molecular mechanisms underlying pollutant-induced biological effects. Although this field has developed rapidly, the systematic review of recent proteomics applications in environmental pollution research remains limited. This review explored the emerging roles of toxicoproteomics in biomarker discovery and mechanistic elucidation, as well as ecotoxicoproteomics in ecological risk assessment and bioremediation strategies. Here, we review the field, highlighting recent trends such as the integration of proteomics with genomics, transcriptomics, and metabolomics to provide a comprehensive view of biological responses to environmental stressors. We further discuss the growing application of artificial intelligence in improving proteomics data interpretation and accelerating biomarker discovery. In addition, recent technological advances in environmental proteomics are highlighted, including next-generation tissue microarray proteomics, nanoscale proteomics, single-cell proteomics, and spatial proteomics. Despite its potential, proteomics faces challenges, such as high operational costs, computational complexity in analysis, and technical limitations in low-abundance protein detection. We propose that the convergence of proteomics with artificial intelligence and multi-omics approaches offers promising solutions to these challenges, enhancing the practical application of proteomics in environmental monitoring and risk assessment.

Proteomics↗

PubMed2026

MicroRNA-155 modulates STAT3 signaling by targeting KPNA1 in chronic chorioamnionitis of human placenta.

Chronic chorioamnionitis (CCA) is a placental inflammatory lesion characterized by maternal T cell infiltration and trophoblast apoptosis, resembling allograft rejection. MicroRNA-155 (miR-155) is a central regulator of immune and inflammatory pathways, but its role in CCA remains unclear. This study investigated whether miR-155 contributes to the pathogenesis of CCA by targeting karyopherin α1 (KPNA1) and modulating STAT3 signaling in human trophoblasts. Placental tissues from 28 CCA cases and 16 gestational age-matched controls were analyzed for miR-155 expression using quantitative RT-PCR and in situ hybridization. Functional assays were conducted in Swan 71 trophoblast cells following miR-155 overexpression and siRNA-mediated KPNA1 knockdown. Microarray and qRT-PCR analyses identified gene expression changes, while western blotting and dual-luciferase reporter assays were conducted to evaluate STAT3 activity and direct target binding. miR-155 expression was significantly elevated in CCA fetal membranes. KPNA1 was identified as a direct target of miR-155, and its suppression reduced STAT3 phosphorylation and nuclear translocation. Dual-luciferase assays confirmed that miR-155 binds to the 3' untranslated region of KPNA1 mRNA, thereby inhibiting its translation. These findings suggest that miR-155 downregulates KPNA1, leading to inhibition of STAT3 signaling in trophoblasts, which may contribute to maternal-fetal immune dysregulation and trophoblast apoptosis in CCA. The miR-155-KPNA1-STAT3 axis may represent a potential therapeutic target in pregnancy-related inflammatory disorders.

Humans↗

PubMed2026

Molecular diagnostic tests for isoniazid-resistant tuberculosis: a scoping review.

The paucity of diagnostic tests for isoniazid-resistant tuberculosis is concerning, given its status as the most common form of drug-resistant tuberculosis and a gateway to multidrug-resistant diseases. Molecular drug-susceptibility testing has improved access to timely diagnosis of rifampicin-resistant tuberculosis, but testing for isoniazid-resistant tuberculosis still remains rare. In this Review, we assessed the characteristics of molecular drug-susceptibility testing for detection of isoniazid-resistant tuberculosis, referencing the WHO target product profiles. 9243 citations were screened to select 238 studies published between 2000 and 2024. The diagnostics options have expanded rapidly since 2020, with 27 nucleic acid amplification tests, eight line probe assays, five DNA microarrays, two targeted next-generation sequencing platforms, and two whole-genome sequencing platforms. Most of the evaluated molecular drug-susceptibility tests met diagnostic performance targets but were often complex and costly. Although a few low-complexity nucleic acid amplification tests met key target product profile criteria, additional field validation and greater efforts are needed to ensure optimal feasibility and affordability for low-resource settings.

Isoniazid↗

PubMed2026

Global downstream BMP15 pathway analysis in human ovarian granulosa cells reveals novel genetic variations associated with primary ovarian insufficiency.

OBJECTIVES: Primary ovarian insufficiency (POI) is a fertility disorder with a well-established genetic component, but many cases still remain idiopathic. Approximately 1.5-12% of patients with POI can carry a variant in the BMP15 gene, depending on the population and the diagnostic criteria. We hypothesize that genetic variations within pathways downstream of BMP15 activity in ovarian granulosa cells (GCs) may contribute to unexplained cases of POI. The main goal of this study is to identify novel variants associated with POI in genes induced by BMP15 in GCs. STUDY DESIGN: Primary cultures of human GCs were stimulated with recombinant human BMP15. Microarray analysis profiled the BMP15-induced transcriptome in GCs. Validation was achieved by qPCR and immunoblot. Further, target exome sequencing of the differentially expressed genes was performed on 64 women with early POI onset in search of novel variants. MAIN OUTCOME MEASURES: Transcriptome profiling of human GCs stimulated with BMP15 and target exome sequencing in women with early onset of POI. RESULTS: Transcriptome analysis revealed significant upregulation of 19 genes (p < 0.05). Ontology analysis of these genes converged towards two main pathways: TGF-beta signaling and regulation of stem cell pluripotency. Target exome sequencing identified six novel rare variants in five BMP15-induced genes (SAMD11, SMAD6, ID1, USP35, GPCR137C) in 9 of the 64 women with early POI (14%). CONCLUSIONS: BMP15 action in human ovarian GCs defines TGF-beta signaling and pluripotency fate in ovarian follicles. In addition, this study uncovers new potential candidate genes for the pathogenesis of POI.

Humans↗

PubMed2024

Proteomic Heterogeneity of the Extracellular Matrix Identifies Histologic Subtype-Specific Fibroblast in Gastric Cancer.

Gastric cancer (GC) is a highly heterogeneous disease regarding histologic features, genotypes, and molecular phenotypes. Here, we investigate extracellular matrix (ECM)-centric analysis, examining its association with histologic subtypes and patient prognosis in human GC. We performed quantitative proteomic analysis of decellularized GC tissues that characterizes tumorous ECM, highlighting proteomic heterogeneity in ECM components. We identified 20 tumor-enriched proteins including four glycoproteins, serpin family H member 1 (SERPINH1), annexin family (ANXA3/4/5/13), S100A family (S100A6/8/9), MMP14, and other matrisome-associated proteins. In addition, histopathological characteristics of GC reveals differential expression in ECM composition, with the poorly cohesive carcinoma-not otherwise specified (PCC-NOS) subtype being distinctly demarcated from other histologic subtypes. Integrating ECM proteomics with single-cell RNA sequencing, we identified crucial molecular markers in the PCC-NOS-specific stroma. PCC-NOS-enriched matrisome proteins and gene expression signatures of adipogenic cancer-associated fibroblasts (CAFadi) are closely linked, both associated with adverse outcomes in GC. Using tumor microarray analysis, we confirmed the CAFadi surface marker, ATP binding cassette subfamily A member 8 (ABCA8), predominantly present in PCC-NOS tumors. Our ECM-focused analysis paves the way for studies to determine their utility as biomarkers for patient stratification, offering valuable insights for linking molecular and histologic features in GC.

Humans↗

PubMed2025

Clinicopathologic and Genomic Characterization of SMARCA4-Deficient Carcinoma of the Gallbladder.

As a key subunit of the SWItch/sucrose nonfermentable chromatin-remodeling complex, SMARCA4 plays a critical role as a tumor suppressor in various tumors. However, the clinicopathological and molecular features of SMARCA4-deficient carcinoma of the gallbladder (SMARCA4-dGBC) have not been well explored. In this study, a retrospective cohort of 926 nonsquamous cell gallbladder carcinomas (GBCs) was analyzed on tissue microarrays using immunohistochemistry for SMARCA4, comprising 813 adenocarcinomas, 53 adenosquamous carcinomas, 43 undifferentiated carcinomas, 7 sarcomatoid carcinomas, 6 small cell neuroendocrine carcinomas, and 4 large cell neuroendocrine carcinomas. Twenty-six (2.8%) SMARCA4-dGBCs were identified and further analyzed using immunohistochemistry, whole-exome sequencing, and clinicopathological data. SMARCA4-dGBCs are frequently identified in advanced stages and exhibit diverse patterns of differentiation. The majority were identified as monotonous diffuse sheets, nests, and cords, whereas a subset exhibited gland-forming and rhabdoid morphologies (11.5%). Tumors retained mismatch repair proficiency (100%) but showed variable HER2 expression (11.5% scored as 2+/3+) and limited PD-L1 positivity. Genomic profiling revealed SMARCA4 alterations in 88.5% (23/26) of patients, predominantly deletions (91.3%) and truncating mutations-p.K892∗ and p.R979∗-that disrupt the critical ATPase/helicase domains. Co-occurring TP53 mutations (56.5%) highlighted the presence of synergistic chromatin-remodeling defects. Enrichment of oncogenic signaling pathways, including the RTK-RAS (78.3%), TP53 (60.9%), NOTCH (47.8%), and HIPPO (39.1%) pathways, was observed. Patients with SMARCA4-dGBC exhibited significantly shorter progression-free survival (median, 6 vs 14 months) and overall survival (median, 11 vs 16 months) than those with SMARCA4-retained tumors. Overall, these findings revealed that SMARCA4-dGBC is a rare, distinct entity characterized by the destabilization of the SWItch/sucrose nonfermentable complex, genomic instability, and resistance to conventional therapies. The prevalence of targetable pathways, such as RTK-RAS and cell cycle dysregulation, highlights opportunities for precise therapeutic strategies involving EZH2, CDK4/6, or ATR inhibitors. SMARCA4 immunohistochemistry and molecular profiling are essential for accurate diagnosis, prognostic stratification, and therapeutic innovation of this GBC subtype.

Humans↗

PubMed2026

Multi-omics and experimental validation identify RAPGEF2 as a protective prognostic biomarker in clear cell renal cell carcinoma.

Kidney Renal Clear Cell Carcinoma (KIRC) is characterized by marked molecular heterogeneity and metabolic reprogramming, underscoring the need for reliable biomarkers for prognostic assessment and individualized treatment. RAPGEF2, a guanine nucleotide exchange factor has been implicated in cell adhesion and differentiation, but its role in KIRC remains unclear. In this study, we systematically evaluated the expression pattern, prognostic significance, genomic associations, biological function, and therapeutic relevance of RAPGEF2 in KIRC through integrated multi-omics analyses and experimental validation. Pan-cancer single-cell and Spatial transcriptomic analysis revealed heterogeneous RAPGEF2 expression across tumor types, with a relatively prominent signal in KIRC, where RAPGEF2 was mainly enriched in endothelial cells. Survival analyses in the TCGA-KIRC showed that high RAPGEF2 expression was significantly associated with favorable overall survival, disease-specific survival, and progression-free interval, and these findings were validated in independent ICGC_RECA-EU and E-MTAB-1980 cohorts. Multivariate Cox regression further confirmed RAPGEF2 as an independent protective prognostic factor. Immunohistochemistry in a tissue microarray cohort demonstrated that higher RAPGEF2 protein expression was associated with improved overall survival. Genomic analyses showed that low RAPGEF2 expression was related to higher mutational burden. Functional assays demonstrated that RAPGEF2 knockdown promoted KIRC progression. Enrichment analyses indicated that RAPGEF2 may be associated with metabolic pathway remodeling, while immunotherapy cohort analyses suggested its potential association with therapeutic benefit. Collectively, RAPGEF2 is identified as a protective prognostic biomarker and potential functional regulator in KIRC.

Biomarker↗

PubMed2026

Integrated expression profiling of trophoblast cell-surface antigen 2 (TROP2), folate receptor alpha (FRα), and human epidermal growth factor receptor 2 (HER2) in endometrial Cancer across molecular classes, genomic alterations, and histologic subtypes.

OBJECTIVE: Antibody-drug conjugates (ADCs) are expanding treatment options in endometrial carcinoma, but the distribution of actionable surface targets across histologic, molecular, and genomic subgroups remains incompletely defined. METHODS: This single-institution retrospective tissue microarray (TMA) study included 312 endometrial carcinomas: 158 endometrioid and 154 serous tumors. Trophoblast cell-surface antigen 2 (TROP2) was quantified by histochemical score (H-score); human epidermal growth factor receptor 2 (HER2) was assessed using endometrial carcinoma-specific and gastric/DESTINY-PanTumor02 criteria; and folate receptor alpha (FRα) positivity was defined as ≥75% viable tumor cells with ≥2+ membranous staining. Molecular class was assigned using a hierarchical DNA polymerase epsilon (POLE)-mutant, microsatellite instability/mismatch repair-deficient (MSI/MMRd), p53-abnormal, and no specific molecular profile (NSMP) classifier. Tumor mutational burden (TMB) and recurrent genomic alterations were analyzed in relation to biomarker expression. RESULTS: TROP2 was broadly expressed, with median H-scores of 280 in endometrioid and 200 in serous carcinomas. HER2 gastric-score 2+/3+ expression and FRα positivity were enriched in serous versus endometrioid carcinoma (22.5% vs 8.9% and 20.1% vs 4.4%), restricted to FIGO grade 3 tumors, and concentrated in p53-abnormal disease. FRα positivity was absent in POLE-mutant and MSI/MMRd tumors. HER2 2+/3+ expression correlated with erb-b2 receptor tyrosine kinase 2 (ERBB2) alterations, whereas FRα-positive tumors were enriched for TP53 alterations and showed lower frequencies of ARID1A and PTEN alterations. Triple-negative TROP2/HER2/FRα tumors were uncommon (6/308, 1.9%). CONCLUSIONS: TROP2 is broadly expressed in endometrial carcinoma, whereas HER2 and FRα define a more restricted high-grade, serous/serous-like, p53-abnormal compartment, supporting biomarker-informed ADC development.

Humans↗

PubMed2026

Hyperlactate-Associated Lysine Lactylome Remodeling in Laryngeal Squamous Cell Carcinoma.

Laryngeal squamous cell carcinoma (LSCC) lacks reliable biomarkers, and the roles of lactate metabolism and lysine lactylation (Kla) remain largely unknown. We profiled the lysine lactylome of LSCC, paired it with adjacent normal tissues, and integrated the data with quantitative proteomic and transcriptomic analyses. LSCC exhibited a hyperlactate-associated phenotype characterized by dysregulated lactate-related genes (LRGs), altered protein abundance, increased tissue lactate, and globally increased Kla levels. Data-independent acquisition mass spectrometry (DIA-MS) identified 1616 Kla sites on 1468 peptides from 688 proteins, with most differential sites being upregulated in tumors. Differentially lactylated proteins were enriched in cell-matrix adhesion, cell migration, chromatin remodeling, and gene-regulatory processes and were clustered into cytoskeletal and nuclear regulatory modules. Multiple Kla sites were also detected on the core histones. Immunoblotting and tissue microarray analyses confirmed increased pan-Kla expression in the LSCC. Pan-Kla levels were independent of sex and age but positively correlated with the tumor stage and lymph-node metastasis. These findings provide a systematic resource for hyperlactate-associated lactylome remodeling in LSCCs and identify candidate Kla-related molecular features associated with clinicopathological progression for future functional and clinical evaluation.

Humans↗

PubMed2026

Persistent tic disorders are associated with 17q12 duplications.

Tourette Syndrome (TS) and Persistent Tic Disorder (PTD) are childhood-onset neuropsychiatric conditions with high heritability. Due to current sample size limitations, identifying TS/PTD risk genes has been challenging. This study addressed this issue by conducting a meta-analysis of microarray copy number variant (CNV) studies from three TS/PTD genomics consortia, supplemented with new data from 3291 cases. This approach more than doubled the sample size of previous TS/PTD CNV studies, with CNV calls generated from 5725 TS/PTD cases and 10,982 matched controls. The results confirmed that TS/PTD cases 1) have a higher burden of ultra-rare deletions overlapping loss-of-function intolerant genes (OR = 1.68, P = 9.3×10-5) and 2) are more likely to carry established neurodevelopmental CNVs (OR = 1.42, P = 3.9×10-2) compared to controls. Additionally, a novel, genome-wide significant CNV locus for TS/PTD was discovered, involving duplications at 17q12 (hg19 chr17:34.8 - 36.2 Mb). This locus is associated with a known duplication syndrome associated with variable neuropsychiatric traits, but has not been previously linked to tic disorders. Eight cases and one control carried the canonical ~1.4 Mb duplication at chr17:34.8-36.2 Mb, while one additional case had a smaller 110 kb duplication within this known CNV that included only one gene, ACACA (acetyl-CoA carboxylase, OR = 26.7, P = 5.69×10-7). Overall, this study provides further evidence that rare, genic CNVs play a substantial role in the genetic architecture of TS/PTD and identifies a new genome-wide significant association with this neurodevelopmental disorder.

Journal Article↗

PubMed2025

Acute Changes in Rat Tissue Gene Expression Following Exposure to Flight Relevant Hypobaria.

Aeromedical evacuation (AE) is an invaluable tool for the transport of critically injured patients to care facilities. There is increasing evidence obtained from animal models and human patients that exposure to AE-relevant hypobaria within a few days of injury can worsen outcomes. The cause of this secondary injury is not well understood but it may be related to changes in gene expression induced by exposure to evacuation-relevant conditions. In order to explore the causes of secondary injury, gene expression induced by AE-relevant flight conditions was analyzed. Adult male rats were exposed to flight cabin-relevant hypobaria (8000 or 4000 ft equivalents) and/or different oxygen concentrations (21% or 100%) for 5 or 10 hr. At the end of the exposures, RNA was isolated from lung, blood, heart, and brain (hippocampus), levels of gene expression were measured via microarray analysis, and canonical pathway analysis identified the primary gene pathways enriched by the exposures. This information should be useful to not only optimize the health status of trauma patients undergoing aeromedical evacuation but also help determine which gene expression pathways could be modulated to optimize the therapeutic efficacy of the body's endogenous protection and repair mechanisms.

Animals↗

PubMed2025

Bioinformatic analyses and validated experiments reveal an aging hallmark gene set and protective miR of coronary artery disease.

To investigate how aging hallmarks exert roles in the age-related disease of coronary artery disease (CAD). R software and the GEO2R online tool identified differentially expressed genes (DEGs) and differentially expressed microRNAs (DEMis) in CAD microarray datasets from the Gene Expression Omnibus. Genes common to target genes of DEMis, DEGs, and an aging gene list from Human Aging Genomic Resources were then identified and analyzed for protein-protein interactions and functional and pathway enrichment. An miR-mRNA network was constructed using Cytoscape. Receiver operating characteristic curve analysis assessed the diagnostic utility of DEMis in CAD. The expression of two DEMis from a CAD cohort was employed to validate the findings. An aging hallmark gene set, comprising 18 genes, was delineated, with the hub gene TP53 established through protein-protein interaction and microRNA-mRNA networks. Within the microRNA-mRNA network, two DEMis (hsa-miR-423-5p and hsa-miR-564) potentially regulated TP53, rendering them potential CAD biomarkers, as indicated by their area under the curves (AUC) surpassing 0.6. Validation experiments corroborated an AUC of 0.7002 for hsa-miR-423-5p and 0.7261 for hsa-miR-564, highlighting its protective association with CAD. Combining hsa-miR-423-5p, hsa-miR-564, total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), white blood cells (WBC) achieved an area under the receiver operating characteristics curve of 0.783. A CAD-associated gene set was identified, with TP53 as the central hub. Hsa-miR-564 emerged as a potential protective factor against CAD.

Humans↗

PubMed2026

TFAP2B and FOXC1 are associated with biologically and clinically distinct differentiation states in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) comprises biologically distinct subtypes, including luminal androgen receptor (LAR) tumors, but routine immunohistochemical markers incompletely capture lineage-associated differentiation states. We investigated TFAP2B, an AP-2 family transcription factor linked to epithelial differentiation, and FOXC1, a basal-like-associated transcription factor, as complementary markers of luminal and basal differentiation in TNBC. In a tissue microarray of 105 TNBCs, tumors were stratified as TFAP2B-dominant, FOXC1-dominant, or double-negative according to relative marker predominance and characterized using lineage, proliferation, molecular, immune, and chemotherapy-response parameters. TFAP2B-dominant tumors were associated with a coherent luminal phenotype, including apocrine/lobular enrichment, strong MUCL1 and AR expression, high CK18, low SOX10, reduced proliferation, frequent wild-type p53 patterns and retained RB1 expression, and low PD-L1 expression. FOXC1-dominant tumors showed contrasting basal-like features. These associations were independently supported at the transcriptional and genomic levels in the METABRIC TNBC cohort. FOXC1-dominant tumors also showed more frequent chemotherapy-induced downstaging than TFAP2B-dominant tumors. Together, we identify TFAP2B as a marker associated with luminal differentiation in TNBC and support combined TFAP2B/FOXC1 assessment as a practical framework for identifying clinically relevant TNBC differentiation states.

Humans↗

PubMed2026

High-throughput single-cell proteomics and transcriptomics from same cells with a nanoliter-scale, spin-transfer approach.

Single-cell multiomic platforms provide a comprehensive snapshot of cellular states and cell types by offering critical insights into the spatiotemporal regulation of biomolecular networks at a systems level, thereby defining the basis of multicellularity. Here, we introduce nanoSPINS, an advanced platform that enables high-throughput profiling and integrative analysis of the transcriptome and proteome from the same single cells using RNA sequencing and isobaric labeling LC-MS-based proteomics, respectively. NanoSPINS can efficiently transfer mRNA-containing droplets across two microarrays via a centrifugation-based approach, while proteins are retained on the initial platform. Benchmarking of nanoSPINS on two cell lines demonstrates its ability to generate global proteomic and transcriptomic profiles that align well with previously established methodologies/platforms. The incorporation of isobaric TMTpro labeling into this single-cell multiomics platform significantly enhances the throughput of single-cell proteomic analyses. Through the high-throughput quantification of the proteome and transcriptome, nanoSPINS not only facilitates the identification of molecular features at both mRNA and protein level but also provides larger sample sizes for improved statistical power in clustering and differential abundance. Given the broad applicability of single-cell multiomics in biological research and clinical settings, we believe nanoSPINS represents a powerful platform for the characterization of heterogeneous cell populations.

Single-Cell Analysis↗

PubMed2026

Carrot Juice Intake Modulates Oncogenic and Inflammatory Pathways in Advanced Colorectal Adenomas: A Pilot Feasibility Study.

Carrots are a rich dietary source of carotenoids and polyacetylenes, bioactive compounds with demonstrated anti-inflammatory and anticancer properties in experimental models. Epidemiological evidence suggests that carrot consumption is associated with a reduced risk of colorectal cancer; however, clinical data linking carrot intake to molecular changes in premalignant colorectal tissue remain limited. In this pilot intervention study, 20 patients with advanced colorectal adenomas were enrolled. Fifteen participants consumed carrot juice daily for 21 days, while five served as untreated controls. Paired adenoma biopsies were collected before and after the intervention and were analyzed using gene expression microarrays to assess transcriptional responses. Carrot juice intake was well tolerated, with adherence exceeding 95% and no reported adverse events. Transcriptomic analysis revealed modulation of key pathways implicated in colorectal carcinogenesis, including downregulation of the WNT, PI3K-AKT, and MAPK signaling pathways, as well as cyclooxygenase-2-related inflammatory pathways and cytokine signaling. These changes were consistent with reduced oncogenic signaling and attenuation of inflammatory activity within adenoma tissue. In summary, short-term carrot juice consumption was associated with coordinated suppression of molecular pathways involved in colorectal adenoma progression. These findings provide preliminary clinical evidence that a whole-food dietary intervention may influence early carcinogenic processes and support the need for larger controlled studies evaluating clinical outcomes.

Journal Article↗

PubMed2025

Identification of multicohort-based predictive signature for NMIBC recurrence reveals SDCBP as a novel oncogene in bladder cancer.

BACKGROUND: Despite surgical and intravesical chemotherapy interventions, non-muscle invasive bladder cancer (NMIBC) poses a high risk of recurrence, which significantly impacts patient survival. Traditional clinical characteristics alone are inadequate for accurately assessing the risk of NMIBC recurrence, necessitating the development of novel predictive tools. METHODS: We analyzed microarray data of NMIBC samples obtained from the ArrayExpress and GEO databases. LASSO regression was utilized to develop the predictive signature. We combined gene signature and clinicopathological factors to construct a clinical nomogram for estimating NMIBC recurrence in a local cohort. Finally. the biological functions and potential mechanisms of SDCBP in bladder cancer were investigated experimentally in vitro and in vivo. RESULTS: An 8-gene signature was developed, and its efficiency for predicting NMIBC recurrence was evaluated using Kaplan-Meier and time-dependent ROC curves in both training and validation datasets. Immunohistochemical testing revealed elevated levels of ACTN4 and SDCBP in recurrent NMIBC tissues. We integrated the two proteins with clinical factors to develop a nomogram model, which showed superior accuracy compared to individual parameters. Gene Set Variation Analysis and Gene Set Enrichment Analysis unveiled SDCBP exerted cancer-promoting biological processes, such as angiogenesis, EMT, metastasis and proliferation. Experimental procedures demonstrated that silencing SDCBP attenuated cell growth, glucose metabolism and extracellular acidification rate, accompanied by decreased expression of p-AKT, p-ERK1/2, LDHA and Vimentin. CONCLUSIONS: The established 8-gene signature holds promise as a tool for predicting NMIBC recurrence, while targeting SDCBP may represent a potential strategy for delaying disease relapse.

Urinary Bladder Neoplasms↗

PubMed2025

Experimental study on the role and biomarker potential of CX3CR1 in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disorder marked by progressive degeneration of articular cartilage and the formation of secondary osteophytes. Despite extensive research, the underlying molecular mechanisms remain poorly understood. This study aimed to identify OA-associated genes and elucidate the molecular pathways implicated, with the goal of discovering reliable diagnostic biomarkers. METHODS: The microarray dataset was retrieved from the Gene Expression Omnibus (GEO) and analyzed using R software to identify the signature gene, CX3CR1. Differentially expressed genes (DEGs) correlated with CX3CR1 were subsequently subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and immune infiltration analyses. A ceRNA regulatory network was also constructed. Vali-dation of CX3CR1 expression was conducted through qRT-PCR, Western blotting, and immunohistochemistry. RESULTS: CX3CR1 emerged as a candidate gene significantly associated with OA, exhibiting regulatory roles primarily in lipid metabolism-related and extra-cellular matrix-related biological processes and signaling cascades. The infiltration levels of immune cells, particularly activated mast cells, appeared to modulate OA progression. Both in vitro and in vivo experiments demonstrated elevated CX3CR1 expression in OA tissues relative to controls, with a robust positive correlation observed between CX3CR1 and MMP13 levels. CONCLUSION: CX3CR1 represents a potential biomarker for OA diagnosis and therapeutic targeting, exerting its effects by modulating lipid metabolism, extracellular matrix dynamics, and immune cell infiltration.

CX3C Chemokine Receptor 1↗

PubMed2026

Profiling tumor immune microenvironment of epithelial ovarian carcinoma.

BACKGROUND: Epithelial ovarian carcinoma (EOC) comprises five main histological subtypes: high-grade serous (HGSOC), low-grade serous (LGSOC), clear cell (CCOC), mucinous (MOC), and endometrioid (ENOC). Each histotype harbors specific genomic alterations and clinical outcome. Few studies systematically compared the tumor immune microenvironment across the five subtypes. METHODS: We performed 7-plex (CD45, CD8, CD68, CD163, FoxP3, CD20, and cytokeratin) sequential immunohistochemistry on a clinically annotated tissue microarray including 139 EOC representing the five subtypes and 26 borderline tumors (serous and mucinous). Digital pathology was used to quantify immune cell abundance, their spatial distribution (stroma vs tumor core), and correlation with survival. RESULTS: Immune cells were dominated by macrophages and more abundant in the stroma than tumor core across the five subtypes, consistent with immune excluded pattern. Compared to HGSOC, CCOC displayed the highest infiltration by CD45+ leukocytes and CD68+ macrophages, particularly M2-like CD163+ cells, suggesting a macrophage-rich, immunosuppressive phenotype. LGSOC exhibited the highest infiltration by intraepithelial FoxP3+ regulatory T cells. Comparison of borderline tumors with invasive carcinoma (LGOSC and MOC) revealed that malignant progression is accompanied by loss of CD8+ T cells, enrichment in regulatory T cells and increase of CD163+/CD68+ ratio, consistent with immune evasion during tumorigenesis. There was a trend toward better survival in HGSOC highly infiltrated by lymphocytes, either intraepithelial (CD8+ and FoxP3+) or stromal (FoxP3+ and CD20+). CONCLUSIONS: EOC is characterized by histotype-specific immune milieux defined by macrophage dominance, epithelial immune exclusion and dynamic immune remodeling during progression from borderline tumors to invasive carcinomas.

Humans↗