Human LRRC15-coupled Magnetic Beads

Abstract: Pancreatic stellate cells (PSCs) contribute to pancreatic ductal adenocarcinoma (PDAC) progression and therapeutic resistance, yet their detailed functions remain unclear. This study combined RNA sequencing and assay for transposase-accessible chromatin using sequencing (ATAC-seq) on sorted PSCs from adjacent normal and PDAC tissues to investigate their transcriptional and epigenetic activation. PSCs heterogeneity and functions are characterized through bulk, single-cell, and spatial transcriptomes, as well as in situ sequencing. The clinical relevance of PSCs in immunotherapy is assessed using an in-house immune-checkpoint blockade (ICB) treatment cohort. Findings showed that stress and hypoxia signaling activated PSCs in PDAC. Three common PSCs (CPSCs) and four tumor-associated PSCs (TPSCs) are identified, each with distinct functions. CPSCs differentiated into CCL19+ TPSCs in immune-enriched regions, MYH11+ TPSCs in the stromal region, and PLXDC1+ TPSCs, which exhibited cancer-associated myofibroblasts (myCAFs) phenotype linked to poor prognosis. Notably, PLXDC1+ TPSCs, located near aggressive LRRC15+ myCAFs and SPP1+ macrophages, formed a desmoplastic and immunosuppressive niche around the tumor boundary, promoting CD8 T cell exhaustion. Single-cell transcriptomics of PDAC patients treated with ICB revealed that PLXDC1+ TPSCs correlated with poor immunotherapy efficacy. Overall, this study provides key insights into PSCs in PDAC and potential therapeutic targets.© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.

Abstract: Friend Leukemia Integration 1 Transcription Factor (FLI1) has attracted attention due to its involvement in rheumatoid arthritis (RA). Nevertheless, the precise mechanism through which FLI1 contributes to RA remains elusive. We investigated the potential role of FLI1 in RA through integrated bioinformatics, clinical experiments, and cellular experiments.Based on the GSE1919 and GSE12021 datasets, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses identified FLI1 as a differential gene in RA. Clinical validation was performed by measuring the FLI1 expression in the serum collected from RA patients. Correlational analysis between FLI1 and immune-inflammatory markers confirmed its association with RA inflammation. WGCNA analysis, along with the KnockTF, JASPAR, and ENCODE databases, was employed to predict the potential target genes of FLI1. Receiver operating characteristic analysis and gene-set enrichment analysis-KEGG were conducted to elucidate the biological functions of these target genes. Finally, cellular experiments were performed to validate FLI1's regulatory effects on its target genes and its impact on synovial cell viability and apoptosis in RA.FLI1 was upregulated in RA. FLI1 exhibited positive correlations with CRP, ESR, CCP, RF, IL-6, IL-10, IL-8, and TNF-α. The combined detection of FLI1 with CRP, ESR, CCP, and RF demonstrated the highest efficacy in evaluating RA disease activity. The target genes most strongly associated with FLI1 were AGA, DCK, LRRC15, MAN2A1, and TES, all of which exhibited positive correlations with FLI1. The suppression of FLI1 expression led to a decreased expression of AGA, DCK, LRRC15, MAN2A1, and TES. Furthermore, the inhibition of FLI1 reduced the viability of RA synovial cells and promoted their apoptosis.FLI 1 is upregulated in RA and can promote inflammation, increase RA synovial cell viability, or inhibit synovial cell apoptosis. This finding suggests that FLI 1 and its target genes may serve as novel therapeutic targets in RA. The present findings integrate bioinformatics and experimental approaches to advance our current understanding of RA and open new avenues for targeted therapies.© 2025 Zhang et al.

Abstract: The existing drugs for ovarian cancer (OC) are unsatisfactory and thus new drug targets are urgently required. We conducted proteome-wide Mendelian randomization (MR) and colocalization analysis to pinpoint potential targets for OC.Data on protein quantitative trait loci (pQTL) for 734 plasma proteins were obtained from large genome-proteome-wide association studies. Genetic associations with OC were derived from the Ovarian Cancer Association Consortium, which included 25,509 cases and 40,941 controls. MR analysis was performed to evaluate the association between the proteins and the OC risk. Colocalization analysis was conducted to check whether the identified proteins and OC shared causal variants. In addition, the phenome-wide MR analysis was performed to clarify protein associations across the phenotype, and drug target databases were examined for target validation.Genetically predicted circulating levels of 44 proteins were associated with OC risk at Benjamini-Hochberg correction. Genetically predicted 17 proteins had evidence of the increased risk of OC (CLEC11A, MFAP2, TYMP, PDIA3, IL1R1, SPINK1, PLAU, DKK2, IL6ST, DLK1, LRRC15, CDON, ANGPTL1, SEMA4D, AKR1A1, TNFAIP6, and FCGR2B); 27 proteins decreased the risk of OC(SIGLEC9, RARRES1, SPINT3, TMEM132A, HAVCR2, CNTN2, TGFBI, GSTA1, HGFAC, TREML2, GRAMD1C, ASAH2, CPNE1, CCL25, MAPKAPK2, POFUT1, PREP, NTNG1, CA10, CACNA2D3, CA8, MAN1C1, MRC2, IL10RB, RBP4, GP5 and CALCOCO2). Bayesian colocalization demonstrated that GRAMD1C, RBP4, PLAU, PDIA3, MFAP2, POFUT1, MAN1C1 and DKK2 shared the same variant with OC. The phe-MR analyses assessed the side effects of these 44 identified proteins, and the drug target database offered information on both approved and investigational indications.This study provides proof of a causal relationship between genetically predicted 44 proteins associated with OC risk, which could serve as promising drug targets for OC.© 2025. The Author(s).

Abstract: Leucine-rich repeat containing 25 (LRRC25) is distinguishingly expressed in different tumor types, but the relationship with immune cell infiltration in gastric cancer stills unclear. We analyzed LRRC25 expression using pan-cancer data from The Cancer Genome Atlas and gene data from Gene Expression Omnibus. The clinical significance was further evaluated using gastric cancer tissues derived from clinical trials (no. NCT04208347).Through bioinformatics analysis of TCGA database and the UCSC Xena database, we found the correlation between LRRC15, gastric cancer, and immune cell infiltration. Further, multiplex immunohistochemistry/immunofluorescence (mIHC/IF), tissue microarray, and image acquisition and quantitative analysis confirmed our theory.It was discovered that LRRC25 was highly expressed in gastric cancer. Further analysis revealed that the expression of LRRC25 associated with gene sets implicated in immunity, including those in innate immunity, adaptive immunity, and chemokine signaling pathways. The result of (mIHC/IF) suggests a negative relevance between LRRC25 and response of anti-PD-1 treatment and reveals a trend of consistent change on LRRC25 + cells and CD16 expression. We also discovered that LRRC25 expression significantly associated with immune cell infiltration level. In particular, there is a relationship between LRRC25 and the phenotype and function of NK cells.High LRRC25 expression contributes to immunosuppressive microenvironment by influencing chemokine axis in gastric cancer. LRRC25 may serve as a clinically useful biomarker for predicting neoadjuvant immunotherapeutic response in patients with gastric cancer. LRRC25 can affect the phenotype and function of NK cells.© 2025. The Author(s).