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PubMed2026

Mast Cells Selectively Deliver Extracellular Vesicle-Encapsulated mRNA to Colorectal Cancer Cells.

Mast cells (MCs), a type of granulocytic immune cell, exert contrasting effects on tumorigenesis. The anti- or pro-tumorigenic activity of MCs depends on the cancer type, tumor microenvironment, and MC localization within the tumor. Consequently, their role remains controversial and poorly understood across multiple cancer types, including colorectal cancer (CRC). Most proposed mechanisms underlying MC activity in CRC have focused on MC secretion of biological factors. In this study, we demonstrated that MCs transfer extracellular vesicles containing mRNAs and proteins to CRC cells. This process occurs through a tightly regulated mechanism that requires direct cell-cell contact, calcium signaling, and integrin-mediated interactions. Such requirements resemble aspects of immunological synapses observed between lymphocytes and cancer cells. The novel mode of intercellular communication between MCs and cancer cells described here may help refine our understanding of MC functions in cancer biology.

Mast Cells↗

PubMed2025

Putative function and prognostic molecular marker of mast cells in colorectal cancer.

BACKGROUND: The increased demand for markers for colorectal cancer (CRC) highlights the importance of investigating immune cells involved in CRC progression. This study aims to dissect the mast cells in CRC, characterize the role of mast cells in CRC development, coordinate molecular communication between mast cells and malignant cells, and construct and validate a prognostic classification model based on mast cell markers. METHODS: Single-cell transcriptome data of CRC patients were extracted from GSE146771 for cell classification and annotation. The malignant cells were identified by copykat and the communication between mast cells and malignant cells was analyzed by CellChat. Least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression analysis of mast cell markers were performed in the TCGA-COAD cohort to construct a prognostic classification model. qRT-PCR was performed to detect the mRNA expression of the molecules in the classification model in P815 and MC-9 cells. The co-culture experiment of MC38 and P815 cells were performed in 12-well transwell dish. Wound healing assay and Transwell assay were performed to detect cell migration and invasion. RESULTS: 10,186 high-quality cells in GSE146771 were annotated to 9 cell types. Six markers in mast cells (HDC, GATA2, ASAH1, BTBD19, TIMP1, FAM110A) were selected to construct a classification model. The high-risk score defined showed high infiltration of immunosuppressive cells, including endothelial cells, CAFs, Tregs and high angiogenesis and epithelial-mesenchymal transition (EMT) activities. In the model, HDC were abnormally low expressed in P815 cells, while BTBD19, FAM110A, GATA2, ASAH1 and TIMP1 showed excessive expression in P815 cells. Knockdown of GATA2 in the co-culture system of P815 and MC38 cells blocked cell migration and invasion. CONCLUSION: This study identified the cell types within CRC, elaborated the cellular functions of mast cells in CRC development and their molecular communication to coordinate malignant cells, and highlighted the molecular components and biological features that constitute promising prognostic classification model.

Mast Cells↗

PubMed2024

Mast cells proliferate in the peri-hippocampal space during early development and modulate local and peripheral immune cells.

Brain development is a non-linear process of regionally specific epochs occurring during windows of sensitivity to endogenous and exogenous stimuli. We have identified an epoch in the neonatal rat brain defined by a transient population of peri-hippocampal mast cells (phMCs) that are abundant from birth through 2-weeks post-natal but absent thereafter. The phMCs are maintained by proliferation and harbor a unique transcriptome compared with mast cells residing in the skin, bone marrow, or other brain regions. Pharmacological activation of this population broadly increases blood-brain barrier permeability, recruits peripheral immune cells, and stunts local microglia proliferation. Examination of the post-mortem human brain demonstrated mast cells in the peri-hippocampal region of a newborn, but not an older infant, suggesting a similar developmental period exists in humans. Mast cells specifically, and early-life inflammation generally, have been linked to heightened risk for neurodevelopmental disorders, and these results demonstrate a plausible source of that risk.

Mast Cells↗

PubMed2026

Mast cell leukemia with complex genomic alterations in an elderly patient with prior hematologic and solid malignancies: a case report.

INTRODUCTION: Mast cell leukemia (MCL) is the rarest and most aggressive variant of systemic mastocytosis (approximately 1% of cases), with a median survival of under 2 years. Diagnosis requires ≥20% atypical mast cells in the marrow aspirate, and the disease frequently overlaps with myeloid neoplasms. CASE PRESENTATION: An 86-year-old man with paranasal sinus diffuse large B-cell lymphoma in remission since 2017 after R-CHOP and methotrexate, and prostate adenocarcinoma treated in 2019, presented with acute pancytopenia, presumed to represent lymphoma relapse. Serum tryptase exceeded 11 999 ng/mL; the aspirate showed 20% pleomorphic mast cells (CD117+, weak CD25, CD2-), confirming aleukemic MCL. Formal CMML criteria could not be confirmed due to the unavailability of monocyte differential data; however, the findings raised suspicion for an associated myeloid neoplasm, with SM with an associated hematological neoplasm remaining an alternative classification. Karyotyping was normal; next-generation sequencing revealed pathogenic variants in TP53, RB1, DAXX, ASXL1, TET2, and SRSF2, and a rare extracellular-domain KIT p.D419del. He declined inpatient midostaurin, deteriorated rapidly, and died 2 weeks later. CLINICAL DISCUSSION: This case illustrates a therapy-related MCL (plausible but unconfirmed given the non-leukemogenic profile of methotrexate and the focal nature of prostate stereotactic body radiation therapy) with a suspected associated myeloid neoplasm and complex pathogenic mutations. The KIT p.D419del extracellular domain variant is a rare non-D816V mutation; the canonical D816V was not detected on NGS, though the presence of a low-variant allele fraction D816V cannot be fully excluded due to assay sensitivity. Despite midostaurin, the disease remained aggressive. CONCLUSION: Persistent unexplained cytopenias warrant heightened suspicion of MCL, and comprehensive genomic profiling clarifies diagnosis, distinguishes overlapping myeloid disease, and informs prognosis in this aggressive, refractory neoplasm.

case report↗

PubMed2025

Well-differentiated systemic mastocytosis: Genetics, mast cell immunophenotypes, and KIT autophosphorylation.

BACKGROUND: Well-differentiated systemic mastocytosis (WDSM) is a rare myeloid neoplasm where the genetic etiology is often unknown. OBJECTIVE: We aimed to assess WDSM patients for novel KIT variants, mast cell (MC) aberrant immunophenotypes, and KIT autophosphorylation patterns. METHODS: Next-generation sequencing, MC immunophenotyping, and KIT autophosphorylation studies were performed. RESULTS: Among 454 SM patients, there were 432 with KIT p.D816V+ SM and 4 with KIT p.D816Y+ SM-notably, none of these patients had WDSM. Of the remaining patients, we identified 7 with WDSM (1.5%) and 2 relatives with mastocytosis in skin. Next-generation sequencing revealed that 6 of 9 subjects carried known or novel germline KIT variants corresponding to regions outside of codon 816. Three patients had germline KIT p.K509I; 2 had germline KIT p.A533D; 1 had two germline KIT variants p.F681L and p.M541L; and 3 had no KIT mutation. Intracellular expression of CD2 and CD25 and less robust expression of CD30 was observed in MCs from WDSM patients. By developing a novel transient transfection assay in 293T cells, we found that unlike KIT p.D816F/V/Y variants that exhibit nearly exclusive intracellular localization and strong ligand-independent autophosphorylation (class II), WDSM-associated KIT variants showed enhanced ligand-dependent autophosphorylation relative to wild type (class I). CONCLUSIONS: Our study doubles the number of KIT variants identified in WDSM patients. No KIT p.D816V+ SM patient had WDSM. Intracellular CD2 and CD25 expression was more robustly detected in MCs from WDSM patients compared to CD30.

Humans↗

PubMed2026

CXCL14 is a novel biomarker for mast cell infiltration in the melanoma tumor microenvironment.

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Letter↗

PubMed2024

Inhibiting the expression of spindle appendix cooled coil protein 1 can suppress tumor cell growth and metastasis and is associated with cancer immune cells in esophageal squamous cell carcinoma.

Inhibiting the expression of spindle appendix cooled coil protein 1 (SPDL1) can slow down disease progression and is related to poor prognosis in patients with esophageal cancer. However, the specific roles and molecular mechanisms of SPDL1 in esophageal squamous cell carcinoma (ESCC) have not been explored yet. The current study aimed to investigate the expression levels of SPDL1 in ESCC via transcriptome analysis using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Moreover, the biological roles, molecular mechanisms, and protein networks involved in SPDL1 were identified using machine learning and bioinformatics. The cell counting kit-8 assay, EdU staining, and transwell assay were used to investigate the effects of inhibiting SPDL1 expression on ESCC cell proliferation, migration, and invasion. Finally, the correlation between the SPDL1 expression and cancer immune infiltrating cells was evaluated by analyzing data from the TCGA database. Results showed that SPDL1 was overexpressed in the ESCC tissues. The SPDL1 expression was related to age in patients with ESCC. The SPDL1 co-expressed genes included those involved in cell division, cell cycle, DNA repair and replication, cell aging, and other processes. The high-risk scores of SPDL1-related long non-coding RNAs were significantly correlated with overall survival and cancer progression in patients with ESCC (P < 0.05). Inhibiting the SPDL1 expression was effective in suppressing the proliferation, migration, and invasion of ESCC TE-1 cells (P < 0.05). The overexpression of SPDL1 was positively correlated with the levels of Th2 and T-helper cells, and was negatively correlated with the levels of plasmacytoid dendritic cells and mast cells. In conclusion, SPDL1 was overexpressed in ESCC and was associated with immune cells. Further, inhibiting the SPDL1 expression could effectively slow down cancer cell growth and migration. SPDL1 is a promising biomarker for treating patients with ESCC.

Humans↗

PubMed2026

Integrated single-cell RNA sequencing and mendelian randomization analysis identifies causal immune-related driver genes in the heart failure inflammatory microenvironment.

BACKGROUND: Heart failure (HF) is a major global cause of cardiovascular death and disability. Chronic inflammation and immune dysregulation are critical in its development. The cardiac immune microenvironment, especially macrophages, drives HF progression, yet its molecular mechanisms and prognostic impact are not fully clear. This study aimed to identify causal immune-related driver genes in the HF inflammatory microenvironment. METHODS: We combined single-cell RNA sequencing (scRNA-seq) and Mendelian randomization (MR) to study how the inflammatory immune microenvironment affects HF risk. Using two public scRNA-seq datasets, we identified differentially expressed genes (DEGs) in HF heart tissues and selected 489 candidate genes. Causal relationships between these genes and HF were tested using expression quantitative trait loci (eQTL) data and HF genome-wide association study (GWAS) summary statistics. RESULTS: MR analysis showed that 65 genes were causally linked to HF risk. These genes were enriched in pathways related to cardiomyopathy, leukocyte migration, natural killer (NK) cell cytotoxicity, neutrophil extracellular traps, and NF-κB signaling. HF hearts displayed increased levels of macrophages, T cells, B cells, lymphoid cells, and mast cells, while neutrophils were reduced. CONCLUSIONS: Our integrated analysis reveals the central role of the cardiac inflammatory immune microenvironment in HF and identifies 65 key genes causally associated with HF susceptibility. These genes influence specific immune pathways and cell infiltration, shaping HF progression, and provide a basis for developing new biomarkers and immune-targeted therapies.

Heart failure (HF)↗

PubMed2026

Microplastics and nanoplastics-related genes signature predicts prognosis in pancreatic ductal adenocarcinoma and functional validation of interleukin 1 alpha.

BACKGROUND: Microplastics and nanoplastics (MNPs), as emerging environmental pollutants, have garnered significant attention from the global scientific community due to their potential threats to human health, particularly their association with the occurrence and development of cancer. The goal of our study is to create a predictive marker for pancreatic ductal adenocarcinoma (PAAD) based on MNPs-related genes, with the purposes of predicting survival outcomes and assessing the tumor immune microenvironment. METHODS: Using multi-cohort data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC), we assessed the association between MNPs and PAAD prognosis through the Xiantao Academic (https://www.xiantao.love/). The development of a prognostic signature was followed by an assessment of its significance through the Kaplan-Meier method, time-dependent receiver operating characteristic (ROC), and decision curve analysis (DCA). The validity of the risk model was confirmed through the ICGC and GSE71729 cohorts. The model was then assessed for levels of tumor immune infiltration. To explore MNPs-related genes expression characteristics within immune cells in PAAD, we performed single-cell RNA sequencing and spatial transcriptomics analysis through the Sparkle Platform (https://grswsci.top/). Finally, in vitro experiments were conducted to investigate the biological function of interleukin 1 alpha (IL1A). RESULTS: A four-gene signature comprising XDH, IL1A, KIF20A, and ASPM, based on MNPs, was developed to stratify PAAD patients into two distinct risk groups. The high-risk group showed a significantly poorer prognosis. A similar trend was verified in the external cohorts ICGC and GSE71729. The signature risk score affected immune cell infiltration in the PAAD microenvironment. The infiltration of B cells, CD8+ T cells, cytotoxic cells, immature dendritic cells (iDCs), mast cells, plasmacytoid dendritic cell (pDC), T cells, Tem cells, T follicular helper (TFH) cells, and T helper 17 (Th17) cells had a positive correlation with the low-risk group. In contrast, high-risk patients tended to have increased number of T helper (Th2) cells and higher expression of SIGLEC15, CD274, IGSF8. Knockdown of IL1A in PAAD cells inhibited their tumor proliferation ability in vitro. CONCLUSIONS: Using MNPs-related genes, we built a prognostic model for PAAD, revealing that patients with high-risk scores are likely to have a worse prognosis. This model is designed to develop personalized treatment strategies tailored to the specific needs of each patient, thereby improving clinical outcomes for PAAD patients. Furthermore, IL1A could be a promising therapeutic candidate for PAAD.

Microplastics↗

PubMed2026

Multi-omics Approaches to CCAAT/Enhancer-Binding Protein Beta in Oral Squamous Cell Carcinoma: Crosstalk Between Tumor Cells and Tumor-Associated Macrophages Driving Disease Progression.

BACKGROUND: CCAAT/Enhancer-Binding Protein Beta (CEBPB) is an important transcription factor that regulates tumor progression. However, the mechanism by which CEBPB regulates the progression of Oral Squamous Cell Carcinoma (OSCC) remains incompletely understood. Tumor progression depends on complex intercellular interactions within the tumor microenvironment. The purpose of this study was to investigate the role and epigenetic regulatory mechanisms of CEBPB in interactions between OSCC cells and tumor-infiltrating immune cells. METHODS: Bulk RNA-seq, ChIP-seq, and scRNA-seq data were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. The HOMER algorithm was employed to identify enhancers and predict the CEBPB-binding motif. Cell cluster analysis, functional enrichment, and intercellular interaction analysis were performed using the "Seurat" R package. H3K27ac enrichment at GAS6 enhancers was validated by ChIP-qPCR. Metastatic OSCC cells with CEBPB knockdown or GAS6 overexpression were established and co-cultured with THP-1 cells. IL-10 and IL-6 secretion from co-cultured THP-1 cells was detected via ELISA. Chemotaxis of OSCC cells toward THP-1 cells was assessed through a Transwell assay. RESULTS: CEBPB was upregulated in OSCC and correlated with poor prognosis. By integrating H3K27ac ChIP-seq and bulk RNA-seq data, 131 CEBPB-regulated enhancer-controlled genes were identified in lymph node metastatic OSCC cells. scRNA-seq analysis revealed eight major cell clusters in primary foci and lymph node metastases, including T/NK cells, malignant epithelial cells, B/plasma cells, macrophages, fibroblasts, dendritic cells, endothelial cells, and mast cells, with the malignant epithelial cells stratified into distinct sub-clusters. CEBPB expression was elevated in malignant epithelial cells of lymph node metastases compared to primary foci. Furthermore, 15 pairs of enhanced ligand-receptor interactions were identified in lymph node metastases relative to primary foci. GAS6 was a CEBPB-regulated enhancer-controlled gene, primarily mediating interactions between malignant cells and macrophages. CEBPB knockdown in metastatic OSCC cells significantly impaired their chemotaxis toward cocultured THP-1 cells, and downregulated IL-10/IL-6 secretion and CD206 expression in cocultured THP-1 cells. Conversely, GAS6 overexpression reversed these inhibitory effects. CONCLUSION: CEBPB activated GAS6 transcription in metastatic OSCC cells. The CEBPB/ GAS6 axis in metastatic OSCC cells enhanced their chemotaxis toward macrophages and promoted the M2 polarization of macrophages, thereby facilitating the establishment of an immunosuppressive microenvironment.

Humans↗

PubMed2026

ARHGAP22 as a Potential Prognostic Biomarker in Clear Cell Renal Cell Carcinoma: Insights into Tumor Immunity and Co-Expression Networks.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and is characterized by substantial clinical heterogeneity, highlighting the need for reliable prognostic biomarkers. This study evaluated the expression pattern, prognostic relevance, and immune-related associations of ARHGAP22 in ccRCC using transcriptomic and clinical data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) cohort, together with external validation data and protein-expression information from the Human Protein Atlas (HPA). ARHGAP22 expression was compared between tumor and adjacent normal tissues, and its associations with overall survival, clinicopathological characteristics, tumor microenvironment scores, and estimated immune-cell fractions were assessed. Co-expression and functional-enrichment analyses were also performed to characterize potential biological associations. ARHGAP22 was significantly upregulated in ccRCC tissues at the transcriptomic level, with corresponding differences observed in immunohistochemical images. High ARHGAP22 expression was associated with shorter overall survival, advanced clinicopathological features, and higher ImmuneScore, StromalScore, and ESTIMATEScore values. CIBERSORT-based analysis showed that the high-expression group had higher estimated fractions of M2 macrophages and regulatory T cells and lower estimated fractions of naïve B cells, resting mast cells, and activated dendritic cells after false discovery rate correction. Functional-enrichment analyses linked ARHGAP22-associated genes to immune-related processes, cell migration, and chemokine- and cytokine-mediated signaling pathways. These findings suggest that ARHGAP22 may represent a potential prognostic and immune-related biomarker in ccRCC, although further independent clinical and experimental validation is required.

Humans↗

PubMed2026

Integrated Multi-omics Profiling of 2,4-dinitrochlorobenzene (DNCB)-induced Atopic Dermatitis in Mice Reveals a Coordinated Network of Barrier Dysfunction, Immune Activation, and Metabolic Reprogramming.

Atopic dermatitis (AD) is caused by a combination of epidermal barrier defect and immune imbalance. However, the molecular networks between these structural abnormalities and metabolic variations are unclear. This study aim of this research was to examine the concurrent molecular alterations in skin barrier damage and metabolic disorders in an AD-like mouse model by a multi-omics strategy. A 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model was established and the skin tissues were examined through the combination of transcriptomic, quantitative proteomic, and metabolomic analyses. Cross-omics correlation and network analyses were performed to identify consistently abnormal molecular pathways and crucial regulatory molecules. DNCB treatment caused severe epidermal hyperplasia, and prominent infiltration of CD3⁺ T cells, F4/80⁺ macrophages, and mast cells. Transcriptomic and proteomic analysis indicated significant disruption in keratinocyte differentiation, extracellular matrix organization, and cornified envelope formation pathways. Combined analysis detected 171 molecules which were simultaneously altered at both mRNA and protein levels, and network analysis identified FLG2 and KRT6B as central barrier-related molecules. Pathway enrichment analysis consistently showed the participation of AMPK and PPAR signaling pathways. Metabolomic analysis also revealed coordinated changes in lipid and amino acid metabolism which were closely associated with cornified envelope-associated genes and collagen-modifying enzymes. These findings indicate a close relationship between barrier, immune and metabolic regulation in DNCB-induced dermatitis and provide a multi-omics resource for future mechanistic studies of atopic skin inflammation.

Animals↗

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

Sex-Dependent Microbial and Host Profiles Following Fecal Microbiota and Bifidobacterium longum Treatment in Stress-Induced Gut Dysbiosis.

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder influenced by stress, microbial dysbiosis, and immune activation. Microbiota-directed therapies, including fecal microbiota transplantation and probiotics, show promise, but their sex-specific effects remain unclear. We compared the therapeutic effects of lyophilized fecal microbiota (LFM) with Bifidobacterium longum BBH016 in male and female Wistar rats subjected to repeated water avoidance stress. METHODS: Fecal pellet output (FPO), colonic mast cell infiltration, and fecal short-chain fatty acids were measured. Gut microbial composition and function were analyzed by 16S rRNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway prediction. RESULTS: Both interventions significantly reduced FPO and mast cell infiltration in males but had less pronounced effects in females. Microbiota analyses revealed sex-dependent responses, with distinct microbial trajectories in each treatment group. Using linear discriminant analysis effect size, we identified seven key taxa with treatment- or sex-specific enrichment. Alistipes onderdonkii and Bacteroides uniformis consistently increased in both LFM- and B. longum-treated groups, regardless of sex. Bacteroides finegoldii and Barnesiella intestinihominis were specifically enriched in the LFM group. In males, Blautia faecis and Fusicatenibacter saccharivorans were enriched following the interventions, whereas Parabacteroides goldsteinii appeared exclusively in stressed males. Functional predictions revealed the enrichment of estrogen signaling and bile acid pathways in males and the attenuation of proinflammatory pathways in females following LFM. Correlations between microbial taxa and host outcomes were predominantly observed in male rats. CONCLUSIONS: These findings highlight sex-specific microbial and host responses to microbiota-targeted therapies in a stress-induced IBS model, emphasizing sex as a biological variable in designing personalized microbiome-based treatments.

Animals↗

PubMed2026

Tumor microbial burden drives immune responses through regulation of Interferon signaling.

Tumor microbes are increasingly recognized for modulating tumor behavior and therapy responses. Intratumoral microbial burden (ITMB) analysis across cancers revealed regulation of immune pathways, and activated mast cells, mostly in colorectal (CRC) and gastric (STAD) cancers. High ITMB CRC leads to interferon regulation and is associated with improved outcomes in advanced disease. Single-cell sequencing revealed induction of interferon-related genes (IRGs) within microbes-containing human CRC. GI-luminal mismatch repair deficiency (MMRd) tumors had higher ITMB than proficient tumors (MMRp). In a rectal MMRd cohort with 100% remission after immune checkpoint blockade (ICB), tumor microbes and microbes-containing mast cells increased. In ICB-sensitive syngeneic murine MMRd tumor models, local tumor microbial depletion, impaired ICB efficacy while downregulating IFN signaling. Forced upregulation of IRGs in ADAR1-deficient cancer cells restored immunotherapy responses during microbial ablation. These data highlight dynamic interplay between ITMB, host defense, and immunogenicity which seems key to determine therapy responses.

Journal Article↗

PubMed2024

Identification and analysis of key genes related to efferocytosis in colorectal cancer.

UNLABELLED: The impact of efferocytosis-related genes (ERGs) on the diagnosis of colorectal cancer (CRC) remains unclear. In this study, efferocytosis-associated biomarkers for the diagnosis of CRC were identified by integrating data from transcriptome sequencing and public databases. Finally, the expression of biomarkers was validated by real-time quantitative polymerase chain reaction (RT-qPCR). Our study may provide a reference for CRC diagnosis. BACKGROUND: It has been shown that some efferocytosis related genes (ERGs) are associated with the development of cancer. However, it is still uncertain how ERGs may influence the diagnosis of colorectal cancer (CRC). METHODS: In our study, the CRC cohorts were gained from transcriptome sequencing and the gene expression omnibus (GEO) database (GSE71187). Efferocytosis related biomarkers with diagnostic utility for CRC were identified through combining differentially expressed analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. Then, infiltration abundance of immune cells between CRC and control was evaluated. The regulatory networks (including mRNA-miRNA-lncRNA and miRNA/transcription factors (TF)-mRNA networks) were created. Finally, the expression of biomarkers was validated via real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: There were 3 biomarkers (ELMO3, P2RY12, and PDK4) related diagnosis for CRC patients gained. ELMO3 was highly expressed in CRC group, while P2RY12 and PDK4 was lowly expressed. Besides, the infiltrating abundance of 3 immune cells between CRC and control groups was significantly differential, namely activated CD4 memory T cells, macrophages M0, and resting mast cells. We then constructed a mRNA-miRNA-lncRNA network containing 3 mRNAs, 33 miRNAs, and 22 lncRNAs, and a miRNA/TF-mRNA network including 3 mRNAs, 33 miRNAs, and 7 TFs. Additionally, RT-qPCR results revealed that the expression trends of all biomarkers were consistent with the transcriptome sequencing data and GSE71187. CONCLUSION: Taken together, this study provides three efferocytosis related biomarkers (ELMO3, P2RY12, and PDK4) for diagnosis of CRC, providing a scientific reference for further studies of CRC.

Humans↗

PubMed2026

Targeted variant analysis of feline mediastinal lymphoma using MassARRAY and clinical associations.

Lymphoma is the most commonly diagnosed cancer in cats. This study used the Agena MassARRAY to genotype 40 variants across 17 genes in feline mediastinal lymphoma. These variants have previously been identified in tumors, including T- and B-cell lymphomas, acute and chronic lymphocytic leukemias, and mast cell tumors, in humans, dogs, and cats, using various methods. They were selected based on high prevalence reported in prior oncology studies, potential relevance to targeted therapy, and suitability for multiplex PCR amplification. Pleural fluid samples were collected from 76 cats with mediastinal lymphoma, including 69 domestic shorthairs, two Persians, two Siamese, two Wichienmaat, and one Scottish Fold. The most prevalent variants were found in the BCL2, KIT, STAT3, and ZEB1 genes. Specifically, BCL2 c.83275986G > A and c.83275992G > T were present in 71.1% and 57.9%, respectively. In cats with variant-positive in KIT c.163965724C > CT significantly reduced (11 days) compared to wild-type cats (94 days) (p < 0.001). In cats with variant-positive in STAT3 c.42942437C > CA, resulted in shorter median survival compared to wild-type cats (18 days vs. 77 days, p = 0.006). The findings suggest that the variant panel could be useful for the genomic landscape of feline mediastinal lymphoma and warrant further validation.

Animals↗

PubMed2025

Impact of stromal maturity and proportion on prognosis and immune landscape in colorectal cancer.

BACKGROUND: Tumour microenvironment and cancer cells have constant interaction affecting cancer progression. Tumour-stroma ratio (TSR) in the tumour centre and desmoplastic reaction (DR) classification at the invasive margin are prognostic factors based on stroma evaluation on H&E slides. However, their combined value and immunological associations remain poorly defined. This study examines the prognostic and immunological value of TSR, DR, and their combination in two large colorectal cancer cohorts. METHODS: Two colorectal cancer cohorts (N = 1,876) were analyzed. We introduced a three-tiered Stromal Maturity and Proportion Score (SMAPS) based on the presence of high (>50%) TSR and myxoid stroma (immature DR classification). Alcian blue staining was used to further quantify myxoid stroma. Multiplex immunohistochemistry combined with digital image analyses, was utilized to study immune cell densities associated with SMAPS, TSR, DR, and Alcian blue intensity. RESULTS: In the study cohort (N = 1,100), SMAPS was a stronger predictor of cancer-specific mortality [HR for high (vs. low) SMAPS 2.01 (95% CI 1.47-2.75), p < 0.0001] compared to TSR [HR for stroma-high (vs. stroma-low) 1.49 (95% CI 1.15-1.93), p = 0.003] and DR classification [HR for immature (vs. mature) 1.84 (95% CI 1.39-2.45), p < 0.0001]. High SMAPS, stroma-high TSR, and immature DR correlated with lower densities of CD3+ T cells, B cells, M1-like macrophages, CD66B+ granulocytes, and mast cells. Alcian blue staining was associated with immature DR and corresponding immune cells. The validation cohort (N = 776) confirmed the association of SMAPS with survival and T cell densities. CONCLUSIONS: TSR and DR are independent prognostic factors for cancer-specific survival. SMAPS is a promising prognostic tool that integrates stromal maturity at the invasive margin and stromal proportion in the tumour centre. SMAPS has stronger prognostic value compared to TSR and DR classifications alone. A high stromal proportion and myxoid content are associated with an immunosuppressive microenvironment characterized by lower densities of antitumourigenic immune cells.

Humans↗