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PubMed2026

Profiling Dectin-2-Positive Tumor-Associated Macrophages Across Human Cancers by Immunohistochemistry.

PURPOSE: To characterize the prevalence and distribution of Dectin-2-positive macrophages across human tumors and develop a research immunohistochemistry (IHC) assay to assess Dectin-2 in cancer tissues. MATERIALS AND METHODS: C-type lectin domain family 6 member A (CLEC6A), the gene encoding Dectin-2, was evaluated across 38 tumor types using The Cancer Genome Atlas. A fit-for-purpose Dectin-2 IHC assay was developed using a monoclonal antibody selected from screening 11 anti-Dectin-2 antibodies. Assay performance was supported by Dectin-2-expressing and parental cell line controls, macrophage-associated staining patterns, and comparison with an orthogonal CLEC6A in situ hybridization method using RNAscope. Dectin-2 expression was assessed in tissue microarrays (n = 553 samples) across 6 cancer types and whole tissue sections (n = 137) across 7 cancer types. RESULTS: The Cancer Genome Atlas analysis identified enriched CLEC6A expression in several tumor types, including non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), and subsets of head and neck cancer (HNC) and colorectal cancer (CRC). By IHC, Dectin-2-positive macrophages were detected across tumor types, with notable heterogeneity within and across cancer types. In tissue microarrays, NSCLC showed the highest frequency of Dectin-2-positive macrophage infiltration, with 38% of cases with staining ≥1% of tumor area. Whole tissue section analysis confirmed and expanded these findings, with ≥50% of NSCLC, melanoma, HNC, TNBC, and CRC samples showing Dectin-2-positive macrophages in ≥1% tumor area. CONCLUSIONS: Dectin-2 expression was observed in subsets of tumor-associated macrophages across multiple human cancers, with relatively enriched expression in NSCLC, melanoma, HNC, TNBC, and CRC. To our knowledge, this study represents the first broad protein-level characterization of Dectin-2 across multiple human tumor types, identifies cancers with relatively enriched Dectin-2-positive macrophage infiltration, and provides a foundation for future translational studies of Dectin-2-targeted therapies.

Humans↗

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

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↗

PubMed2026

Temporal Transcriptomic Profiling of NMBA-Induced Rat Esophageal Squamous Carcinogenesis Identifies Early Inflammatory Activation and Late NRF2-Associated Oxidative-Stress Remodeling.

Temporal molecular events during early esophageal squamous carcinogenesis remain incompletely defined, in part because human precursor tissues are difficult to obtain sequentially. We used the N-nitrosomethylbenzylamine (NMBA)-induced rat model to characterize stage-associated transcriptional programs during esophageal squamous carcinogenesis. Vehicle-control reference esophageal tissues and NMBA-treated esophageal tissues, collected at weeks 6 and 29, were profiled using Affymetrix Rat Genome 230 2.0 arrays, followed by pathway analysis and qRT-PCR validation of selected genes. Relative to vehicle-control reference tissues, 173 genes were differentially expressed at week 6, whereas 1628 genes were differentially expressed at week 29, indicating marked expansion of transcriptional dysregulation during carcinogenic progression. Sixteen genes were differentially expressed only at week 6, while 157 genes were altered at both time points. Pathway analysis suggested that inflammatory and immunologic processes were prominent during the early response to NMBA exposure, whereas late-stage carcinogenesis was characterized by NRF2-associated oxidative-stress response and dysregulation of multiple glutathione S-transferase family members. A subset of progression-associated genes, including Defb4, Gsta2, Sbsn, Spink5, Plcd4, Hbb, and Hba-a2, showed increasing dysregulation from week 6 to week 29. These findings define temporally distinct molecular programs in NMBA-induced esophageal squamous carcinogenesis and provide a framework for prioritizing candidate pathways and genes relevant to esophageal cancer prevention, early detection, and progression biology.

Animals↗

PubMed2026

Integrative transcriptomic, spatial and functional-genomic analysis identifies a UFMylation-related vascular-stromal program and prioritizes WWTR1 in glioblastoma.

Glioblastoma (GBM) contains spatially organized stress-adaptive and vascular niches. Because transcript abundance does not measure UFM1 conjugation, we asked whether a UFMylation-related transcriptional axis identifies a reproducible tissue program and alters candidate prioritization. In 518 unique primary TCGA-GBM tumors profiled on the Affymetrix HT Human Genome U133A array, weighted gene co-expression network analysis of 8,000 variable genes yielded 12 modules. The 278-gene green module ranked first across nine prespecified traits (mean |r|=0.637). Direct overlap comprised 1/3 measurable UFMylation-core, 5/19 ER-stress/UPR, and 2/15 proteostasis genes; after excluding overlapping genes, correlations with the green eigengene remained significant (r = 0.373, 0.831, 0.639, and 0.699 for UFMylation-core, ER-stress/UPR, proteostasis, and composite scores, respectively). The green score was associated with overall survival per standard-deviation increase (HR 1.17, 95% CI 1.07-1.28), although clinical adjustment attenuated the estimate. In a 10-sample single-cell dataset, sample-level scores were higher in pericytes and endothelial cells than in malignant cells. Donor-aware IvyGAP analysis supported regional organization, whereas one Visium section showed stronger concordance with ER-stress/UPR and mesenchymal scores than with the UFMylation-core score. CellChat indicated pathway-selective rather than global remodeling of inferred vascular communication. Layer ablation moved WWTR1 from rank 48 using WGCNA alone to rank 4 overall and rank 1 among non-common-essential genes after cross-platform integration. These findings define an ER-stress/mesenchymal-weighted, UFMylation-related vascular-stromal transcriptional association and nominate WWTR1 for experimental testing.

Humans↗

PubMed2026

CpGene: a web application for epigenetic signature identification from DNA methylation arrays.

MOTIVATION: DNA methylation (DNAme) is the best studied epigenetic mechanism that plays pivotal role in tissue differentiation and epigenetic disruption has been correlated to diverse disease types (e.g. cancer, metabolic disorders). While various DNAme array platforms have been discovered, data analysis remains a challenging task which often requires in-depth bioinformatic expertise. Here, we developed a user-friendly web-based application for data analysis and visualization that accommodates users ranging from early-career basic/translational researchers to experienced bioinformaticians. RESULTS: CpGene is a web application for analyzing DNA methylation array data. It supports Illumina 450K, EPIC, and EPICv2 methylation array platforms and processes .idat files with integrated preprocessing, normalization, and quality control. Biomarker discovery is available through either classic differential methylation point analysis or machine learning-based feature selection as well as gene enrichment analysis. Results are summarized with clear visualizations, to aid interpretation. By combining these functions in a unified interface, CpGene streamlines methylation analysis and helps identify CpG sites and genes with biological and clinical relevance. AVAILABILITY AND IMPLEMENTATION: CpGene is openly accessible as a web service through http://cpgene.duckdns.org:8001/ and it's source code is available on https://github.com/kostaslazaros/cpgenene.

DNA Methylation↗

PubMed1978

[Overacidified tissue and microcirculation (author's transl)].

A discussion of physiological fundamentals with respect to the inhibition of blood microcirculation in (tumor) tissue at reduced pH values around 6.0 is followed by a report on principles, design and results obtained with a light probe array which permits to determine in vivo reference values of the relative intensity of microcirulation in both normal and tumor tissues under various conditions. An analysis of the discussed records has shown that--as compared to a value of 80-66% without glucose infusion--the relative mean intensity of microcirculation in tumor tissue drops to approximately 8-4% about 300 min after the onset of glucose infusion under CMT administration at 37 degrees C. By adding the CMT step of hyperthermy, the relative mean intensity of microcirculation--compared to normal tissue at 37 degrees C--will further drop below 1%. With such a decline of microcirculation--and an adequate duration of, say, 8 hours--local hyperthermy at 41-42 degrees C is likely to cause a very pronounced damaging action on tumor tissue because the then noticeably reduced substrate offer proves to be insufficient to ensure the structure-maintaining metabolic rate of cancer cells.

Animals↗

PubMed2025

Methylation Signatures Identify Two Distinct Clusters of Uterine Leiomyosarcoma With Unique Histologic and Clinical Behaviors.

Uterine leiomyosarcoma (uLMS) is a rare and deadly gynecologic malignancy. uLMS is histologically heterogeneous and presents with a wide spectrum of tumor differentiation, with a broad range of genomic DNA instability, which can make the diagnosis and prognosis of uLMS challenging. Methylation has emerged as a useful molecular tool in tumor classification and diagnosis in certain neoplasms. We initiated this study to investigate the role of global methylation in the differential diagnosis of uLMS from its mimics in correlation with pathologic characteristics and clinical outcomes. In this study, we performed array-based global methylation profiling analysis in a total of 71 uLMS and compared the methylation signatures of uLMS with several other uterine mesenchymal tumors and soft tissue leiomyosarcoma. We found that uLMS demonstrated distinct methylation patterns differing from all other tumor types. Notably, methylation profiling defines 2 distinct subgroups of uLMS with differing copy number alterations, resulting in unique histologic and clinical behaviors, further emphasized by differences in methylation pathway analysis. This study is the first to report methylation profiling as a useful diagnostic tool in differentiating uLMS from mimics and defines 2 subtypes of uLMS based on methylation signatures.

Humans↗

PubMed2004

Function-informed transcriptome analysis of Drosophila renal tubule.

BACKGROUND: Comprehensive, tissue-specific, microarray analysis is a potent tool for the identification of tightly defined expression patterns that might be missed in whole-organism scans. We applied such an analysis to Drosophila melanogaster Malpighian (renal) tubule, a defined differentiated tissue. RESULTS: The transcriptome of the D. melanogaster Malpighian tubule is highly reproducible and significantly different from that obtained from whole-organism arrays. More than 200 genes are more than 10-fold enriched and over 1,000 are significantly enriched. Of the top 200 genes, only 18 have previously been named, and only 45% have even estimates of function. In addition, 30 transcription factors, not previously implicated in tubule development, are shown to be enriched in adult tubule, and their expression patterns respect precisely the domains and cell types previously identified by enhancer trapping. Of Drosophila genes with close human disease homologs, 50 are enriched threefold or more, and eight enriched 10-fold or more, in tubule. Intriguingly, several of these diseases have human renal phenotypes, implying close conservation of renal function across 400 million years of divergent evolution. CONCLUSIONS: From those genes that are identifiable, a radically new view of the function of the tubule, emphasizing solute transport rather than fluid secretion, can be obtained. The results illustrate the phenotype gap: historically, the effort expended on a model organism has tended to concentrate on a relatively small set of processes, rather than on the spread of genes in the genome.

Animals↗

PubMed2026

GWAS Meta-analysis Identifies Novel Associated Loci and Points to Causal Tissues in Central Serous Chorioretinopathy.

OBJECTIVE: To define CSC genetic architecture and identify implicated ocular tissues, cell types, genes, and circulating proteins. DATA SOURCES: Genome-wide data were assembled from FinnGen, All of Us, Mass General Brigham Biobank, Million Veteran Program, and a Dutch chronic CSC cohort. Serum protein quantitative trait loci, human single-cell ocular atlases, and UK Biobank macular optical coherence tomography (OCT) imaging were used for downstream analyses. STUDY SELECTION: Five European-ancestry cohorts with genome-wide data and cohort-specific CSC case-control definitions were included, comprising 2,584 cases and 1,044,455 controls. Variants present in at least 2 cohorts were meta-analyzed. DATA EXTRACTION AND SYNTHESIS: Cohort-level GWASs were adjusted for age, age squared, sex, genotyping array or batch, and 10 genetic principal components, then combined using fixed-effects inverse-variance meta-analysis. Post-GWAS analyses included gene prioritization, colocalization, Mendelian randomization, single-cell disease-relevance scoring, and testing of a CSC genetic risk score in UK Biobank OCT images. MAIN OUTCOMES AND MEASURES: Genome-wide significant CSC loci, effector genes and proteins, tissue and cell-type enrichment, and CSC-relevant OCT abnormalities. RESULTS: Across 11,068,938 variants, 10 loci reached genome-wide significance (P < 5 × 10-8), including 3 novel loci near TGFB1, LINC00551, and LOC105375630 and 7 replicated loci near CFH, CD46, NOTCH4, PREX1, PTPRB, GATA5, and TNFRSF10A. Integrative analyses prioritized 10 candidate effector genes. Colocalization and Mendelian randomization implicated circulating TNFRSF10A, TGFB1, and CASP10 levels. Single-cell analyses localized genetic risk to sclera (P = 2.0 × 10-4) and vascular endothelial cells (P = 4.0 × 10-4), with fibroblast enrichment. In UK Biobank, OCT abnormalities were more frequent in the top vs bottom 1% of CSC genetic risk (18 of 109 [16.5%] vs 8 of 134 [6.0%]; odds ratio, 4.05; 95% CI, 1.65-10.87; P = .002). CONCLUSIONS AND RELEVANCE: In this GWAS meta-analysis, CSC susceptibility localized predominantly to scleral and vascular biology rather than primary retinal pigment epithelial dysfunction. These findings support CSC as a sclerovascular disorder and nominate complement regulation, endothelial signaling, and extracellular matrix pathways for future study.

Journal Article↗

PubMed2024

PANAMA-enabled high-sensitivity dual nanoflow LC-MS metabolomics and proteomics analysis.

High-sensitivity nanoflow liquid chromatography (nLC) is seldom employed in untargeted metabolomics because current sample preparation techniques are inefficient at preventing nanocapillary column performance degradation. Here, we describe an nLC-based tandem mass spectrometry workflow that enables seamless joint analysis and integration of metabolomics (including lipidomics) and proteomics from the same samples without instrument duplication. This workflow is based on a robust solid-phase micro-extraction step for routine sample cleanup and bioactive molecule enrichment. Our method, termed proteomic and nanoflow metabolomic analysis (PANAMA), improves compound resolution and detection sensitivity without compromising the depth of coverage as compared with existing widely used analytical procedures. Notably, PANAMA can be applied to a broad array of specimens, including biofluids, cell lines, and tissue samples. It generates high-quality, information-rich metabolite-protein datasets while bypassing the need for specialized instrumentation.

Proteomics↗

PubMed2026

Beckwith-Wiedemann spectrum exhibiting a 46,XY karyotype caused by genome-wide paternal uniparental heterodisomy: a case report.

BACKGROUNDS: Patients with genome-wide paternal uniparental disomy (GWpUPD) usually exhibit clinical features of Beckwith-Wiedemann syndrome (BWS) and a 46,XX karyotype, with all chromosomes showing isodisomy. To date, male patients with GWpUPD and a complete 46,XY karyotype, specifically involving heterodisomy, have not been described. RESULTS: We report a male infant exhibiting classical BWS clinical features. DNA methylation analyses showed paternal-specific methylation across multiple imprinted loci, suggesting GWpUPD. Genetic analysis of autosomes and sex chromosomes indicated two distinct paternal genomes in peripheral blood leukocytes, whereas a normal biparental genome was detected in other tissues under chimeric conditions. These findings indicated that the patient had genome-wide paternal uniparental heterodisomy (GWpUPhD). The SNP array revealed the presence of one copy of the X chromosome and one copy of the Y chromosome, the patient is a chimera composed of 46,XY biparental cells (with maternal X) and 46,XY GWpUPhD cells (with paternal X). CONCLUSIONS: This is the first report of a male patient with a GWpUPhD chimera. We propose a potential mechanism of GWpUPhD formation. Our findings expand the molecular spectrum of GWpUPD and provide valuable insights into its pathogenesis in chimeric conditions. Furthermore, the potential for clinical manifestations unique to 46,XY heterodisomy warrants careful long-term follow-up.

Humans↗

PubMed2026

Integrative Analysis Uncover the Effects and Multi-Omics Features of Thigh Muscle Fat Infiltration.

The health impacts and underlying biological pathways of thigh muscle fat infiltration (TMFI) remain incompletely understood. In this study, we analyzed TMFI measured by magnetic resonance imaging in 55,120 UK Biobank participants and found that higher TMFI was significantly associated with all-cause mortality as well as with all major system-specific diseases examined (p values ranged from 2.50 × 10-88 to 9.97 × 10-04). TMFI also mediated the effects of lifestyle factors on health-related outcomes, with mediation proportions ranging from 6.7% to 71.7%. A genome-wide association study (GWAS) identified 79 lead single nucleotide polymorphisms (SNPs) linked to TMFI, and the polygenic risk score for TMFI was significantly associated with mortality and all incident diseases across examined organ systems in an independent subset of UK Biobank participants of European ancestry who were not included in the TMFI GWAS (n = 362,286, all p < 0.05). Gene-drug interactions identified multiple drugs that could potentially modulate TMFI. Analysis of single-cell transcriptomic data indicated that myogenic cells were strongly linked to TMFI (p = 7.08 × 10-08). Summary-data-based Mendelian randomization and Transcriptome-Wide Association Study analyses revealed numerous genes whose expression in specific tissues was associated with TMFI. Proteomic and metabolomic profiling uncovered a broad array of circulating biomarkers associated with TMFI, many of which mediated the effects of modifiable factors and genetic risk on TMFI. Overall, our results highlight the biological relevance of TMFI to human health and provide insights into the multi-omics mechanisms underlying TMFI, identifying potential targets for interventions.

Humans↗

PubMed2026

DNA Methylation and Proteomic Profiling of Postmortem Brain Tissue Reveals Epigenetic Dysregulation and Neuroinflammatory in Fragile X-associated Tremor/Ataxia Syndrome (FXTAS).

BACKGROUND: Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by FMR1 premutation CGG repeat expansions (55-200 repeats). The epigenetic landscape of the FXTAS brain remains uncharacterized. We performed genome-wide DNA methylation profiling of postmortem prefrontal cortex tissue to identify differentially methylated positions (DMPs) and candidate genes, and sought protein-level support for a neuroinflammatory signal. METHODS: DNA methylation was profiled in postmortem prefrontal cortex (Brodmann area 9) from 27 male FXTAS cases and 29 male controls using the Illumina MethylationEPIC array (EPICv1 and EPICv2 platforms), merging 721,802 common probes. Surrogate variable analysis (SVA) controlled for confounders. DMPs were defined by |Δβ| > 0.10 and FDR < 0.05; exploratory Reactome 2024 pathway analysis was performed on the DMP-associated gene list. Targeted proteomic profiling was performed in the same brain region using the Olink (proximity extension assay) Inflammation panel in 9 FXTAS cases and 12 controls, with SVA-adjusted differential abundance analysis, and concordance assessment against a prior mass spectrometry dataset. RESULTS: We identified 108 significant cg-type DMPs mapping to 80 genes (50 hypermethylated, 58 hypomethylated in FXTAS). The strongest signal was CYP2E1 (7 concordant hypomethylated DMPs, mean Δβ = -0.143), an oxidative stress gene also implicated in Parkinson's disease. FTCD, a one-carbon cycle enzyme, carried 5 hypermethylated DMPs (mean Δβ = +0.210). A cluster of DMP-associated genes with established roles in innate immune and NF-κB signaling, TRAF3 (the single most significant DMP among the inflammation genes, hypermethylated), BATF, RCOR1, and MSI2; they pointed toward neuroinflammatory dysregulation. Additional genes included LINGO1 (myelination inhibitor), SYT3 (synaptic vesicle), and SLC39A4 (zinc transporter). Exploratory Reactome enrichment using the DMP-associated gene set nominated themes including neuroinflammation resolution, axonal growth inhibition, zinc homeostasis, and CYP2E1 metabolism at nominal significance (p<0.05); however, the gene-to-pathway mapping rate was low and no pathway survived correction for multiple testing. Olink proteomic analysis independently identified 60 significantly altered inflammation proteins (59 downregulated), including CXCL8, CXCL10, IL6, IL15, IL18, TLR3, IRAK1/4, and complement C1QA, which were directionally concordant with prior mass spectrometry data. CONCLUSIONS: This integrated study reveals a genome-wide epigenetic signature in the FXTAS prefrontal cortex implicating oxidative stress, myelination failure, zinc dysregulation, one-carbon cycle disruption, and most notably a coordinated set of epigenetically altered genes governing innate immune and NF-κB signaling. Convergence of TRAF3 hypermethylation with independent downregulation of TLR3 and NF-κB-pathway proteins at the protein level supports a coherent, cross-platform model of dysregulated neuroinflammatory signaling in FXTAS, identified here through individual gene- and protein-level convergence rather than formal pathway enrichment. FTCD hypermethylation proposes a self-reinforcing epigenetic loop via SAM depletion. These multi-omic findings establish FXTAS as a disorder of pervasive epigenetic reprogramming and nominate candidate genes for future mechanistic and therapeutic investigation.

CYP2E1↗

PubMed2026

Identification and characterization of G protein-coupled receptors in the nocturnal halictid bee Megalopta genalis.

G protein-coupled receptors (GPCRs) are one of the largest families of membrane proteins in insects, regulating vision, neural signal transduction, and various physiological behaviors. Megalopta genalis exhibits a unique facultatively eusocial lifestyle and possesses adaptations for nocturnal activity; however, its GPCR family has not yet been systematically characterized. In this study, we performed genome-wide identification, phylogenetic analysis, and expression profiling of GPCRs in M. genalis by integrating genomic annotation and transcriptomic analysis. The results showed that a total of 99 GPCRs were identified in the genome of M. genalis, which were classified into four major families. Here, we show that M. genalis has undergone lineage-specific GPCR repertoire remodeling, marked by the expansion of novel orphan receptors and the systematic loss of multiple receptor subtypes, such as the neuropeptide receptors MIP-R and NPFR. Moreover, opsins have formed a diverse array of combinations and non-GPCR odorant receptors have undergone significant expansion via tandem duplication. Together, these features may represent part of the molecular repertoire associated with the adaptation of M. genalis to a nocturnal lifestyle. Furthermore, transcriptomic analysis revealed distinct spatiotemporal expression divergence within each of the Mth/Mthl and Fz GPCR families, suggesting functional specialization across development and adult tissues. This study provides the first systematic identification and initial functional characterization of GPCRs in M. genalis, revealing an evolutionary pattern characterized by the coexistence of contraction and expansion within the GPCR family. These findings lay a foundation for further studies aimed at elucidating the roles of these GPCRs in regulating M. genalis physiology and behavior.

Animals↗

PubMed2025

Transcriptomic analysis at 48 h postmortem: a proof of concept for the identification of biomarkers to estimate time since death.

BACKGROUND: The postmortem interval (PMI) refers to the time elapsed between an individual's death and the examination of the body. Tissues undergo a sequence of anatomical changes following death, which are routinely used to estimate the PMI. METHODS: To determine if these anatomical changes are associated with identifiable genomic adaptations that could characterize the PMI more accurately, we analyzed the rat skeletal muscle transcriptome at 0 and 48 h postmortem using Clariom™ S arrays. This study investigates whether specific transcriptomic changes correlate with PMI progression, offering a potential molecular tool to complement established anatomical methods. RESULTS: A total of 3,873 differentially expressed mRNAs were identified, of which 2,787 downregulated and 1,086 upregulated transcripts. The most significantly downregulated mRNA was Tnni1 (FC = -30.95, p = 1 × 10-3), while the most upregulated were mt-ATP6, mt-ATP8, and mt-CO3 (FC > 7.78, p < 1.36 × 10-12). Gene ontology (GO) enrichment analyses revealed that mRNAs upregulated at 48 h in the PMI were primarily associated with vascular and endothelial processes, including nitric oxide transport and angiogenesis. Conversely, downregulated mRNAs were linked to mitochondrial activity and cellular metabolism, reflecting both a transient vascular response and metabolic pathway shutdown in the rat skeletal muscle. CONCLUSION: Our results demonstrate significant transcriptomic changes at 48 h postmortem, highlighting specific genes and biological pathways that may serve as candidate biomarkers for PMI estimation.

Animals↗

PubMed2026

Tazarotene-Induced Gene 2 Promotes Melanoma Cell Death via the Activation of Endoplasmic Reticulum Stress.

BACKGROUND: Tazarotene-induced gene 2 (TIG2), also known as retinoic acid receptor responder 2 (RARRES2), encodes the secreted protein TIG2, also known as chemerin, which is involved in immune regulation and metabolism. However, its role in melanoma remains unclear. METHODS: TIG2 expression was analyzed using The Cancer Genome Atlas, Genotype-Tissue Expression, OncoDB, and melanoma tissue cDNA arrays. To evaluate its effects on cell viability and death, TIG2 was overexpressed in A2058 and A375 melanoma cells. RNA sequencing (RNA-seq), qPCR, and Western blotting were performed to identify TIG2-regulated genes and signaling pathways. The involvement of chemokines and endoplasmic reticulum (ER) stress was further examined using the C-X-C motif chemokine ligand 10 (CXCL 10)/CXCL11 and the ER stress inhibitor tauroursodeoxycholic acid (TUDCA). RESULTS: TIG2 expression was reduced in melanoma and other skin cancers. TIG2 overexpression significantly reduced cell viability and induced cell death. RNA-seq analysis showed that TIG2 downregulated CXCL10, CXCL11, and CCL2 while upregulating ER stress-related genes such as HERPUD1 and DDIT3. Exogenous CXCL10 or CXCL11 did not reverse TIG2-mediated effects, whereas TUDCA partially restored cell viability and reduced cell death. CONCLUSIONS: These findings suggest that TIG2 suppresses melanoma cell growth by activating ER stress and modulating immune-related chemokines, highlighting its potential therapeutic relevance.

Endoplasmic Reticulum Stress↗

PubMed2026

Pervasive positive selection on X-linked ampliconic genes in primates.

Mammalian sex chromosomes harbour ampliconic gene families, which are multi-copy genes with ≥97% sequence identity, predominantly expressed in testis tissue and essential for male fertility. The amplification of testis-specific genes is conserved across mammals, yet the specific gene families that expand show striking lineage-specific variation. Previous studies suggest a dynamic turnover with adaptive evolution for several of these families, but their analysis has been limited by the quality of reference genomes of repetitive regions. To characterise the molecular evolutionary processes of ampliconic gene families on both sex chromosomes, we analysed telomere-to-telomere genome assemblies from eight primate species spanning 25 million years of evolution. We identified 53 X-linked and 19 Y-linked ampliconic gene families with dynamic copy number variation. Gene conversion through palindromic pairing and tandem arrays maintained high sequence similarity despite accumulating mutations. X-linked families maintained conserved chromosomal positions despite copy number changes, whereas Y-linked families showed frequent positional turnover. Strikingly, multiple X-linked families (GAGE, SSX, CSAG, and VCX) showed pervasive positive selection across the primate phylogeny and multiple (MAGEB, CT45, HSFX) showed lineage specific positive selection. Y-linked families predominantly evolve under purifying selection. Examining intraspecific copy number variation of the X-linked ampliconic families in chimpanzees, humans, and gorillas, we found variation among individuals but clear differences between species, with the largest families varying the most. These patterns could suggest that sperm competition, meiotic drive, or dosage-dependent selection drive the rapid, lineage-specific evolution of testis-expressed ampliconic genes in primates.

Journal Article↗