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PubMed2026

In silico analysis of SH3BP2 genomic alterations and expression profiles in CRC.

AIM: Colorectal cancer (CRC) is a widespread health issue that attains high mortality. The adaptor protein SH3BP2 amplification results in metabolic changes, oxidative stress, NK cell activity, and inflammation. The NK cells are capable of destroying tumor cells without prior activation, help prevent metastasis, and have prognostic value. Targeting SH3BP2 to regulate NK cell activity in the TME could enhance CRC-based immunotherapy. MATERIALS AND METHODS: The cancer hallmark tool helps in understanding SH3BP2 hallmark annotation. Utilizing the STRING tool and the KEGG pathway, protein functional enrichment and PPI networking were analyzed. TIMER 2.0 was used for immune cell infiltration correlation analysis, and UALCAN was used for CPTAC-based protein expression profiling. RESULTS AND CONCLUSIONS: The GEO (GSE9348) dataset showed SH3BP2 is upregulated in CRC (log2 fold change = 1.18). GEO, TCGA, and cBioPortal revealed SH3BP2 alterations in CRC cases, potentially aiding immune evasion. Mutations in SH3BP2 influence cancer growth, suppressing tumors or promoting them by activating NF-κB and affecting immune responses through WNT/β-catenin, PI3K, MAPK, and JAK-STAT pathways. Overall, SH3BP2 plays a key role in cancer growth and immune regulation, making it a promising target for CRC therapy. Further experimental validation is needed to demonstrate its diagnostic and therapeutic potency.

Humans↗
PubMed2006

The evolutionary rate of a protein is influenced by features of the interacting partners.

Rates of protein evolution are thought to be influenced by features of protein-protein interaction (PPI). However, the most important features of interaction for determining the evolutionary rate are poorly understood. Here, we consider four categories for PPIs in Saccharomyces cerevisiae. Properties we consider are the extent to which proteins interact with proteins of the same function or different function (DF) and the extent to which these interactions involve connections in the dense part or sparse part (SP) of a PPI network. Our findings are that proteins with DF-SP interactions evolve at the slowest rate of all the proteins examined.

Cluster Analysis↗
PubMed2003

The PEDANT genome database.

The PEDANT genome database (http://pedant.gsf.de) provides exhaustive automatic analysis of genomic sequences by a large variety of established bioinformatics tools through a comprehensive Web-based user interface. One hundred and seventy seven completely sequenced and unfinished genomes have been processed so far, including large eukaryotic genomes (mouse, human) published recently. In this contribution, we describe the current status of the PEDANT database and novel analytical features added to the PEDANT server in 2002. Those include: (i) integration with the BioRS data retrieval system which allows fast text queries, (ii) pre-computed sequence clusters in each complete genome, (iii) a comprehensive set of tools for genome comparison, including genome comparison tables and protein function prediction based on genomic context, and (iv) computation and visualization of protein-protein interaction (PPI) networks based on experimental data. The availability of functional and structural predictions for 650 000 genomic proteins in well organized form makes PEDANT a useful resource for both functional and structural genomics.

Animals↗
PubMed2006

Gene loss rate: a probabilistic measure for the conservation of eukaryotic genes.

The rate of conservation of a gene in evolution is believed to be correlated with its biological importance. Recent studies have devised various conservation measures for genes and have shown that they are correlated with several biological characteristics of functional importance. Specifically, the state-of-the-art propensity for gene loss (PGL) measure was shown to be strongly correlated with gene essentiality and its number of protein-protein interactions (PPIs). The observed correlation between conservation and functional importance varies however between conservation measures, underscoring the need for accurate and general measures for the rate of gene conservation. Here we develop a novel maximum-likelihood approach to computing the rate in which a gene is lost in evolution, motivated by the same principles as those underlying PGL. However, in difference to PGL which considers only the most parsimonious ancestral states of the internal nodes of the phylogenetic tree relating the species, our approach weighs in a probabilistic manner all possible ancestral states, and includes the branch length information as part of the probabilistic model. In application to data of 16 eukaryotic genomes, our approach shows higher correlations with experimental data than PGL, including data on gene lethality, level of connectivity in a PPI network and coherence within functionally related genes.

Algorithms↗
PubMed2026

Mitochondria-Related Pathogenic Genes in Paediatric Asthma: A Multi-Omics Mendelian Randomization Study.

Mitochondrial dysfunction is implicated in asthma pathogenesis, but causal roles of mitochondrial-related genes in paediatric asthma remain unclear. We performed a multi-omics Mendelian randomization study integrating GWAS data from paediatric asthma cohorts with blood-based methylation quantitative trait loci (mQTLs), expression QTLs (eQTLs) and protein QTLs (pQTLs) datasets. Causal inference was assessed using Summary-data-based Mendelian Randomization (SMR) and HEIDI testing, complemented by colocalization analysis. Findings were validated in independent cohorts and evaluated for tissue specificity using GTEx. Functional enrichment and protein-protein interaction (PPI) network analyses were conducted. SMR analysis identified 80 methylation sites spanning 54 genes, 26 gene expressions, and three proteins significantly associated with paediatric asthma. Colocalization analysis confirmed strong evidence for 10 methylation sites (7 genes), the STX17 eQTL (PP.H4 = 0.98) and the UNG pQTL (PP.H4 = 0.84). Tissue-specific eQTL validation replicated the STX17 association. Multi-omics integration associated ALAS1 (cg13241645, cg15698299) and TXNRD1 (cg09884423) with asthma at both methylation and expression levels, with colocalization supporting both ALAS1 associations. Furthermore, integrated mQTL-eQTL analysis suggests that DNA methylation potentially regulates ALAS1 and TXNRD1 expression. Functional enrichment and network analyses revealed that these candidate genes converge on mitochondrial metabolic pathways and identified seven hub genes with potential regulatory significance (SDHB, MFN2, GLDC, PHB2, TXNRD1, ATP5MC1 and PHB). This study provides multi-omics evidence supporting a causal role for mitochondrial-related genes, particularly ALAS1 and TXNRD1, in paediatric asthma, offering new insights into pathogenesis and potential therapeutic targets.

Humans↗
PubMed2006

Evolutionary conservation of domain-domain interactions.

BACKGROUND: Recently, there has been much interest in relating domain-domain interactions (DDIs) to protein-protein interactions (PPIs) and vice versa, in an attempt to understand the molecular basis of PPIs. RESULTS: Here we map structurally derived DDIs onto the cellular PPI networks of different organisms and demonstrate that there is a catalog of domain pairs that is used to mediate various interactions in the cell. We show that these DDIs occur frequently in protein complexes and that homotypic interactions (of a domain with itself) are abundant. A comparison of the repertoires of DDIs in the networks of Escherichia coli, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens shows that many DDIs are evolutionarily conserved. CONCLUSION: Our results indicate that different organisms use the same 'building blocks' for PPIs, suggesting that the functionality of many domain pairs in mediating protein interactions is maintained in evolution.

Animals↗
PubMed2020

Genetic variants in migraine: a field synopsis and systematic re-analysis of meta-analyses.

OBJECTIVE: Numerous genetic variants from meta-analyses of observational studies and GWAS were reported to be associated with migraine susceptibility. However, due to the random errors in meta-analyses, the noteworthiness of the results showing statistically significant remains doubtful. Thus, we performed this field synopsis and re-analysis study to evaluate the noteworthiness using a Bayesian approach in hope of finding true associations. METHODS: Relevant meta-analyses from observational studies and GWAS examining correlation between all genetic variants and migraine risk were included in our study by a PubMed search. Identification of noteworthy associations were analyzed by false-positive rate probability (FPRP) and Bayesian false discovery probability (BFDP). Using noteworthy variants, GO enrichment analysis were conducted through DAVID online tool. Then, the PPI network and hub genes were performed using STRING database and CytoHubba software. RESULTS: As for 8 significant genetic variants from observational studies, none of which showed noteworthy at prior probability of 0.001. Out of 47 significant genetic variants in GWAS, 36 were noteworthy at prior probability of 0.000001 via FPRP or BFDP. We further found the pathways "positive regulation of cytosolic calcium ion concentration" and "inositol phosphate-mediated signaling" and hub genes including MEF2D, TSPAN2, PHACTR1, TRPM8 and PRDM16 related to migraine susceptibility. CONCLUSION: Herein, we have identified several noteworthy variants for migraine susceptibility in this field synopsis. We hope these data would help identify novel genetic biomarkers and potential therapeutic target for migraine.

Bayes Theorem↗
PubMed2025

Unravelling the transcriptomic characteristics of bronchoalveolar lavage in post-covid pulmonary fibrosis.

BACKGROUND: Post-Covid Pulmonary Fibrosis (PCPF) has emerged as a significant global issue associated with a poor quality of life and significant morbidity. Currently, our understanding of the molecular pathways of PCPF is limited. Hence, in this study, we performed whole transcriptome sequencing of the RNA isolated from the bronchoalveolar lavage (BAL) samples of PCPF and compared it with idiopathic pulmonary fibrosis (IPF) and non-ILD (Interstitial Lung Disease) control to understand the gene expression profile and associated pathways. METHODS: BAL samples from PCPF (n = 3), IPF (n = 3), and non-ILD Control (n = 3) (individuals with apparent healthy lung without interstitial lung disease) groups were obtained and RNA were isolated for whole transcriptomic sequencing. Differentially Expressed Genes (DEGs) were determined followed by functional enrichment analysis and qPCR validation. RESULTS: A panel of differentially expressed genes were identified in bronchoalveolar lavage fluid cells (BALF) of PCPF as compare to control and IPF. Our analysis revealed dysregulated pathways associated with cell cycle regulation, immune responses, and neuroinflammatory processes. Real-time validation further supported these findings. The PPI network and module analysis shed light on potential biomarkers and underscore the complex interplay of molecular mechanisms in PCPF. The comparison of PCPF and IPF identified a significant downregulation of pathways that were more prominent in IPF. CONCLUSION: This investigation provides crucial insights into the molecular mechanism of PCPF and also outlines avenues for prospective research and the development of therapeutic approaches.

Humans↗
PubMed2026

Discovery and validation of a prognostic SPP1/PLAU signature in HPV-negative oropharyngeal squamous cell carcinoma.

BACKGROUND: This study aimed to identify and validate robust prognostic biomarkers for oropharyngeal squamous cell carcinoma (OPSCC), with a specific focus on the high-risk HPV-negative subtype. METHODS: Integrated bioinformatics analysis was performed on transcriptomic data from four GEO datasets (n&#x2009;=&#x2009;418 samples). Differentially expressed genes (DEGs) were identified, and a protein-protein interaction (PPI) network was constructed for the most dysregulated genes. Key modules were analyzed via survival analysis and multivariate Cox regression. The top candidate genes were validated at the protein level using immunohistochemistry (IHC) in an independent cohort of 304 OPSCC patients. RESULTS: A 33-gene module related to extracellular matrix organization showed significant prognostic association. It stratified patients into high- and low-risk groups with markedly different overall survival (HR&#x2009;=&#x2009;2.71, p&#x2009;<&#x2009;0.001). From this module, SPP1 and PLAU were identified as independent prognostic factors through multi-step screening. Both genes were significantly overexpressed in tumors (approximately 20-fold and 10-fold, respectively, p&#x2009;<&#x2009;0.001), with high expression strongly correlated with advanced tumor stage (p&#x2009;<&#x2009;0.01) and, notably, the HPV-negative subtype (p&#x2009;<&#x2009;0.001). In survival analysis, high expression of either SPP1 or PLAU was associated with poorer overall survival (SPP1: p&#x2009;<&#x2009;0.001; PLAU: p&#x2009;<&#x2009;0.001) and progression-free survival (p&#x2009;<&#x2009;0.001). IHC validation confirmed high protein expression in 69.7% (SPP1) and 54.8% (PLAU) of cancer tissues. A prognostic nomogram integrating the SPP1/PLAU signature with clinical variables was constructed with strong predictive accuracy (C-index&#x2009;=&#x2009;0.75). CONCLUSION: The SPP1/PLAU dual-gene signature is a robust and independent prognostic biomarker for OPSCC, with particular clinical utility for stratifying high-risk HPV-negative patients.

Humans↗
PubMed2025

Possible linking and treatment between Parkinson's disease and inflammatory bowel disease: a study of Mendelian randomization based on gut-brain axis.

BACKGROUND: Mounting evidence suggests that Parkinson's disease (PD) and inflammatory bowel disease (IBD) are closely associated and becoming global health burdens. However, the causal relationships and common pathogeneses between them are uncertain. Furthermore, they are uncurable. Thus, we aimed to identify the causal relationships and novel therapeutic targets shared between them based on their common pathophysiological mechanisms in gut-brain-axis (GBA). METHODS: A meta-analysis on bidirectional Mendelian randomization (MR) utilizing various datasets was performed to estimate their causal relationship. Then, pleiotropic analysis under the composite null hypothesis (PLACO) with functional mapping combined with annotation of genetic associations (FUMA) analysis were conducted to identify pleiotropic genes. Next, blood, brain and intestine expression quantitative trait locus (eQTL) were taken to perform drug-target MR finding common causal genes in two diseases. Colocalization analysis ensured the eQTLs of corresponding gene colocalized with disease. Enrichment analysis and protein&#x2012;protein interaction (PPI) network were done to explore common pathogenesis pathways. Genes passed all analysis were regarded as drug targets. RESULTS: Our MR meta-analysis revealed the bidirectional causal relationship between diseases, with combined ORs for PD on IBD, CD, UC (1.050 [95% CI 1.014-1.086], 1.044 [95% CI 0.995-1.095], 1.063 [95% CI 1.016-1.120]); for IBD, CD, UC on PD (1.003 [95% CI 0.973-1.034], 1.035 [95% CI 1.004-1.067], 1.008 [95% CI 0.977-1.040]). Overall, 277, 216 and 201 genes were identified as pleiotropic genes between PD and IBD, CD, UC. Total of 733 genes were classified as tier 3 (found in only one tissue) druggable targets, 57 as tier 2 (found in two tissues, 51 protein-coding genes) and 9 as tier 3 (found in three tissues). Among 60 protein-coding druggable targets over tier 2, 18 overlapped with pleiotropic genes and enriched in mitochondria, antigen presentation, processing and immune cell regulation pathways. Three druggable genes (LRRK2, RAB29 and HLA-DQA2) passed colocalization analysis. LRRK2 and RAB29 were reported to be pleiotropic genes, and RAB29 and HLA-DQA2 were reported for the first time as potential drug targets. CONCLUSIONS: This study established a reliable causal relationship, possible shared drug targets and common pathogenesis pathways of two diseases, which had important implications for intervention and treatment of two diseases simultaneously.

Humans↗
PubMed2025

Tumor Signatures of Physical Fitness: Insights from a Preclinical Model.

PURPOSE: Cardiorespiratory fitness (CRF) and muscle strength are associated with cancer risk/mortality in adults. However, there is yet no evidence for pediatric tumors. This study investigated the association of CRF and muscle strength with several tumor-related phenotypes in an aggressive childhood malignancy, high-risk neuroblastoma. METHODS: Twelve mice-bearing orthotopic high-risk neuroblastomas were studied. CRF and muscle strength were assessed using treadmill and grip strength testing, respectively. The following tumor-related outcomes were studied: survival, clinical severity, tumor weight/volume, metastasis, and intratumor immune infiltrates. In addition, tumor samples underwent quantitative proteomic analysis via liquid chromatography-tandem mass spectrometry. Spearman correlations (or logistic regression) were performed between CRF/muscle strength and the abovementioned variables. Proteins that were significantly correlated with CRF or muscle strength were mapped into protein-protein interaction (PPI) networks using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. RESULTS: CRF was inversely correlated with clinical severity score ( r = -0.657, P = 0.020). Of 6840 identified tumor proteins, 76 correlated significantly with CRF (19 positively, 57 negatively), whereas 194 correlated with muscle strength (97 positively, 97 negatively). Proteins correlated with CRF were primarily involved in metabolic and structural pathways, including angiotensinogen and elastin. In turn, muscle strength-associated proteins were more abundant and included keratin family proteins (e.g., keratin, type I cytoskeletal 14, and type II cytoskeletal 5), proteins involved in cell adhesion (e.g., desmoglein-1-alpha), and translational regulators (e.g., eukaryotic initiation factor 4A). Network analysis revealed significant enrichment in structural organization and cellular adhesion pathways. CONCLUSIONS: Besides the association of CRF with clinical severity of the tumor, distinct novel tumor proteomic signatures associated with CRF and muscle strength were identified, highlighting potential mechanisms linking physical fitness with childhood cancer biology.

Muscle Strength↗
PubMed2026

Mechanisms by which carbamoylated high-density lipoprotein (C-HDL) promotes calcific aortic valve disease and exploration of potential targeted therapies.

Calcific aortic valve disease (CAVD) is a progressive fibrocalcific illness for which no effective pharmaceutical treatment exists. This study investigated whether carbamoylated high-density lipoprotein (C-HDL), a defective type of HDL that can develop during inflammation, contributes to CAVD progression and the involved molecular pathways. Male ApoE-/- mice were divided into three groups: CAVD model, cyanate-treated, and inhibitor, and analyzed after 12&#x202f;weeks. C57BL/6 mice on a regular diet served as blank controls. Serum paraoxonase-1 (PON1), aortic valve calcification, cluster of differentiation 31 (CD31), phosphorylated nuclear factor kappa B p65 (p-p65), NOTCH receptor 1 (NOTCH1), and runt-related transcription factor 2 (RUNX2) were evaluated. In parallel, using RNA sequencing (RNA-seq), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, protein-protein interaction (PPI) network analysis, and quantitative real-time polymerase chain reaction. Cyanate treatment reduced serum PON1 levels, increased von Kossa-positive calcium deposition, and raised CD31, p-p65, NOTCH1, and RUNX2 levels compared with the model group, but Gly partially corrected these effects. Transcriptomic research identified 270 C-HDL-associated differentially expressed genes (DEGs) enriched in pathways associated with inflammatory signaling and NF-&#x3ba;B activity. Five potential hub genes (BIRC6, PIK3R1, ATM, IFIH1, and DDX58) were discovered and verified using qRT-PCR. These data show that C-HDL may accelerate CAVD by disrupting valve endothelial homeostasis and stimulating inflammatory signaling, and they identify potential molecular targets for future functional validation.

bioinformatics↗
PubMed2026

Furmonertinib inhibits non-small cell lung cancer progression through ANGPT1-mediated regulation of cell migration and apoptosis.

BACKGROUND: Lung cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for effective therapeutic agents. This study investigates the antitumor effects and underlying mechanisms of furmonertinib (FUR) in lung cancer cells. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to identify FUR target genes, followed by functional enrichment, survival, and protein-protein interaction (PPI) network analyses. Human lung cancer cell line A549 was treated with FUR and/or ANGPT1-specific siRNA. Cell migration, apoptosis, and protein expression were assessed by wound healing, flow cytometry, and Western blotting. Cellular thermal shift assay (CETSA) and drug affinity response target stability (DARTS) assays were used to assess FUR-induced stabilization of angiopoietin-1 (ANGPT1) protein. RESULTS: FUR treatment significantly inhibited cell migration and increased apoptosis in NSCLC cells. Bioinformatics analysis revealed 12 overlapping target genes of FUR from the PharmMapper and SwissTargetPrediction databases, with ANGPT1 emerging as a key candidate. ANGPT1 expression was downregulated in tumor tissues and positively correlated with patient survival. Western blotting confirmed that FUR upregulated ANGPT1 protein levels in a dose-dependent manner. Knockdown of ANGPT1 enhanced migration and suppressed apoptosis, while FUR reversed these effects. FUR treatment enhanced the stability of ANGPT1 under high-temperature conditions while reducing its sensitivity to protease. ANGPT1 may have affected tumor cell migration through cell adhesion and extracellular matrix (ECM) pathways. CONCLUSIONS: FUR suppresses lung cancer progression by upregulating ANGPT1, thereby inhibiting cell migration and promoting apoptosis. ANGPT1 is a potential therapeutic target and provides new insights into the anti-tumor mechanism of FUR in lung cancer.

Lung cancer↗
PubMed2026

Exploring the Genetic Link between Irritable Bowel Syndrome and Polycystic Ovary Syndrome: Bidirectional Mendelian Randomization and Machine Learning Approaches.

BACKGROUND: Research has shown a certain correlation between polycystic ovary syndrome (PCOS) and irritable bowel syndrome (IBS). The study aims to determine the directionality and underlying biological processes influencing the relationship between these two disorders. METHODS: We explored the causal relationship between IBS and PCOS by conducting a comprehensive bidirectional Mendelian randomization (MR) analysis using five different methods and conducted robustness assessments. We extracted differentially expressed genes from the IBS and PCOS datasets for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Additionally, we developed a protein-protein interaction (PPI) network and applied the Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine (SVM) methodologies to pinpoint key diagnostic markers. Diagnostic efficacy was further assessed through Receiver Operating Characteristic (ROC) curve analysis for selected genes. Finally, single-sample gene set enrichment analysis (ssGSEA) was carried out to examine immune cell infiltration in IBS and PCOS. RESULTS: MR analysis identified a causal effect of PCOS on IBS (IVW, OR = 1.034, 95% CI: 1.003-1.065, P = 0.029). Conversely, no relationship between IBS and PCOS was observed in the reverse analysis. Furthermore, integrative bioinformatics and machine learning analyses identified CD14 and CASP1 as key diagnostic biomarkers for both IBS and PCOS, which were significantly associated with immune cell infiltration. CONCLUSION: MR analysis has demonstrated a significant positive causal relationship between PCOS and IBS, though the reverse causality from IBS to PCOS appeared non-significant. The genes CD14 and CASP1 emerged as potential shared diagnostic markers between these two conditions.

Polycystic Ovary Syndrome↗
PubMed2026

IL1B-centered immune dysregulation involving IL7R, CCR7, ITGB2 and IRF1 across insomnia and inflammatory bowel disease.

BACKGROUND: Insomnia is a prevalent sleep disorder that strongly affects one's quality of life and physical well-being. Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the intestines, and a majority of IBD patients suffer from comorbid insomnia. However, the shared molecular features linking insomnia and IBD remain poorly characterized. METHODS: Common differentially expressed genes (DEGs) were identified in datasets of insomnia (GSE208668) and IBD (GSE179285) using the Limma package. Functional enrichment was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Protein-protein interaction (PPI) network construction and hub gene identification was subsequently performed. Furthermore, we validated the reliability of the hub genes using qRT-PCR and Enzyme-linked immunosorbent assay (ELISA). In addition, we constructed a TF-miRNA regulatory network of hub genes and assessed the abundance of immune cell infiltration in insomnia and IBD using CIBERSORT, EPIC, and xCell algorithms. Finally, we utilized the DsigDB to predict potential therapeutic candidates. RESULTS: The analysis revealed 75 upregulated and 32 downregulated common DEGs. Functional enrichment analysis revealed the inflammatory response and immune activation as pivotal drivers underlying the pathogenesis of both insomnia and IBD. Five hub DEGs, namely, IL1B, IL7R, CCR7, ITGB2, and IRF1, were subsequently screened and validated. The TF-miRNA-mRNA regulatory network consisted of 5 TFs, 14 miRNA nodes and 5 core mRNA nodes. Immune cell infiltration analysis revealed several patterns shared between insomnia and IBD. Additionally, 10 potential therapeutic drugs for insomnia and IBD were proposed. CONCLUSION: Integrative coexpression network analysis reveals convergent dysregulation of an IL1B-centered immune module (comprising IL7R, CCR7, ITGB2, and IRF1) across insomnia and IBD, a shared immune disturbance and candidate targets for simultaneous intervention upon further mechanistic validation.

Humans↗
PubMed2026

Integrative subtyping by bile acid metabolism identifies CLCA1/UGT2A3/ZG16 as markers of immune dysfunction and poor prognosis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the primary driver of cancer-related death and illness across the world. Despite the full-scale shift of the treatment approach for some colorectal cancer patients due to the use of immune checkpoint inhibitors (ICIs), primary resistance still poses a huge challenge to clinicians. Bile acid metabolism is involved in the pathogenesis of CRC. However, its particular function in shaping the tumor immune microenvironment (TIME) and its effect on prognosis and immune treatment response remain unclear. METHODS: Based on the transcriptome and clinical data from The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) cohort, we performed unsupervised consensus clustering and classified patients into different molecular subtypes according to bile acid metabolism. We subsequently compared overall survival (OS), immune cell infiltration levels, and differentially expressed genes among the subtypes. In addition, protein-protein interaction (PPI) network and Cox proportional hazards regression were used to identify key hub genes. Finally, the expression of these crucial hub genes was validated in the Gene Expression Omnibus (GEO) cohort and independent clinical patients. RESULTS: The bile-low group showed a significant reduction in OS time (p = 0.0049). The infiltration levels of CD8+ T cells (p < 0.05) and M1 macrophages (p < 0.01) were significantly higher in the bile-low group than in the bile-high group. We identified three key genes-CLCA1, UGT2A3, and ZG16-and found that they all were downregulated in tumor tissues across the TCGA-COAD and GEO datasets, as well as in independent clinical samples. Survival analysis showed that high CLCA1 expression was significantly associated with favorable overall survival (p < 0.001), whereas UGT2A3 (p = 0.23) and ZG16 (p = 0.17) did not reach statistical significance. The three hub genes were negatively correlated with the (TIDE) score (CLCA1: R = - 0.24, p < 0.001; UGT2A3: R = - 0.15, p = 0.0022; ZG16: R = - 0.14, p = 0.0039). CONCLUSION: Our findings suggest that bile acid metabolism could shape the TIME via key genes CLCA1, UGT2A3, and ZG16, and subsequently modify CRC prognosis and immunotherapy responses. These genes may serve as potential prognostic indicators and mechanistic mediators linking bile acid metabolism to T-cell dysfunction, offering insights for future combination strategies targeting the metabolism-barrier-immunity axis.

CLCA1↗
PubMed2026

Bioinformatics and Quantitative Real-Time Polymerase Chain Reaction Analysis of SUCNR1 and GPR37L1 in Schizophrenia.

Schizophrenia is a severe, complex, and multifactorial mental disorder involving numerous genetic susceptibility elements, leading to substantial disability, morbidity, and mortality. Despite significant progress in understanding its pathophysiology and etiology, specific diagnostic biomarkers for schizophrenia remain elusive. This study aimed to identify candidate molecular markers associated with schizophrenia. An integrated bioinformatics analysis was performed on the public microarray dataset GSE54913. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the most significantly enriched GO terms were related to channel activity, including passive transmembrane transporter activity, ion channel activity, gated channel activity, and substrate-specific channel activity. The top five enriched KEGG pathways were insulin secretion, cAMP signaling pathway, nucleotide excision repair, TNF signaling pathway, and glutathione metabolism. Validation was conducted using quantitative real-time polymerase chain reaction (qRT-PCR) on an independent sample set from Wuhan Rongjun Youfu Hospital. The qRT-PCR results were largely consistent with the microarray analysis (Pearson r = 0.89, 95% CI: 0.66-0.97). Protein-protein interaction (PPI) network analysis identified two hub genes, SUCNR1 and GPR37L1, which were significantly associated with the GO term 'ion channel activity' and enriched in the KEGG pathway 'insulin secretion'. Furthermore, SUCNR1 expression showed a negative correlation with verbal memory scores (r = -0.54, P = 0.015), whereas GPR37L1 expression showed a positive correlation (r = 0.59, P = 0.0034). These findings suggest that altered SUCNR1 and GPR37L1 expression may be associated with schizophrenia and may represent candidate molecular markers for further investigation.

Humans↗