Potential Diagnostic Biomarkers Research Articles

METTL14-mediated m6A mRNA modification of G6PD promotes lung adenocarcinoma

METTL14 functions as an RNA methyltransferase involved in m6A modification, influencing mRNA biogenesis, decay, and translation processes. However, the specific mechanism by which METTL14 regulates glucose-6-phosphate dehydrogenase (G6PD) to promote the progression of lung adenocarcinoma (LUAD) is not well understood. Quantitative measurement and immunohistochemistry (IHC) analysis have demonstrated higher levels of m6A in LUAD tissues compared to adjacent normal tissues. Additionally, the expression of METTL14 was significantly increased in LUAD tissues. In LUAD cell lines, both METTL14 and m6A levels were elevated compared to normal human lung epithelial cells. Knockdown of METTL14 markedly reduced LUAD cell proliferation, migration, and invasion. Conversely, overexpression of METTL14, but not the mutant form, significantly enhanced these cellular processes in LUAD. In vivo studies using nude mice with subcutaneously transplanted LUAD cells demonstrated that stable METTL14 knockdown led to notably reduced tumor volume and weight, along with fewer Ki67-positive cells and lung metastatic sites. Importantly, METTL14 knockdown reduced glycolytic activity in LUAD cells. Through a combination of RNA sequencing and MeRIP-sequencing, we identified numerous altered genes and confirmed that IGF2BP2 enhances G6PD mRNA stability after METTL14-mediated m6A modification, thereby promoting tumor growth and metastasis. Moreover, LUAD patients with higher levels of G6PD had poorer overall survival (OS). In conclusion, our study indicates that METTL14 upregulates G6PD expression post-transcriptionally through an m6A-IGF2BP2-dependent mechanism, thereby stabilizing G6PD mRNA. These findings propose potential diagnostic biomarkers and effective targets for anti-metabolism therapy in LUAD.

EIF4A3-Induced Upregulation of hsa_circ_0049396 Attenuates the Tumorigenesis of Nasopharyngeal Carcinoma by Regulating the Hippo-YAP Pathway.

Circular RNAs (circRNAs) and eukaryotic translation initiation factor 4A3 (EIF4A3) have been reported to participate in the pathogenesis of nasopharyngeal carcinoma (NPC), but their mechanism has not been fully understood. This research aimed to confirm the role and regulatory mechanism of hsa_circ_0049396 interacting with EIF4A3 in NPC tumorigenesis. Quantitative real time polymerase chain reaction (qRT-PCR) was executed to detect the levels of hsa_circ_0049396 and EIF4A3. Cell function experiments and nude mice xenograft assay were used to confirm the role of hsa_circ_0049396 in NPC. The regulatory effect of EIA4A3 on hsa_circ_0049396 was determined by circInteractome prediction, RNA binding protein immunoprecipitation (RIP) assay, and qRT-PCR. In addition, the Hippo-YAP pathway-related proteins and EIF4A3 protein were detected by western blotting. hsa_circ_0049396 was proved to be downregulated in NPC samples, and its low expression indicated the poor prognosis of NPC. After upregulating hsa_circ_0049396 in NPC cells, the proliferation, migration, invasion, and tumor growth invivo were suppressed by inhibiting the Hippo-YAP pathway. Moreover, EIF4A3 bound to the flanking regions of the hsa_circ_0049396 to enhance hsa_circ_0049396 expression in NPC cells. hsa_circ_0049396 mediated by EIF4A3 in NPC can attenuate NPC tumorigenesis by inhibiting the Hippo-YAP pathway. This finding may provide a potential early diagnostic biomarker or drug target to improve the precision medicine approaches of NPC.

Urinary GM2AP coincides with renal cortical damage and grades cisplatin nephrotoxicity severity in rats

Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury. However, the standard diagnosis based on plasma creatinine as well as novel injury biomarkers lacks enough pathophysiological specificity. Further granularity in the detection of renal injury would help understand the implications of individual damage patterns needed for personalized patient handling. In this article, we studied the association of urinary ganglioside GM2 activator protein (GM2AP) with the patterns of tubular damage produced by 5 and 10 mg/kg cisplatin in rats. Our results show that GM2AP appears in the urine only following damage to the cortical segment of the proximal tubule. The information provided by GM2AP is not redundant with but distinct and complementary to that provided by urinary neutrophil gelatinase-associated lipocalin (NGAL). Similarly, treatment with 150 mg/kg/day gentamicin damages the renal cortex and increases GM2AP urinary excretion; whereas renal ischemia, which does not affect the cortex, has no effect on GM2AP. Because of the key role of the cortical proximal tubule in renal function, we contend GM2AP as a potential diagnostic biomarker to stratify AKI patients according to the underlying damage and follow their evolution and prognosis. Prospectively, urinary GM2AP may help grade the severity of platinated antineoplastic nephrotoxicity by forming part of a non-invasive liquid biopsy.

Comprehensive pan-cancer analysis of ZNF337 as a potential diagnostic, immunological, and prognostic biomarker

BackgroundZinc Finger Protein 337 (ZNF337) is a novel Zinc Finger (ZNF) protein family member. However, the roles of ZNF337 in human cancers have not yet been investigated.MethodsIn this study, with the aid of TCGA databases, GTEx databases, and online websites, we determined the expression levels of ZNF337 in pan-cancer and its potential value as a diagnostic and prognostic marker for pan-cancer and analyzed the relationship between ZNF337 expression and immune cell infiltration and immune checkpoint genes. We then focused our research on the potential of ZNF337 as a biomarker for diagnostic and prognostic in KIRC (kidney renal clear cell carcinoma) and validated in the E-MTAB-1980 database. Moreover, the expression of ZNF337 was detected through qRT-PCR and Western blotting (WB). CCK-8 experiment, colony formation experiment, and EDU experiment were performed to evaluate cell proliferation ability. Wound healing assay and transwell assay were used to analyze its migration ability. The qRT-PCR and WB were used to detect the expression of ZNF337 in tumor tissues and paracancerous tissues of KIRC patients.ResultsThe pan-cancer analysis revealed that abnormal ZNF337 expression was found in multiple human cancer types. ZNF337 had a high diagnostic value in pan-cancer and a significant association with the prognosis of certain cancers, indicating that ZNF337 may be a valuable prognostic biomarker for multiple cancers. Further analysis demonstrated that the expression level of ZNF337 displayed significant correlations with cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes in many tumors. Additionally, ZNF337 was observed to have a high expression in KIRC. Its expression was significantly associated with poor prognosis [overall survival (OS), disease-specific survival (DSS)], age, TNM stage, histologic grade, and pathologic stage. The high ZNF337 expression was associated with poor prognosis in the E-MTAB-1980 validation cohort. The in vitro experiments suggested that the expression of ZNF337 in KIRC tumor tissues was higher than in adjacent tissues, and ZNF337 knockdown inhibited the proliferation and migration of KIRC cells, whereas overexpression of ZNF337 had the opposite effects.ConclusionsZNF337 might be an important prognostic and immunotherapeutic biomarker for pan-cancer, especially in KIRC.

Molecular signatures of normal pressure hydrocephalus: a large-scale proteomic analysis of cerebrospinal fluid

Given the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimer’s disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.

Anti-TCP1 Antibody Is a Potential Biomarker for Diagnosing Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease caused by autoantibodies. Serum samples from patients with SLE (n = 10) were compared with those from normal controls (NCs, n = 5) using 21K protein chip analysis to identify a biomarker for SLE, revealing 63 SLE-specific autoantibodies. The anti-chaperonin-containing t-complex polypeptide-1 (TCP1) antibody exhibited higher expression in patients with SLE than in NCs. To validate the specificity of the anti-TCP1 antibody in SLE, dot blot analysis was conducted using sera from patients with SLE (n = 100), rheumatoid arthritis (RA; n = 25), Behçet's disease (BD; n = 28), and systemic sclerosis (SSc; n = 30) and NCs (n = 50). The results confirmed the detection of anti-TCP1 antibodies in 79 of 100 patients with SLE, with substantially elevated expression compared to both NCs and patients with other autoimmune diseases. We performed an enzyme-linked immunosorbent assay to determine the relative amounts of anti-TCP1 antibodies; markedly elevated anti-TCP1 antibody levels were detected in the sera of patients with SLE (50.1 ± 17.3 arbitrary unit (AU), n = 251) compared to those in NCs (33.9 ± 9.3 AU), RA (35 ± 8.7 AU), BD (37.5 ± 11.6 AU), and SSc (43 ± 11.9 AU). These data suggest that the anti-TCP1 antibody is a potential diagnostic biomarker for SLE.

Advancing the early detection of canine cognitive dysfunction syndrome with machine learning-enhanced blood-based biomarkers.

Up to half of the senior dogs suffer from canine cognitive dysfunction syndrome (CCDS), the diagnosis method relies on subjective questionnaires such as canine cognitive dysfunction rating (CCDR) scores. Therefore, the necessity of objective diagnosis is emerging. Here, we developed blood-based biomarkers for CCDS early detection. Blood samples from dogs with CCDR scores above 25 were analyzed, and the biomarkers retinol-binding protein 4 (RBP4), C-X-C-motif chemokine ligand 10 (CXCL10), and NADPH oxidase 4 (NOX4) were validated against neurodegenerative models. Lower biomarker levels were correlated with higher CCDR scores, indicating cognitive decline. Machine-learning analysis revealed the highest predictive accuracy when analyzing the combination of RBP4 and NOX4 using the support vector machine algorithm and confirmed potential diagnostic biomarkers. These results suggest that blood-based biomarkers can notably improve CCDS early detection and treatment, with implications for neurodegenerative disease management in both animals and humans.

Long non-coding RNA small nucleolar RNA host gene 8 (SNHG8) sponges miR-34b-5p to prevent sepsis-induced cardiac dysfunction and inflammation and serves as a diagnostic biomarker.

The study aimed to evaluate, for the first time, the diagnostic value of long non-coding RNA (lncRNA) small nucleolar RNA host gene 8 (SNHG8) in sepsis and its molecular mechanisms in sepsis-induced inflammation and cardiac dysfunction. A total of 126 sepsis patients and 81 healthy controls were enrolled. Serum SNHG8 levels were assessed by RT-qPCR. Levels of pro-inflammatory factors were examined via ELISA. The ROC curve was employed to assess the diagnostic significance of SNHG8. Cardiomyocytes were exposed to lipopolysaccharide (LPS) to simulate sepsis-induced cardiac dysfunction in vitro. Cell proliferation and apoptosis were measured through CCK-8 and flow cytometry. Dual luciferase reporter gene assay and RIP assay were conducted to verify the target relationship between SNHG8 and miR-34b-5p. SNHG8 was reduced in sepsis patients (p < 0.05) and negatively correlated with procalcitonin, C-reactive protein, and pro-inflammatory factors (p < 0.05). SNHG8 had outstanding performance in distinguishing sepsis patients from healthy individuals with the AUC of 0.878. Among septic patients, those with cardiac dysfunction had significantly downregulated SNHG8 levels (p < 0.05). For septic patients, SNHG8 was found to be an independent predictor for the occurrence of cardiac dysfunction (HR = 5.466, 95% CI = 2.230-13.397, p < 0.001). Elevated SNHG8 reversed LPS-induced cell apoptosis, and attenuated the over-secretion of inflammatory factors. miR-34b-5p was significantly upregulated in septic patients and negatively correlated with SNHG8, indicating that it acted as a sponge for SNHG8. Reduced SNHG8 is a potential diagnostic biomarker for sepsis. It is involved in sepsis-induced inflammatory response and cardiac dysfunction through sponging miR-34b-5p.

Identification of effective diagnostic genes and immune cell infiltration characteristics in small cell lung cancer by integrating bioinformatics analysis and machine learning algorithms.

To identify potential diagnostic markers for small cell lung cancer (SCLC) and investigate the correlation with immune cell infiltration. GSE149507 and GSE6044 were used as the training group, while GSE108055 served as validation group A and GSE73160 served as validation group B. Differentially expressed genes (DEGs) were identified and analyzed for functional enrichment. Machine learning (ML) was used to identify candidate diagnostic genes for SCLC. The area under the receiver operating characteristic curves was applied to assess diagnostic efficacy. Immune cell infiltration analyses were carried out. There were 181 DEGs identified. The gene ontology analysis showed that DEGs were enriched in 455 functional annotations, some of which were associated with immunity. The kyoto encyclopedia of genes and genomes analysis revealed that there were 9 signaling pathways enriched. The disease ontology analysis indicated that DEGs were related to 116 diseases. The gene set enrichment analysis results displayed multiple items closely related to immunity. ZWINT and NRCAM were screened using ML and further validated as diagnostic genes. Significant differences were observed in SCLC with normal lung tissue samples among immune cell infiltration characteristics. Strong associations were found between the diagnostic genes and immune cell infiltration. This study identified 2 diagnostic genes, ZWINT and NRCAM, that were related to immune cell infiltration by integrating bioinformatics analysis and ML algorithms. These genes could serve as potential diagnostic biomarkers and provide possible molecular targets for immunotherapy in SCLC.

Bioinformatic Analysis Reveals Bone Marrow Kinase as a Potential Diagnostic and Prognostic Biomarker for Multiple Cancer Types.

Bone marrow kinase, or BMX, is alternatively referred to as endothelial tyrosine kinase (Etk). It plays a vital role in the processes of cell proliferation, survival, immune activation, and the modulation of diverse signaling pathways. Since there are few direct comprehensive studies linkingBMX role with multiple cancers, this study aimed to utilize bioinformatic tools to conduct a comprehensive analysis of BMX across multiple cancers, assessing its potential role. Multiple databases including the Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), have been used to explore BMX expression across different cancers, which has been further validated by using Gene Expression Omnibus (GEO) public datasets. In addition, we used the Kaplan-Meier plotter to estimate overall survival and cBioPortal for genetic alterations analysis. This study accommodates several other analyses like clinical parameters, immune cell infiltration, and DNA promoter methylation profiles to evaluate the general role of BMXin several cancers. Results: The present investigation revealed that the BMX gene expression was significantly downregulated and could serve as an effective diagnostic biomarker in five types of cancers, namely breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and rectum adenocarcinoma (READ) (all p < 0.05). Detailed analyses revealed notable downregulation of BMX in various clinical parameters such as age, gender, race, and cancer stage (all p < 0.05). To better understand the immunotherapeutic role of BMX, this investigation further examined the immune infiltration which exhibited positive correlations between BMX expression and the infiltration of immunological cells such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, especially in COAD, LUAD, and LUSC(all p < 0.05).In addition, the present study has demonstrated that diminished BMX gene expression is correlated with an unfavorable prognosis in kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), sarcoma (SARC), and uterine corpus endometrial carcinoma (UCEC); thus BMX gene expression can be used as a prognostic target for these specific cancers. Also, the results showed that the promoter methylation level of BMX was significantly elevated in LUAD and LUSC, whereas it was significantly decreased in BRCA (all p < 0.001). Importantly, our findings of significantly low BMX expression inLUAD and LUSC, along with their methylation profiles suggest that the low expression of BMX across these cancers is due to epigenetic factors. However, genetic alteration analysis revealed that mutations existed in only approximately 2% of the TCGA samples. Our study revealed BMX as a diagnostic biomarker in BRCA, COAD, LUAD, LUSC, and READ and a prognostic biomarker in KIRC, LIHC, SARC, and UCEC. Furthermore, epigenetic variables may have a greater impact on BMX expression levels especially in LUAD and LUSC. This study also emphasized the role of BMX in the infiltration of immune cells, such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, in certain cancers. The BMX expression level highlights the prognostic value and potential therapeutic potential of BMX.

Proteomic Profile of Endometrial Cancer: A Scoping Review.

Proteomics can be a robust tool in protein identification and regulation, allowing the discovery of potential biomarkers. In clinical practice, the management of endometrial cancer can be challenging. Thus, identifying promising markers could be beneficial, helping both in diagnosis and prognostic stratification, even predicting the response to therapy. Therefore, this manuscript systematically reviews the existing evidence of the proteomic profile of human endometrial cancer. The literature search was conducted via Medline (through PubMed) and the Web of Science. The inclusion criteria were clinical, in vitro, and in vivo original studies reporting proteomic analysis using all types of samples to map the human endometrial cancer proteome. A total of 55 publications were included in this review. Most of the articles carried out a proteomic analysis on endometrial tissue, serum and plasma samples, which enabled the identification of several potential diagnostic and prognostic biomarkers. In addition, eight articles were analyzed regarding the identified proteins, where three studies showed a strong correlation, sharing forty-five proteins. This analysis also allowed the identification of the 10 most frequently reported proteins in these studies: EGFR, PGRMC1, CSE1L, MYDGF, STMN1, CASP3 ANXA2, YBX1, ANXA1, and MYH11. Proteomics-based approaches pointed out potential diagnostic and prognostic candidates for endometrial cancer. However, there is a lack of studies exploring novel therapeutic targets.

Development of a genome atlas for discriminating benign, preinvasive, and invasive lung nodules.

To tackle misdiagnosis in lung cancer screening with low-dose computed tomography (LDCT), we aimed to compile a genome atlas for differentiating benign, preinvasive, and invasive lung nodules and characterize their molecular pathogenesis. We collected 432 lung nodule tissue samples from Chinese patients, spanning benign, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA). We performed comprehensive sequencing, examining somatic variants, gene expressions, and methylation levels. Our findings uncovered EGFR and TP53 mutations as key drivers in - early lung cancer development, with EGFR mutation frequency increasing with disease progression. Both EGFR mutations and EGF/EGFR hypo-methylation activated the EGFR pathway, fueling cancer growth. Transcriptome analysis identified four lung nodule subtypes (G1-4) with distinct molecular features and immune cell infiltrations: EGFR-driven G1, EGFR/TP53 co-mutation G2, inflamed G3, stem-like G4. Estrogen/androgen response was associated with the EGFR pathway, proposing a new therapy combining tyrosine kinase inhibitors with antiestrogens. Preinvasive nodules exhibited stem cell pathway enrichment, potentially hindering invasion. Epigenetic regulation of various genes was essential for lung cancer initiation and development. This study provides insights into the molecular mechanism of neoplastic progression and identifies potential diagnostic biomarkers and therapeutic targets for lung cancer.

Assay for interferon gamma release as a novel marker in pediatric patients with systemic lupus erythematosus

BackgroundThe interferon-gamma (IFN-γ) release assay (IGRA) is an important laboratory diagnosis for latent Mycobacterium tuberculosis (TB) infection. The TB-IGRA measures the release of IFN-γ from peripheral blood cells, who are exposed to TB antigen (Ag), mitogen (MT), or negative/nil control (NL) in vitro. While, an exceptional higher TB Ag-NL level will reflect an elevation of peripheral lymphocytes released IFN-γ in a same condition. Therefore, we found that the elevated levels of TB Ag-NL could become a new biomarker for the diagnosis and treatment of pediatric systemic lupus erythematosus (SLE) patients.MethodsWe have analyzed the clinical data of 776 children who are underwent TB-IGRA testing in the Department of Allergy and Rheumatology of Guangzhou Women and Children’s Medical Center from 2018 to 2020. To investigate the association between TB Ag-NL and SLE, we have analyzed the clinical data of 47 SLE patients and TB Ag-NL testing results, and then evaluated the association between TB Ag-NL and SLE disease activity.ResultsThe TB Ag-NL levels were significantly higher in patients with active SLE than those in inactive SLE (p = 0.0002). The TB Ag-NL levels were positively correlated with the SLE disease activity index (SLEDAI) and laboratory diagnosis parameters. The mean value of TB Ag-NL in SLE patients (0.04191 ± 0.07955, IU/mL) were significantly higher than those in patients with juvenile dermatomyositis (JDM) (0.0158 ± 0.0337, IU/mL, p = 0.036), juvenile idiopathic arthritis (JIA) (0.0162 ± 0.0388, IU/mL, p = 0.001), and healthy controls (HC) (0.0001 ± 0.0027, IU/mL, p = 0.0003). Therefore, the elevated TB Ag-NL levels could serve as a potential diagnostic biomarker of SLE, especially for the active SLE.ConclusionThe detection of IFN-γ release levels by the TB-IGRA may be useful to assess SLE disease activity in pediatric patients with active SLE.

Interplay between Wnt signaling molecules and exosomal miRNAs in breast cancer (Review).

Breast cancer (BC) is the most common malignancy in women worldwide. Wnt signaling is involved in tumorigenesis and cancer progression, and is closely associated with the characteristics of BC. Variation in the expression of exosomal microRNAs (miRNAs) modulates key cancer phenotypes, such as cellular proliferation, epithelial‑mesenchymal transition, metastatic potential, immune evasion and treatment resistance. The present review aimed to discuss the importance of Wnt signaling and exosomal miRNAs in regulating the occurrence and development of BC. In addition, the present review determined the crosstalk between Wnt signaling and exosomal miRNAs, and highlighted potential diagnostic biomarkers and therapeutic targets.

Identification of potential diagnostic biomarkers for hypertension via integrated analysis of gene expression and DNA methylation

Objective Hypertension refers to the elevated blood pressure (BP) in arteries, with a BP reading of 140/90 mm Hg or higher in adults. Over 40% of >25-year-old population have suffered from hypertension. Thus, this study aimed to find novel diagnostic biomarkers for hypertension. Methods All hypertension-related mRNA and methylation datasets were downloaded from the GEO database. Liner model method was used to identify differentially expressed genes (DEGs) between hypertension and control groups. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analysis was employed to obtain functional information. CpG sites and the corresponding genes associated with hypertension were screened using epigenome-wide association study (EWAS) analysis. Results There were 37 DEGs between the hypertension group and control group, which were significantly enriched in 84 Biological Process terms, 31 Cellular Component terms, 18 Molecular Function terms and 9 signalling pathways. EWAS results indicated that 1072 CpG sites were associated with hypertension occurrence, corresponding to 1029 genes. After cross-analysis, complement factor D (CFD) and OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) with methylation modification were identified as diagnostic markers for hypertension. Conclusion In conclusion, CFD and OTUB2 were potential biomarkers of hypertension occurrence. Our results will provide more information for hypertension diagnosis and would be more reliable combined with multiple biomarkers.

High expression of COPZ2 is associated with poor prognosis and cancer progression in glioma.

Coatomer protein complex zeta 2 (COPZ2) is a member of heptameric coatomer protein complex I and has been reported to be involved in various tumors. However, COPZ2's potential involvement in glioma remains to be explored. The COPZ2 expression and related clinical data were obtained from The Cancer Genome Atlas (TCGA). TIMER2.0 and the Ualcan database were utilized to assess the COPZ2 expression in various tumors. Univariable, multivariate Cox regression, Kaplan-Meier methods, nomogram analysis, and ROC curve analysis were carried out to assess the relationship of COPZ2 and other prognostic factors with glioma. The LinkedOmics database was used to predict the potential biological mechanism of COPZ2 in glioma. We also conducted in vitro experiments to evaluate the functional role and mechanism of COPZ2 in glioma cell lines. We found that COPZ2 was highly expressed in glioma and it was associated with age and WHO grades. Kaplan-Meier survival curves, Cox analysis, nomogram analysis, and ROC curve showed that COPZ2 was a disadvantageous factor in poor glioma prognosis. The functions of COPZ2 and co-expression genes were significantly associated with neutrophil-mediated immunity, granulocyte activation, and response to interferon-gamma. In addition, COPZ2 knockdown significantly inhibited the proliferation, migration, and invasion of glioblastoma cells. Mechanistically, COPZ2 suppressed tumor development by participating in the regulation of the PI3K-AKT signaling pathway. Our results demonstrated that the elevation of COPZ2 was associated with the prognosis and progression of glioma, and it might be a potential diagnostic and prognostic biomarker for glioma.

Identification of novel biomarkers for childhood-onset systemic lupus erythematosus using machine learning algorithms and immune infiltration analysis.

Childhood-onset systemic lupus erythematosus (cSLE) is a chronic autoimmune disease that is often more severe than adult-onset SLE and is challenging to diagnose due to its variable presentation and lack of specific diagnostic tests. This study aimed to identify potential diagnostic biomarkers for cSLE by analyzing differentially expressed genes (DEGs)using machine learning algorithms. In this study, we utilized the Gene Expression Omnibus database to investigate the DEGs between cSLE and normal samples, conducting a functional enrichment analysis on DEGs. Subsequently, we employed machine learning algorithms, including Least Absolute Shrinkage and Selection Operatorregression and Support Vector Machine-Recursive Feature Elimination, to identify hub DEGs, which serve as crucial biomarkers. We delved into the role of these hub DEGs in the pathogenesis of the disease and the correlation between these hub DEGs and immune infiltration by comprehensive immune infiltration analysis using the CIBERSORT algorithm. We identified 110 DEGs in cSLE, including 95 upregulated and 15 downregulated genes. Functional annotation revealed that these DEGs were involved in immune response processes, viral defense mechanisms, and regulation of interferon responses. Machine learning algorithms identified CCR1 and SAMD9L as hub DEGs, which were validated in multiple datasets and demonstrated high diagnostic value for cSLE. Mechanistic exploration suggested that CCR1 and SAMD9L are involved in immune response modulation, particularly in interferon signaling and the innate immune system. Assessment of immune cell infiltration revealed significant differences in immune cell composition between cSLE patients and healthy controls, with cSLE patients exhibiting a higher proportion of neutrophils. Moreover, CCR1 and SAMD9L expression levels showed positive correlations with neutrophil infiltration and other immune cell types. CCR1 and SAMD9L were identified as potential diagnostic biomarkers for cSLE using machine learning and were validated in multiple datasets. These findings provide novel insights into the biological underpinnings of cSLE.

Quantitative proteomics and immunohistochemistry uncover NT5DC2 as a diagnostic biomarker for papillary urothelial carcinoma

The accurate diagnosis of papillary urothelial carcinoma (PUC) is frequently challenging due to benign mimickers. Other than morphology-based diagnostic criteria, reliable biomarkers for differentiating benign and malignant papillary urothelial neoplasms remain elusive, so we sought to discover new markers to address this challenge. We first performed tandem mass spectrometry-based quantitative proteomics using diverse papillary urothelial lesions, including PUC, urothelial papilloma (UP), inverted urothelial papilloma, and cystitis cystica. We prioritized potential diagnostic biomarkers using machine learning, and subsequently validated through immunohistochemistry (IHC) in two independent cohorts. Metabolism, transport, cell cycle, development, and immune response functions were differentially enriched between malignant and benign papillary neoplasms. RhoB and NT5DC2 were shortlisted as optimal candidate markers for PUC diagnosis. In our pilot study using IHC, NT5DC2 was subsequently selected as its expression consistently differed in PUC (p = 0.007). Further validation of NT5DC2 using 49 low-grade (LG) urothelial lesions, including 15 LG-PUCs and 17 UPs, which are the most common mimickers, concordantly revealed lower IHC expression levels in LG-PUC (p = 0.0298). Independent external validation with eight LG-PUCs and eight UPs confirmed the significant downregulation of NT5DC2 in LG-PUC (p = 0.0104). We suggest that NT5DC2 is a potential IHC biomarker for differentiating LG-PUC from its benign mimickers, especially UP.

Biomarcadores proteómicos para la predicción no invasiva de trombos en la orejuela izquierda de pacientes con fibrilación auricular

Introduction and objectivesThe CHA2DS2-VASc score, used to assess the risk of left atrial appendage thrombus (LAAT) formation in patients with atrial fibrillation (AF), has limited predictive value. Moreover, transesophageal echocardiography imaging, the gold standard diagnostic method to identify thrombi, is semi-invasive. Consequently, there is a need for alternative and noninvasive diagnostic methods for LAAT risk assessment. MethodsDeep proteomic analysis was conducted in plasma samples from 8 patients with nonvalvular AF, divided into thrombus and control groups (4 patients in each group) based on the presence or absence of LAAT. Biomarkers associated with LAAT were validated using an enzyme-linked immunosorbent assay in a cohort of 179 patients with available clinical, transthoracic, and transesophageal echocardiography data. Predictive models were developed to assess the improvement in LAAT identification. ResultsThe LAAT group had higher CHA2DS2-VASc scores, larger LA diameter, and lower LAA flow velocities. Deep proteomic analysis identified 30 differentially expressed proteins, including myosin light chain 4, prenylcysteine oxidase 1 (PCYOX1), and decorin as potential diagnostic biomarkers of LAAT. The model showed that PCYOX1 and decorin provided an area under the curve (AUC) of 0.970 for LAAT prediction compared with 0.672 in a model including the CHA2DS2-VASc score and LAA cauliflower morphology. The incremental value of proteomic biomarkers for LAAT in patients with nonvalvular AF was further confirmed with the net reclassification improvement and integrated discrimination improvement indices. ConclusionsProtein levels of PCYOX1 and decorin improve the predictive performance for LAAT in patients with nonvalvular AF.

Integrated Bioinformatics-Based Identification and Validation of Neuroinflammation-Related Hub Genes in Primary Open-Angle Glaucoma.

Glaucoma is a leading cause of permanent blindness, affecting 80 million people worldwide. Recent studies have emphasized the importance of neuroinflammation in the early stages of glaucoma, involving immune and glial cells. To investigate this further, we used the GSE27276 dataset from the GEO (Gene Expression Omnibus) database and neuroinflammation genes from the GeneCards database to identify differentially expressed neuroinflammation-related genes associated with primary open-angle glaucoma (POAG). Subsequently, these genes were submitted to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes for pathway enrichment analyses. Hub genes were picked out through protein-protein interaction networks and further validated using the external datasets (GSE13534 and GSE9944) and real-time PCR analysis. The gene-miRNA regulatory network, receiver operating characteristic (ROC) curve, genome-wide association study (GWAS), and regional expression analysis were performed to further validate the involvement of hub genes in glaucoma. A total of 179 differentially expressed genes were identified, comprising 60 upregulated and 119 downregulated genes. Among them, 18 differentially expressed neuroinflammation-related genes were found to overlap between the differentially expressed genes and neuroinflammation-related genes, with six genes (SERPINA3, LCN2, MMP3, S100A9, IL1RN, and HP) identified as potential hub genes. These genes were related to the IL-17 signaling pathway and tyrosine metabolism. The gene-miRNA regulatory network showed that these hub genes were regulated by 118 miRNAs. Notably, GWAS data analysis successfully identified significant single nucleotide polymorphisms (SNPs) corresponding to these six hub genes. ROC curve analysis indicated that our genes showed significant accuracy in POAG. The expression of these genes was further confirmed in microglia, Müller cells, astrocytes, and retinal ganglion cells in the Spectacle database. Moreover, three hub genes, SERPINA3, IL1R1, and LCN2, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the OGD/R-induced glaucoma model. This study suggests that the identified hub genes may influence the development of POAG by regulation of neuroinflammation, and it may offer novel insights into the management of POAG.