Potential Diagnostic Biomarkers Research Articles

TMEM158, as plasma cfRNA marker, promotes proliferation and doxorubicin resistance in ovarian cancer.

The current study aimed to identify the potential biomarker for the diagnosis of ovarian cancer within plasma cell-free RNA (cfRNA) species and to characterize their oncogenic properties. cfRNAs were isolated from the peripheral blood of ovarian cancer patients and sequenced using an NGS platform. Principal component analysis (PCA) was performed using Salmon software. Gene ontology (GO) analysis was conducted with clusterProfiler. The relative abundance of TMEM158 transcripts was determined by real-time PCR. Cell viability and proliferation was monitored using the MTT and cell counting assays, respectively. The protein levels of TMEM158 and ABCG2 were quantified by immunoblotting. We observed a clear separation of cfRNAs between ovarian cancer patients and healthy individuals. Additionally, we identified TMEM158 as the most significantly differential gene in both peripheral blood and tumor tissues. Overexpression of TMEM158 stimulated cell viability and promoted cell proliferation in ovarian cancer cells. Notably, the aberrant upregulation of TMEM158 was closely associated with doxorubicin resistance in ovarian cancer. Mechanistically, we demonstrated that TMEM158 positively regulates ABCG2 expression, which consequently contributes to drug resistance. In summary, we identified cfRNA TMEM158 as a potential diagnostic biomarker for ovarian cancer and elucidated the critical involvement of TMEM158-ABCG2 signaling axis in the development of doxorubicin resistance.

Abstract 4141437: Identification of Mitochondrial-related Diagnostic Biomarkers of Acute Type A Aortic Dissection and Pan-Cancer Analysis

Background: Acute Type A Aortic Dissection (ATAAD) is a lethal disease with limited predictability globally. Cancer, a severe public health issue worldwide, has now become the second leading cause of death in America. In this study, we aimed to explore potential common mechanisms and therapeutic targets between ATAAD and cancer. Aims: Identify mitochondrial-related diagnostic biomarkers of ATAAD and their roles in various cancers. Methods: ATAAD-related datasets GSE52093, GSE98770, GSE190635 were downloaded from GEO and merged after removing batch effects. We verified 119 mitochondrial-related differentially expressed genes (DEGs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Using five machine learning methods (LASSO, SVM, Decision Tree, Random Forest, and Boruta algorithm), we identified two mitochondrial-related diagnostic biomarkers of ATAAD: PPIF and CASQ1. The diagnostic accuracy was performed using receiver operating characteristic (ROC) curves. RT-qPCR was used to detect PPIF and CASQ1 expression. Immune infiltration analysis suggested that PPIF may play a key role in tumor immune microenvironment. We utilized TCGA and GTEx databases, Kaplan-Meier analyses and Cox regression analyses to assess PPIF expression and survival analysis in 33 cancer types. qPCR and Western Blot (WB) assays verified PPIF overexpression in lung adenocarcinoma (LUAD) and uterine corpus endometrial carcinoma (UCEC). CCK-8, wound-healing and transwell assays further verified PPIF’s proliferative, migratory and invasive abilities in LUAD and UCEC. Results: Our study identified PPIF and CASQ1 as hub mitochondrial-related diagnostic biomarkers of ATAAD. Besides its close association with tumor immune infiltration, PPIF also overexpressed in multiple cancer types. Survival analysis suggested the prognostic value of PPIF in most cancers. Experimental results further verified that PPIF promotes the proliferation, migration, and invasion of LUAD and UCEC. Conclusions: PPIF and CASQ1 are potential mitochondrial-related diagnostic biomarkers of ATAAD, not previously reported. Pan-cancer analysis implies that PPIF may serve as a key prognostic and therapeutic target in multiple cancers. PPIF may act as a hub gene linking ATAAD and cancer, offering new insights to reduce ATAAD incidence in cancer patients.

Morphological and Optical Profiling of Melanocytes and SK-MEL-28 Melanoma Cells Via Digital Holographic Microscopy and Quantitative Phase Imaging.

Melanoma, which originates from pigment-producing melanocytes, is an aggressive and deadly skin cancer. Despite extensive research, its mechanisms of progression and metastasis remain unclear. This study uses quantitative phase imaging via digital holographic microscopy, Principal Component Analysis (PCA), and t-distributed Stochastic Neighbor Embedding (t-SNE) to identify the morphological, optical, and behavioral differences between normal melanocytes and SK-MEL-28 melanoma cells. Our findings reveal significant differences in cell shape, size, and internal organization, with SK-MEL-28 cells displaying greater size variability, more polygonal shapes, and higher optical thickness. Phase shift parameters and surface roughness analyses underscore melanoma cells' uniform and predictable textures. Violin plots highlight the dynamic and varied migration of SK-MEL-28 cells, contrasting with the localized movement of melanocytes. Hierarchical clustering of correlation matrices provides further insights into complex morphological and optical relationships. Integrating label-free imaging with robust analytical methods enhances understanding of melanoma's aggressive behavior, supporting targeted therapies and highlighting potential biomarkers for precise melanoma diagnostics and treatment.

Diagnostic value of TRIM22 in diabetic kidney disease and its mechanism.

Diabetic kidney disease (DKD) is the primary reason of chronic kidney disease. Our objective was to discover potential autophagy-related biomarkers of tubulointerstitial injury in DKD and assess their clinical value. We retrieved four datasets (GSE104954, GSE30122, GSE30529, and GSE99340) of renal tubule samples from Gene Expression Omnibus (GEO) and used two algorithms (LASSO and SVM-RFE) to screen for autophagy-related differentially expressed genes (ARDEGs) in DKD. Tripartite motif containing 22 (TRIM22) was identified for subsequent validation. Validation of TRIM22 and autophagic indicators expression in clinical samples and HK-2 cells stimulated by high glucose using immunohistochemistry, immunofluorescence, and western blot. We identified four ARDEGs (TRIM22, PLK2, HTR2B, and FAS) using a diagnostic gene model. ROC curves further confirmed that TRIM22 had the best diagnostic efficacy for DKD. Both clinical samples and HK-2 cells stimulated by high glucose showed high protein expression of TRIM22. The correlation analysis revealed that TRIM22 correlates with SQSTM1, NGAL, and some clinical and pathological indicators in patients with DKD. We identified TRIM22 as a potential diagnostic biomarker for DKD, revealing its high diagnostic value in patients with DKD with moderate-to-severe interstitial fibrosis and tubular atrophy (IFTA). TRIM22 is involved in tubulointerstitial injury and autophagy dysregulation in DKD.

Identification of coagulation-related genes as potential diagnostic biomarkers for pediatric septic shock

This study aimed to identify important clotting associated genes (CRGs) associated with septic shock in children and explore possible important mechanisms of the disease. Five hub genes with diagnostic performance were identified using GEO database and data from literature. These hub genes have strong correlation with immune cells. ceRNA network was constructed to explore potential pathogenic mechanisms. Ten candidate small molecule compounds were identified. In summary, the hub genes may play an important role in the immunity and disease development of septic shock, providing new ideas and strategies for future diagnosis and mechanism evaluation of children with septic shock.

β-Hydroxybutyrate and Citrate Synthase as Potential Diagnostic Biomarkers in Aging-Related Atrial Fibrillation.

The incidence of atrial fibrillation (AF) increases with age; however, the precise mechanisms by which aging elevates AF risk and the effective biomarkers for managing AF in elderly patients remain unclear. We analyzed plasma samples from 100 elderly AF patients, 100 young and 100 elderly patients without atrial fibrillation (NAF), along with left atrial tissues obtained from both AF and NAF patients following valve replacement. Our findings indicate reduced levels of β-OHB and citrate synthase (CS) activity in elderly AF patients compared to their NAF counterparts. Statistical analysis revealed a protective association between β-OHB and CS activity concerning the occurrence of elderly AF. Furthermore, atrial tissues from elderly AF patients exhibited mitochondrial dysfunction, structural remodeling, and low-voltage areas. These results suggest that dysregulation of β-OHB levels and CS activity may contribute to aging-related AF by affecting mitochondrial function and atrial remodeling, highlighting their potential as diagnostic biomarkers for this condition.

Genome-wide DNA methylation profiling reveals a novel hypermethylated biomarker PRKCB in gastric cancer

Globally, gastric cancer (GC) ranks among the most prevalent forms of malignancy, posing a significant health burden. Epigenetic modifications, predominantly characterized by alterations in DNA methylation patterns, have been linked to a diverse array of neoplastic processes. Here, we undertake a comprehensive analysis of the DNA methylation signature in GC, with the aim to discover the potential diagnostic epigenetic biomarkers. Utilizing the Illumina 935 K BeadChip, we conducted a genome-wide exploration of DNA methylation patterns in four paired samples of GC tissues and adjacent non-cancerous counterparts. The bisulfite-pyrosequencing (n = 7) was employed to the quantification for methylated gene. The pubic databases including GWAS Catalog, TCGA and GEO were used. The immunohistochemistry and qRT-PCR analysis were performed. In contrast to adjacent tissues, GC tissues manifested pronounced hypermethylation patterns specifically within the promoter cytosine-phosphate-guanine (CpG) islands, indicating localized epigenetic alterations. DNA methylome analysis further revealed 4432 differentially-methylated probes (DMPs), with the gene PRKCB exhibited the most prominent average DNA methylation disparity (mean Δβ = 0.353). Pyrosequencing validation confirmed three DMPs within the PRKCB promoter (cg08406370, cg00735962, and cg18526361). Notably, the mean methylation levels of PRKCB were inversely correlated with mRNA expression levels in the GWAS Catalog. Furthermore, both mRNA and protein expression levels of PRKCB were significantly reduced in GCs when compared to their adjacent non-cancerous counterparts, verified by TCGA and GEO database. Our study reveals significant DNA methylation alterations in GC and emphasizes the pivotal role of PRKCB gene hypermethylation in conferring GC risk, which offers fresh perspectives for advancing diagnostic approaches and therapeutic strategies for GC.

Integrative Analyses of Genes of Pediatric Non-alcoholic Fatty Liver Disease Associated with Energy Metabolism.

Pediatric non-alcoholic fatty liver disease (NAFLD) is a chronic steatosis of the liver associated with energy metabolism in children and adolescents, failure to intervene promptly can elevate the risk of developing hepatocellular carcinoma. Therefore, this study aimed to understand the underlying mechanism of pediatric NAFLD and investigate potential biomarkers and therapeutic targets. We investigated genes using the GSE185051 data set related to energy metabolism from the GeneCards database, constructed protein-protein interaction network, identified hub genes and established networks representing interactions between these hub genes and miRNA, RNA-binding proteins, transcription factors, and drugs. Subsequently, we performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis, Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis. Our analysis identified 9 hub genes through the PPI network. The target molecules were identified through the interaction network between hub genes and miRNAs, RNA-binding proteins, transcription factors, and drugs. GO analysis revealed that hub genes were associated with oxidative stress responses and other pathways. KEGG analysis highlighted their involvement in pathways such as insulin resistance, among others. GSEA revealed that hub genes were highly enriched in pathways related to Omega-9 fatty acid synthesis, among others. Immune infiltration analysis suggested that mast cells and T follicular helper cells play significant roles in the pathogenesis of NAFLD. We identified the hub genes in pediatric NAFLD closely related to energy metabolism. These findings offer the potential for identifying potential novel diagnostic biomarkers, and establishing therapeutic targets for pediatric NAFLD.

Metabolomic profiling of human feces and plasma from extrauterine growth restriction infants.

Extrauterine growth restriction (EUGR) affects a substantial proportion of preterm infants and may influence both short-term complications and long-term sequelae. While many preterm infants with EUGR are secondary to small for gestational age (SGA) or very low birth weight (VLBW), a subset of EUGR infants do not exhibit these conditions. The purpose of this study is to investigate the metabolic profiles and biomarkers of EUGR infants in the absence of SGA and VLBW. A total of 100 feces (n = 50) and plasma samples (n = 50) were collected from participants categorized as either EUGR (EUGR group) or non-EUGR (NonEUGR group) in the absence of SGA and VLBW. Metabolites were characterized via UPLC-MS/MS using the Discovery HD4® platform. Data normalization, partial least squares discriminant analysis (PLSDA), and KEGG enrichment analysis of metabolite profiles were performed using the MetaboAnalyst 6.0. The clinical characteristics of preterm infants differed significantly between the EUGR and NonEUGR groups at discharge, including length of stay, weight Z-score, weight, height Z-score, height, head circumference, and fat-free mass. The PLSDA model exhibited clustering within groups and separation between groups. A total of 58 and 71 differential metabolites were identified in feces and plasma samples, respectively. They were involved in pathways such as caffeine, galactose, glutathione, cysteine, and methionine metabolisms. In the feces sample, 1-palmitoyl-galactosylglycerol exhibited a significant negative correlation with the growth characteristics of preterm infants, while 1-palmitoyl-2-palmitoleoyl-GPC displayed the opposite pattern. In plasma samples, androsterone glucuronide displayed a significant positive correlation with the growth characteristics of preterm infants, whereas 2-methoxyhydroquinone sulfate generated an opposite pattern. Moreover, 2-oleoylglycerol and sphinganine-1-phosphate exhibited the highest area under the curve in feces and plasma samples, respectively, according to diagnostic ROC curves. Preterm infants with EUGR, in the absence of SGA and VLBW, exhibit specific clinical characteristics and metabolomic profiles. Sphinganine-1-phosphate and 2-oleoylglycerol may hold promise as diagnostic markers for EUGR in the absence of SGA and VLBW. The objective of this study is to identify the differential metabolites in preterm infants with extrauterine growth restriction (EUGR) in the absence of small for gestational age (SGA) or very low birth weight (VLBW). Preterm infants with EUGR without SGA and VLBW exhibit specific clinical characteristics and metabolomic profiles. Sphinganine-1-phosphate and 2-oleoylglycerol emerged as potential diagnostic biomarkers for EUGR. This study enhances our understanding of the metabolomic profile in preterm infants with EUGR without SGA or VLBW. Our findings will offer valuable evidence for improving nutritional management and shedding light on the associated pathophysiological mechanisms of EUGR.

Plasma COL10A1 Level, a Potential Diagnostic and Prognostic Biomarker for Pancreatic Ductal Adenocarcinoma.

COL10A1 expression was up-regulated and could promote tumor development in pancreatic cancer. As a secreted protein, plasma COL10A1 level was proven to have certain diagnostic efficacy in gastric cancer, breast cancer, and colorectal cancer. It is still unknown whether it has a biomarker role for pancreatic cancer. To explore and analyze the diagnostic and prognostic value of plasma COL10A1 level in pancreatic ductal adenocarcinoma (PDAC). The RNA-seq dataset of PDAC from The Cancer Genome Atlas (TCGA) and six expression profiling microarray datasets from Gene Expression Omnibus (GEO) were downloaded to analyze the expression of COL10A1 in tissues. Thirty-six patients with PDAC and eighteen healthy volunteers were enrolled to measure COL10A1 levels in tissues and plasmas, and the relationship between clinical characteristics and the COL10A1 levels was analyzed. The diagnostic and prognostic efficacy of plasma COL10A1 levels were calculated. Aspects of COL10A1 expression level in tissues, COL10A1 expression was significantly higher in PDAC tissue than adjacent normal tissue. The expression of COL10A1 was correlated with T, M, and AJCC stages. Patients with high COL10A1 expression had worse recurrence-free survival (RFS) and overall survival (OS) than those with low expression. Aspects of COL10A1 expression levels in plasma, its diagnostic area under the curve (AUC) for PDAC was 0.926 (95% CI 0.853-0.999), diagnostic sensitivity was 81% (95% CI 64-92%), and specificity was 100% (95% CI 81-100%). The time-dependent AUCs at 1-year and 3-year were 0.71 (95% CI 0.51-0.90) and 0.74 (95% CI 0.48-1.00), respectively. In PDAC, plasma COL10A1 levels showed certain diagnostic and prognostic efficacy. COL10A1 may be a diagnostic and prognostic biomarker for PDAC and play a role in liquid biopsy of this disease.

Characterization of Immune-Related circRNAs and mRNAs in Human Chronic Atrophic Gastritis.

Chronic atrophic gastritis (CAG) is a severe condition characterized by inflammation and loss of appropriate mucosal glands in the stomach. The underlying mechanisms of CAG development remain unclear. Exploring immune-related circular RNAs (circRNAs) could provide insights for potential diagnostic and therapeutic strategies. Samples from 40 patients with CAG and non-CAG (CNAG) underwent high-throughput sequencing, and EdgeR analysis identified differentially expressed circRNAs and mRNAs. Gene Ontology (GO) analysis elucidated biological functions, while Immune Cell Abundance Identifier (ImmuCellAI) estimated immune cell abundance. Flow cytometry analyzed immune cell infiltration. Weighted gene co-expression network analysis (WGCNA) identified hub genes related to the immune response in CAG. CircRNA-mRNA networks were constructed, and qRT-PCR validated findings. A total of 163 differentially expressed immune-related genes (DEIRGs) were identified between CAG and CNAG. The upregulated immune-related mRNAs in CAG were significantly enriched in antimicrobial humoral response, viral entry into host cells, neutrophil activation, and leukocyte migration. Conversely, downregulated immune-related mRNAs were linked to regulation of natural killer cell-mediated cytotoxicity, positive regulation of adaptive immune response, antigen receptor-mediated signaling pathway, and B cell activation. Immune Cell Abundance Identifier (ImmuCellAI) and flow cytometry confirmed increased neutrophil infiltration in CAG compared to CNAG. WGCNA identified 56hub immune-related genes. Additionally, circRNA expression profiles in CNAG and CAG were explored, with 19 upregulated and 23 downregulated circRNAs identified in CAG. The upregulated circRNAs were associated with biological processes like carnitine metabolic process and regulation of B cell receptor signaling pathway. A circRNA-mRNA co-expression network was constructed based on five circRNAs highly related to hub immune-related genes. Furthermore, the expression of eight immune-related mRNAs and five circRNAs were validated in CAG. This study is the first systematic analysis of circRNA profiles in CAG and provide important insights for potential immunotherapeutic strategies and early diagnostic biomarkers in CAG treatment.

Altered intestinal microbiota and fecal metabolites in patients with latent and active pulmonary tuberculosis.

Pulmonary tuberculosis (PTB) is the main cause of infection-related mortality and the most common infectious disease that develops resistance to antibiotics. Gut microbiota and their associated metabolites are assumed to induce and influence the development of PTB. However, the alterations of gut microbiota and metabolites in TB patients is currently unclear. Fecal samples were collected from 13 PTB patients, 13 LTBI patients, and 13 healthy controls (HC). 16S rRNA sequencing and metabolomics were used to analyze the changes in the intestinal microbiota and the composition of fecal metabolites in groups. Our findings indicated that the α-diversity of the gut microbiota in patients with PTB and LTBI decreases compared to HC, and at the phylum level, the relative abundance of Firmicutes decreases and the relative abundance of Bacteroides increases. And six genera were notably enriched in PTB patients and four in LTBI patients. Metabolomic analysis showed alterations in metabolite levels, such as short-chain fatty acids and amino acids. we comprehensively explored the changes in the gut microbes and fecal metabolites in patients with PTB and LTBI from the perspective of the gut microbiota, which may provide potential diagnostic biomarkers and therapeutic targets for TB diagnosis and treatment.

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in Crohn’s disease by integrating bioinformatics and machine learning

Crohn’s disease (CD) presents significant diagnostic and therapeutic challenges due to its unclear etiology, frequent relapses, and limited treatment options. Traditional monitoring often relies on invasive and costly gastrointestinal procedures. This study aimed to identify specific diagnostic markers for CD using advanced computational approaches. Four gene expression datasets from the Gene Expression Omnibus (GEO) were analyzed, identifying differentially expressed genes (DEGs) through gene set enrichment analysis in R. Key biomarkers were selected using machine learning algorithms, including LASSO logistic regression, SVM‑RFE, and Random Forest, and their accuracy was assessed using receiver operating characteristic (ROC) curves and nomogram models. Immune cell infiltration was analyzed using the CIBERSORT algorithm, which helped reveal associations between diagnostic markers and immune cell patterns in CD. From a training set of 605 CD samples and 82 normal controls, we identified eight significant biomarkers: LCN2, FOLH1, CXCL1, FPR1, S100P, IGFBP5, CHP2, and AQP9. The diagnostic model showed high predictive power (AUC=0.954) and performed well in external validation (AUC = 1). Immune cell infiltration analysis highlighted various immune cells involved in CD, with all diagnostic markers strongly linked to immune cell interactions. Our findings propose candidate hub genes and present a nomogram for CD diagnosis, providing potential diagnostic biomarkers for clinical applications in CD.

Study on the changes and significance of CXCL10 level in serum of isolated polymyalgia rheumatica.

To investigate the significance of CXC chemokine ligand 10 (CXCL10) in the pathogenesis of isolated polymyalgia rheumatica (PMR). The serum of six PMR patients diagnosed and treated at the First Affiliated Hospital of Wannan Medical College from September 2019 to December 2020 before treatment and after remission was collected, and the serum of six active rheumatoid arthritis (RA) patients and six healthy medical checkups were also collected, and protein microarray technology was used to detect 24 cytokines, including IL-6, IL-4, CXCL10, CXCL8, and CXCL2. Subsequently, serum was collected from other 28 patients with active PMR, 26 patients with PMR in remission, 24 patients with active RA, and 24 healthy medical checkups who were diagnosed and treated at the First Affiliated Hospital of Wannan Medical College from January 2021 to July 2023, and the enzyme-linked immunosorbent assay (ELISA) was used to validate and compare the levels of CXCL10 in each group and analyze the correlation between the levels of serum CXCL10 and the parameters of the clinical activities of PMR. Protein microarray screening revealed significant differences in CXCL10 before and after PMR treatment, and ELISA validation revealed that peripheral serum CXCL10 levels were significantly higher in the PMR-active group than in the remission group (P < 0.001), and also significantly higher than in the RA-active group (P = 0.003) and in the healthy control group (P < 0.001); correlation analysis showed a significant positive correlation between serum CXCL10 levels and serum ferritin in PMR patients (r = 0.450, P = 0.024). In the ROC curve for distinguishing PMR and RA, the area under the curve is 0.741, sensitivity = 0.643, and specificity = 0.792. CXCL10 may play a role in the pathogenesis of isolated PMR and its level might contribute to the differential diagnosis of PMR and RA. Key Points •The concentration of CXCL10 was higher in peripheral blood of isolated PMR patients. •CXCL10 is a potential diagnostic biomarker for isolated PMR patients. •The level of CXCL10 might contribute to the differential diagnosis of PMR and RA.

FABP7: A Potential Diagnostic and Prognostic Biomarker for Clear Cell Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is highly heterogeneous, with distinct patient management between clear cell RCC (ccRCC) and non-ccRCC groups. Previous bioinformatics and machine learning techniques identified fatty acid binding protein 7 (FABP7) as a potential ccRCC biomarker. However, FABP7 expression studies between ccRCC and non-ccRCC were incomplete. This study aimed to assess FABP7 as a biomarker for distinguishing between ccRCC and non-ccRCC tissue samples. FABP7 expression was evaluated via immunohistochemical staining in 58 RCC cases, including 43 ccRCC and 15 non-ccRCC cases. Staining results were interpreted using H-scores; scores above the cut-off were deemed positive. The correlation between FABP7 expression and clinicopathological RCC features was investigated. FABP7 positivity was 48.8% in ccRCC and only 13.3% in non-ccRCC cases, with weak positivity in non-ccRCC tissues. FABP7 expression significantly differed between ccRCC and non-ccRCC (p<0.05). This finding was confirmed in a TCGA dataset. However, FABP7 expression was not correlated with other RCC clinicopathological features in our dataset. TCGA results linked FABP7 expression to tumor stage and disease-free survival in patients with ccRCC. This study preliminarily evaluated FABP7 as a differential diagnostic biomarker in RCC subtyping, showing higher expression in ccRCC than non-ccRCC. FABP7 may serve as a potential diagnostic and prognostic biomarker for ccRCC.

Epithelial membrane protein 1 in human cancer: a potential diagnostic biomarker and therapeutic target.

Epithelial membrane protein 1 (EMP1) is a member of the small hydrophobic membrane protein subfamily. EMP1 is aberrantly expressed in various tumor tissues and governs multiple cellular behaviors (e.g., proliferation, differentiation, and migration). The resultant regulation of the cancer pathway is responsible for the metastasis of cancer cells and determines the risk of malignant tumor progression. This review provides an updated overview of EMP1 as either an oncogene or a tumor suppressor contingent on the cancer type and summarizes its upstream regulators and downstream target genes. This systematic review summarizes our current understanding of the role of EMP1 in malignant tumor development, including critical functional mechanisms and implications for its potential use as the biomarker and therapeutic target.

MicroRNA-Targeted Gene Regulation in Salivary Gland Tissue of De Novo Parkinson's Disease Patients.

Although α-synucleinopathy has been confirmed in the submandibular gland (SMG) tissue of Parkinson's disease (PD) patients, in-depth disease-related molecular research, such as tissue-specific transcriptional signals, has not been performed. In the present study, disease-relevant tissue-specific transcriptional signals in SMG tissue from PD patients were investigated to identify potential diagnostic, prognostic, and pathophysiologic biomarkers. Here, seven de novo drug-naïve PD patients and six age- and sex-matched individuals without neurological or psychological diseases were enrolled. Total RNA sequencing (RNA-seq) and total small RNA-seq (smRNA-seq) were performed on SMG tissue and blood samples, with 26 RNA-seq and 26 smRNA-seq samples used for the final analysis. Differentially expressed genes (DEGs) and microRNAs in SMG tissue and blood from PD patients were obtained and their functional integration and interaction network were analyzed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs interacted with cytokine-, inflammation-, and immune-related pathways. Synphilin-1 expression was significantly downregulated in SMG tissue of PD patients, and α-synuclein expression did not significantly differ between PD patients and controls in either SMG tissue or blood. Fifteen tissue-specific miRNA signals in SMG tissue were identified that showed better diagnostic ability compared with those in blood samples. The correlation between DEGs and environmental factors appeared altered in PD patients. The results indicated the DEGs and microRNA signatures identified in SMG tissue may be promising diagnostic and prognostic biomarkers. These molecular insights offer potential avenues for the development of novel therapeutic strategies targeting the underlying disease mechanisms in PD patients.

Proteomic profiling of extracellular vesicles in takotsubo syndrome

Abstract Background/Purpose Takotsubo syndrome (TS) is an acute form of heart failure characterized by transient regional wall motion abnormalities triggered by a stressful event. The mechanisms underlying its development and recovery are poorly understood, resulting in a lack of disease-specific treatments and diagnostic markers. Extracellular vesicles (EVs) play a significant role in cellular communication and have been shown to be important in various diseases. Their involvement in cardiac conditions like TS is an emerging area of research. The primary objective of this study is to isolate and characterize EVs, as well as profile their proteomic profile, from the heart tissue of rats induced with TS. Methods Rats underwent TS induction through the infusion of 1 mg/kg isoprenaline over 15 minutes (TS24h), or were given saline (control). High-resolution echocardiography verified apical ballooning at 6 hours. After 24 hours, heart tissues from apical and basal segments were collected and processed. EV isolation involved tissue slicing, enzymatic digestion, and differential centrifugation steps, including a final iodixanol cushion separation for large and small EVs (Figure 1). Tandem mass tags and mass spectrometry were utilized for global proteomics and any differentially expressed proteins (DEPs) were identified. Analytical techniques such as volcano plots, heatmaps, enrichment analysis, and protein clustering/networks were employed. The strongest clusters (lowest False Discovery Rate and highest intensity) were selected, and their Gene Ontology (GO) terms/pathways were identified. Results Pure, cup-shaped, vesicles ranging from 50-800nm were successfully isolated (figure 1). EVs from apex of control and TS24h hearts had lower protein concentrations compared to their corresponding basal segments. Global proteomic analysis revealed a distinct protein profile in EVs from the apical segment of TS hearts at 24 hours. A total of 256 (TS24h-apex vs control-apex) and 561 proteins (TS24h-apex vs TS24h-base) were differentially expressed. No DEPs were observed when comparing the basal segments of TS24h and control hearts. Functional enrichment analysis of the DEPs showed an abundant change of biological processes related to metabolic lipid processes, inflammatory response, complement activation, reorganization of extracellular matrix. A downregulation was seen for biological processes related to mitochondrial ATP synthesis coupled electron transport and muscle contraction. Conclusion This study demonstrates a distinct EV protein profile in the apical segments of TS hearts, with marked changes in proteins related to metabolic lipid processes, inflammation, and mitochondrial activity. This extensive catalogue of novel proteins sets the stage for future research aimed at identifying potential therapeutic targets and diagnostic biomarkers, and enabling proof-of-concept studies in TS.

Molecular Genetic Factors of Risk Stratification of Lymph Node Metastasis in Endometrial Carcinoma.

According to epidemiological studies, endometrial carcinoma is one of the most frequently diagnosed malignancies of the female reproductive system, with an increasing incidence. Currently, the risk stratification of this neoplasm takes into account the stage, degree of tumor differentiation, histological type and depth of myometrial invasion. Since the publication of the last International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer in 2009, numerous reports have appeared on the molecular characteristics of different types of endometrial carcinoma. Taking this into account, the FIGO Committee determined in 2023 that changes and updates to the staging system are justified to reflect new information about this tumor. Due to the high prevalence of the disease and mortality from endometrial cancer, an in-depth study of the molecular genetic characteristics of tumor cells is relevant; the results of such studies can be used to improve the efficiency of diagnosis, assess the risk of metastasis and prognosis of the disease. Lymph node assessment is crucial for the choice of treatment strategy for endometrial cancer, since metastatic lymph node involvement is one of the main factors affecting prognosis. At the same time, the criteria for the appropriateness of lymphadenectomy in low-differentiated malignant tumors are not clearly defined. Various molecular methods have been proposed to assess the status of lymph nodes; candidate genes are being studied as potential diagnostic biomarkers, as well as microRNA. The aim of the study was to analyze the literature data on numerous studies of molecular risk factors for progression in endometrioid carcinoma, as well as to preserve the most important marker changes in relation to the prognostic development of this disease. A literature review was conducted using data from the electronic databases PubMed, Google Scholar, and Wiley Cochrane Library for the period from 2018 to 2023 using the specific keywords. The current scientific genetic studies on metastasis and prognostic factors in uterine cancer were analyzed, and a systematization of the reviewed data from the modern literature was done. To select the most effective treatment - intraoperative, adjuvant or combination therapy, minimize postoperative risks of lymphadenectomy and clearly predict the results - further study of the molecular genetic features of endometrial cancer is necessary.

Oral, Vaginal, and Stool Microbial Signatures in Patients With Endometriosis as Potential Diagnostic Non-Invasive Biomarkers: A Prospective Cohort Study.

To identify a microbial signature for endometriosis for use as a diagnostic non-invasive biomarker. Prospective cohort pilot study. Nepean Hospital and UNSW Microbiome Research Centre, Australia. Sixty-four age- and sex-matched subjects (n = 19 healthy control (HC); n = 24 non-endometriosis (N-ENDO) and n = 21 confirmed endometriosis (ENDO)). All study participants, besides healthy controls, underwent laparoscopic surgical assessment for endometriosis, and histology was performed on excised lesions. Oral, stool and, vaginal samples were self-collected at a single time point for healthy controls, and preoperatively for patients undergoing laparoscopy. Samples underwent 16S rRNA amplicon sequencing, followed by bioinformatics analysis. Compositional differences between cohorts as identified by diversity analyses, and differentially abundant microbial taxa, as identified by LEfSE analysis. The composition of the oral (adjusted p = 0.003), and stool (adjusted p = 0.042) microbiota is different between the three cohorts. Differentially abundant taxa are present within each cohort as identified by LEfSE analysis. Particularly, Fusobacterium was enriched in the oral samples of patients with moderate/severe endometriosis. Taxonomic and compositional differences were found between the microbiota in the mouth, gut and, vagina of patients with and without endometriosis and healthy controls. Fusobacterium was enriched in patients with moderate/severe endometriosis. Fusobacterium is noted as a key pathogen in periodontal disease, a common comorbidity in endometriosis. These findings suggest a role for the oral, stool and, vaginal microbiome in endometriosis, and present potential for microbial-based treatments and the design of a diagnostic swab.