Potential Non-invasive Biomarkers Research Articles

Diagnostic accuracy of an uncorrected native T1 mapping sequence for liver fibrosis and inflammation in autoimmune hepatitis: a prospective study using histopathology as reference standard.

There is an unmet clinical need for non-invasive imaging biomarkers that could replace liver biopsy in the management of patients with autoimmune hepatitis (AIH). In this study, we sought to evaluate the diagnostic accuracy of a simple uncorrected, non-contrast T1 mapping for detecting fibrosis and inflammation in AIH patients using histopathology as a reference standard. Over 3years, 33 patients with AIH were prospectively studied using a multiparametric liver MRI protocol which included T1 mapping. Biopsies were performed up to 3months before imaging, and a standardized histopathological score for fibrosis (F0-F4) and inflammatory activity (PPA0-4) was used as a reference. Statistical analysis included independent t test, Mann-Whitney U-test, and ROC (receiver operating characteristic) analysis. T1 mapping values were significantly higher in patients with advanced fibrosis (F0-2 vs. F3-4; p < 0.015), significant fibrosis (F0-1 vs. F2-4; p < 0.005), and significant inflammatory activity (PPA 0-1 vs. PPA 2-4 p = 0.048). Moreover, the technique demonstrated a good diagnostic performance in detecting significant (AUC 0.856) and advanced fibrosis (AUC 0.835), as well as significant inflammatory activity (AUC 0.763). A rapid, simple, uncorrected, non-contrast T1 mapping sequence showed satisfactory diagnostic performance in comparison with histopathology for detecting significant tissue inflammation and fibrosis in AIH patients, being a potential non-invasive imaging biomarker for monitoring disease activity in such individuals.

Optical Coherence Tomography Angiography Retinal Imaging Associations With Burden of Small Vessel Disease and Amyloid Positivity in the Brain.

Alzheimer disease (AD) and other dementias are associated with vascular changes and amyloid deposition, which may be reflected as density changes in the retinal capillaries. These changes may can be directly visualized and quantified with optical coherence tomography angiography (OCTA), making OCTA a potential noninvasive preclinical biomarker of small vessel disease and amyloid positivity. Our objective was to investigate the feasibility of retinal imaging metrics as noninvasive biomarkers of small vessel disease and amyloid positivity in the brain. We investigated associations between OCTA and neuroimaging and cognitive metrics in 41 participants without dementia from the Mayo Clinic Study of Aging and Alzheimer's Disease Research Center. OCTA metrics included superficial, deep, and full retina capillary density of the fovea, parafovea, and macula as well as the area of the foveal avascular zone (FAZ). Neuroimaging metrics included a high burden of white matter hyperintensity (WMH), presence of cerebral microbleeds (CMB), lacunar infarcts, and amyloid positivity as evidenced on positron emission tomography (PET), whereas cognitive metrics included mini-mental status examination (MMSE) score. We performed generalized estimating equations to account for measurements in each eye while controlling for age and sex to estimate associations between OCTA metrics and neuroimaging and cognitive scores. Associations between OCTA and neuroimaging metrics were restricted to the fovea. OCTA showed decreased capillary density with high burden of WMH in both the superficial (P = 0.003), deep (P = 0.004), and full retina (P = 0.01) in the fovea but not the parafovea or whole macula. Similarly, participants with amyloid PET positivity had significantly decreased capillary density in the superficial fovea (P = 0.027) and deep fovea (P = 0.03) but higher density in the superficial parafovea (P = 0.038). Participants with amyloid PET positivity also had a significantly larger FAZ (P = 0.031), whereas in those with high WMH burden the difference did not reach statistical significance (P = 0.075). There was also a positive association between MMSE and capillary density of the full retina within the fovea (P = 0.037) and in the superficial parafovea (P = 0.046). No associations were found between OCTA metrics and presence of CMB or presence of lacunar infarcts. The associations of lower foveal capillary density with cerebral WMH and amyloid positivity suggest that further research is warranted to evaluate for shared mechanisms of disease between small vessel disease and AD pathologies.

The metabolites mainly composed of lipids in tongue coating are non-invasive potential biomarkers for chronic gastritis

The changes in tongue coating metabolites in patients with chronic gastritis (CG) under different gastroscopy indicators were analyzed, and these metabolites were screened for potential non-invasive biomarkers to assist in the diagnosis of chronic gastritis. The technology of gas chromatography and liquid chromatography combined with mass spectrometry has been used to more comprehensively detect tongue coating metabolites of 350 CG patients. Spearman correlation analysis and random forest algorithm were used to screen metabolites that can serve as potential biomarkers. Compared with healthy individuals, CG group showed significant changes in the content of 101 metabolites, with an increase in the content of 54 metabolites and a decrease in the content of 47 metabolites. These differential metabolites are mainly composed of 47 lipids and lipid like substances. 1 metabolite was associated with bile reflux, 1 metabolite was associated with gastric mucosal erosion, 10 metabolites were associated with atrophy, 10 metabolites were associated with intestinal metaplasia, and 3 metabolites were associated with Helicobacter pylori infection. The ROC model composed of 5 metabolites can distinguish between CG group and healthy individuals, with an accuracy of 95.4%. The ROC model composed of 5,6-Dihydroxyindole can distinguish between chronic superficial gastritis group and chronic atrophic gastritis group, with an accuracy of 75.3%. The lipids and lipid like metabolites were the main abnormal metabolites in patients with chronic gastritis. It was worth noting that the content of Sphinganine 1-phase, 4-Ipomenol, and Nervonic acid in tongue coating increased, and the content of 1-Methyladenosine and 3-Hydroxycapric acid decreased, which helped to identify CG patients. The decrease in the content of 5,6-dihydroxyindole reminded patients that the development trend of CG was shifting from superficial to atrophic or even intestinal metaplasia. The detection of these metabolic markers of tongue coating was expected to be developed as a non-invasive and convenient technology in the future to assist us in monitoring and diagnosing the occurrence and development of CG.

Expression profile of circulating miRNAs in patients with atrial fibrillation-dominated cardioembolic stroke: A systematic review and bioinformatics analysis

BackgroundCardioembolic stroke is a type of ischemic stroke with high disability and mortality, a high recurrence rate and poor prognosis. miRNAs have been explored as potential noninvasive biomarkers in atrial fibrillation and ischemic stroke, but their expression profile in cardioembolic stroke still needs to be explored. This study will explore the differences in miRNA expression between cardioembolic stroke patients and healthy people through meta-analysis and attempt to analyze the target genes by bioinformatics analysis. MethodsLiterature databases and gene expression databases were searched from the inception date to June 2022. The study reported the circulating miRNA expression profiles in cardioembolic stroke patients and healthy controls. miRNAs with significantly differential expression and their target genes were analyzed. ResultsThree articles and one gene expression dataset were included in the analysis. The results showed that miR-21–5p (SMD: 2.16; 95 % CI: 1.57, 2.75; p < 0.001), miR-943, miR-145–3p, and miR-3148 were upregulated in cardioembolic stroke patients compared with controls. The downregulated miRNAs included miR-3136–5p, miR-2277–5p, and miR-2277–3p. The area under the receiver operating characteristic curve of miR-21–5p for cardioembolic stroke was 0.975 (0.933–0.989). For the enrichment results, the target genes of upregulated miRNAs were enriched in the MAPK signaling pathway, Ras signaling pathway, etc. The target genes of downregulated miRNAs were also enriched in the Ras signaling pathway. ConclusionsThis study suggested that circulating miR-21–5p is upregulated in cardioembolic stroke patients compared to healthy controls. The Ras signaling pathway plays an important role in pathogenesis according to enrichment analysis.

The diagnostic value of serum exosomal SNORD116 and SNORA21 for NSCLC patients.

Non-small cell lung cancer (NSCLC) is a widespread and serious global malignancy. This study aimed to examine the clinical relevance of serum exosomal SNORD116 and SNORA21 as novel diagnostic biomarkers for NSCLC. Serum exosomes from 226 healthy controls and 305 NSCLC patients were isolated by ultracentrifugation. Characterization of exosomes was conducted by qNano, transmission electron microscopy (TEM) and Western immunoblotting. RT-PCR revealed snoRNAs that were differentially expressed. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance. In NSCLC patients, the levels of serum exosomal SNORD116 and SNORA21 were significantly reduced compared to those in healthy controls (P < 0.0001 for both). ROC curves showed AUC values of 0.738 and 0.761. By combining SNORD116 and SNORA21 with traditional blood biomarkers CYFRA21-1 and carcinoembryonic antigen (CEA), the AUC increased to 0.917. Moreover, these two exosomal snoRNAs distinguished between patients with metastatic NSCLC (n = 132) and those with non-metastatic NSCLC (n = 173) significantly (P < 0.0001 for both). The ROC curves gave AUC values of 0.743 and 0.694, respectively. The combined analysis raised the AUC to 0.751. The diagnostic power of these two exosomal snoRNAs combined with CYFRA21-1 and CEA increased to 0.784. This study demonstrated that serum exosomal SNORD116 and SNORA21 can be used as potential promising non-invasive diagnostic biomarkers for NSCLC.

Extraction and characterization of exosomes from the exhaled breath condensate and sputum of lung cancer patients and vulnerable tobacco consumers—potential noninvasive diagnostic biomarker source

Noninvasive sample sources of exosomes, such as exhaled breath and sputum, which are in close proximity to the tumor microenvironment and may contain biomarkers indicative of lung cancer, are far more permissive than invasive sample sources for biomarker screening. Standardized exosome extraction and characterization approaches for low-volume noninvasive samples are critically needed. We isolated and characterized exhaled breath condensate (EBC) and sputum exosomes from healthy nonsmokers (n = 30), tobacco smokers (n = 30), and lung cancer patients (n = 40) and correlated the findings with invasive sample sources. EBC samples were collected by using commercially available R-Tubes. To collect sputum samples the participants were directed to take deep breaths, hold their breath, and cough in a collection container. Dynamic light scattering, nanoparticle tracking analysis, and transmission electron microscopy were used to evaluate the exosome morphology. Protein isolation, western blotting, exosome quantification via EXOCET, and Fourier transform infrared spectroscopy were performed for molecular characterization. Exosomes were successfully isolated from EBC and sputum samples, and their yields were adequate and sufficiently pure for subsequent downstream processing and characterization. The exosomes were confirmed based on their size, shape, and surface marker expression. Remarkably, cancer exosomes were the largest in size not only in the plasma subgroups, but also in the EBC (p < 0.05) and sputum (p = 0.0036) subgroups, according to our findings. A significant difference in exosome concentrations were observed between the control sub-groups (p < 0.05). Our research confirmed that exosomes can be extracted from noninvasive sources, such as EBC and sputum, to investigate lung cancer diagnostic biomarkers for research, clinical, and early detection in smokers.

P-040 The characteristic of human seminal plasma extracellular vesicle (SPEVs) profiles with different sperm features in a large cohort of 309 Taiwanese men

Abstract Study question To investigate human seminal plasma extracellular vesicle profiles in different sperm characteristics and their potential clinical application. Summary answer Normozoospermic semen has significantly higher SPEV concentration than asthenozoospermic or oligozoospermic samples. Moreover, SPEV concentration was highly correlated with total motile sperm count. What is known already Seminal plasma extracellular vesicles (SPEVs) are cell-derived membrane structures that carry proteins, nucleic acid, and lipids, which can modify the constitution and biological function of sperm. However, the characteristics of SPEVs in different sperm features remained unclear. Study design, size, duration From January 2021 to September 2023, 309 men who visited the NCKUH andrology clinic agreed to collect semen samples for this study, which the Institutional Review Board has approved. Participants/materials, setting, methods Semen parameters were measured by the X1 CASA system (Bonraybio, Taiwan). SPEVs were isolated by size exclusion chromatography column and ExoQuick™. Next, the SPEVs’ concentration and size distribution were performed with nanoparticle tracking analysis. The Kruskal-Wallis test calculated comparison in multiple groups, and Dunn’s multiple comparison tests accessed group-group comparison. The Pearson correlation coefficient r of exosome concentration with individual sperm parameters was calculated. A p-value less than 0.05 was set as statistical significance. Main results and the role of chance Among them, 59 semen samples were presented with normozoospermia, 36 were oligozoospermia, 73 were asthenozoospermia, and 141 samples had no sperm in semen. Among these 141 azoospermic men, 89 men are characterized by non-obstructive azoospermia (NOA), while the other 52 men had a vasectomy. Our data showed that normozoospermic semen has significantly higher SPEV concentration than asthenozoospermic or oligozoospermic semen samples (26 x109 [IQR 17.25 x109-56.25 x109] versus 12 x109 [IQR 5.6 x109-19.5 x109] versus 15.5 x109 [IQR 8.575 x109-26.75 x109], p = 0.0001). Nevertheless, azoospermic semen has the lowest SPEV concentrations. The concentration of SPEVs from infertile men diagnosed with NOA is slightly lower than vasectomized men (3.9 x109 [IQR 1.875 x109-7.675 x109] versus 5.4 x109 [IQR 2.9 x109-8 x109], p = 0.0001). The Pearson r coefficient of SPEV concentration with sperm concentration, progressive motility, and total motile sperm count was 0.238, 0.303, and 0.451, respectively. (P &amp;lt; 0.0001) Limitations, reasons for caution Because our data were collected from Taiwanese men, it is not yet known whether SPEV profiles differ among races. Wider implications of the findings Human SPEV concentration and its bio-content may be a potential non-invasive biomarker to predict the male reproductive outcome. Trial registration number not applicable

Exosomal microRNAs in lung cancer: a narrative review.

Exosomes are nanoscale extracellular vesicles secreted by cells, which can release bioactive macromolecules, such as microRNA (miRNA) to receptor cells. Exosomes can efficiently penetrate various biological barriers which mediate intercellular communication. MiRNA are a class of non-coding RNA that primarily regulate messenger RNA (mRNA) at the post-transcriptional level. MiRNA is abundant in exosomes, which plays an important role by being transported and released through exosomes secreted by lung cancer cells. This review aims to elucidate the roles of exosome-derived miRNAs in lung cancer. We focused on the roles of exosome-derived miRNAs in cancer occurrence and development, including angiogenesis, cell proliferation, invasion, metastasis, immune escape, drug resistance, and their clinical value as new diagnostic and prognostic markers for lung cancer. Exosomal miRNA can not only affect angiogenesis of lung cancer, induce epithelial-mesenchymal transformation, and promote reprogramming of tumor microenvironment, but also affect immune regulation and drug resistance transmission and participate in regulating lung cancer cell proliferation. Therefore, understanding the regulatory roles of exosomal miRNAs in tumor invasion and metastasis can provide new ideas for the treatment of lung cancer. Exosomal miRNA can provide some unique ideas on how to improve the efficiency of diagnosis and treatment of lung cancer in the future. Targeting tumor-specific exosomal miRNA represents a new strategy for clinical treatment of lung cancer, which can provide potential non-invasive biomarkers in the early diagnosis of lung cancer. Investigation of the involvement of exosomal miRNAs in the occurrence and progression of tumors can yield new opportunities for the clinical diagnosis and treatment of lung cancer.

Predicting Alzheimer's disease CSF core biomarkers: a multimodal Machine Learning approach.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current core cerebrospinal fluid (CSF) AD biomarkers, widely employed for diagnosis, require a lumbar puncture to be performed, making them impractical as screening tools. Considering the role of sleep disturbances in AD, recent research suggests quantitative sleep electroencephalography features as potential non-invasive biomarkers of AD pathology. However, quantitative analysis of comprehensive polysomnography (PSG) signals remains relatively understudied. PSG is a non-invasive test enabling qualitative and quantitative analysis of a wide range of parameters, offering additional insights alongside other biomarkers. Machine Learning (ML) gained interest for its ability to discern intricate patterns within complex datasets, offering promise in AD neuropathology detection. Therefore, this study aims to evaluate the effectiveness of a multimodal ML approach in predicting core AD CSF biomarkers. Mild-moderate AD patients were prospectively recruited for PSG, followed by testing of CSF and blood samples for biomarkers. PSG signals underwent preprocessing to extract non-linear, time domain and frequency domain statistics quantitative features. Multiple ML algorithms were trained using four subsets of input features: clinical variables (CLINVAR), conventional PSG parameters (SLEEPVAR), quantitative PSG signal features (PSGVAR) and a combination of all subsets (ALL). Cross-validation techniques were employed to evaluate model performance and ensure generalizability. Regression models were developed to determine the most effective variable combinations for explaining variance in the biomarkers. On 49 subjects, Gradient Boosting Regressors achieved the best results in estimating biomarkers levels, using different loss functions for each biomarker: least absolute deviation (LAD) for the Aβ42, least squares (LS) for p-tau and Huber for t-tau. The ALL subset demonstrated the lowest training errors for all three biomarkers, albeit with varying test performance. Specifically, the SLEEPVAR subset yielded the best test performance in predicting Aβ42, while the ALL subset most accurately predicted p-tau and t-tau due to the lowest test errors. Multimodal ML can help predict the outcome of CSF biomarkers in early AD by utilizing non-invasive and economically feasible variables. The integration of computational models into medical practice offers a promising tool for the screening of patients at risk of AD, potentially guiding clinical decisions.

Circ_0004592: An auxiliary diagnostic biomarker for gastric cancer.

Gastric cancer (GC) has a high mortality rate, and robust diagnostic biomarkers are currently lacking. However, the clinical relevance of circular RNAs (circRNAs) as GC biomarkers remains largely unexplored. To evaluate the potential of novel circRNA circ_0004592 in the early screening and prognosis of GC. High-throughput sequencing of circRNAs was performed to screen for potential target molecules. Circ_0004592 expression was examined in GC tissues, cells, and plasma. Plasma samples were collected from healthy subjects' patients, as well as from patients with benign lesions, precancerous lesions, and GC, whereafter the diagnostic accuracy of circ_0004592 was evaluated. The correlation between circ_0004592 levels in plasma and clinicopathological data of patients with GC was further analyzed. Circ_0004592 was upregulated in both the tissue and plasma of patients with GC. Further, circ_0004592 expression was higher in patients with precancerous lesions than in healthy controls while being highest in patients with GC. In the same patient, the postoperative plasma level of circ_0004592 was lower than that in the preoperative period. Moreover, circ_0004592 level was significantly correlated with tumor differentiation, tumor depth, and lymph node metastasis. The area under the curve (AUC) of plasma circ_0004592 exhibited high sensitivity and specificity for differentiating patients with GC from healthy donors. Diagnosis based on circ_0004592, carcinoembryonic antigen, and cancer antigen 199 achieved a superior AUC and was highly sensitive. Plasma circ_0004592 may represent a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

FNIRS as a biomarker for individuals with subjective memory complaints and MCI.

Identifying individuals at risk of developing dementia is crucial for early intervention. Mild cognitive impairment (MCI) and subjective memory complaints (SMCs) are considered its preceding stages. This study aimed to assess the utility of functional near-infrared spectroscopy (fNIRS) in identifying individuals with MCI and SMC. One hundred fifty-one participants were categorized into normal cognition (NC); amnestic MCI (aMCI); non-amnestic MCI (naMCI); and mild, moderate, and severe SMC groups. Task-related prefrontal hemodynamics were measured using fNIRS during a visual memory span task. Results showed significantly lower oxyhemoglobin (HbO) levels in aMCI, but not in naMCI, compared to the NC. In addition, severe SMC had lower HbO levels than the NC, mild, and moderate SMC. Receiver operating characteristic analysis demonstrated 69.23% and 69.70% accuracy in differentiating aMCI and severe SMC from NC, respectively. FNIRS may serve as a potential non-invasive biomarker for early detection of dementia. Only amnestic mild cognitive impairment (aMCI), but not non-amnestic MCI, showed lower oxyhemoglobin (HbO) than normal individuals. Reduced HbO was observed in those with severe subjective memory complaints (SMCs) compared to normal cognition (NC), mild, and moderate SMCs. Functional near-infrared spectroscopy measures were associated with performance in memory assessments. Prefrontal hemodynamics could distinguish aMCI and severe SMC from NC.

The TEOGIC study project: a comprehensive characterization of early onset gastrointestinal cancer in the Northern area of Spain

BackgroundGastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain.MethodsPatients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60–75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC.DiscussionThe underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.

Plasma circulating tumor DNA in patients with cutaneous squamous cell carcinoma: Initial experience.

e15034 Background: Circulating tumor DNA (ctDNA) has emerged as a potential noninvasive biomarker to assess tumor burden throughout cancer treatment and to aid in clinical decision-making. However, data on the use of ctDNA in cutaneous squamous cell carcinoma (cSCC) is currently lacking. In this study, we report our first experience with ctDNA in patients with cSCC. Methods: In this IRB-approved study at a tertiary care center, an initial cohort of patients with intermediate to high-risk cSCC had tissue and plasma sent for ctDNA analysis using Natera®’s proprietary bioinformatics pipeline. This cohort included 21 patients treated from 2023 to the present. Initial tissue samples were obtained through biopsy (i.e., excisional, punch, or shave), Mohs surgery, or surgical resection. Some patients had additional plasma sample(s) drawn later during or after the treatment course. Patients either received a “positive,” “positive below analytical range,” or “negative” result or had ‘insufficient sample’ to receive a result based on Natera®’s analysis. All patients were treated curatively with surgical resection with or without adjuvant radiation as per the standard of care. The assessment of gross disease was determined based on whether the patient had disease present on imaging or physical exam at the time of the plasma draw. A comparison of ctDNA results and the presence of gross disease was done using Fisher’s exact test. Results: Of the samples submitted for Natera® ctDNA analysis, 18/21 had sufficient tissue for analysis of tumor DNA. All 3 tumors with insufficient tissue were from biopsies (6/9 sufficient), while 12/12 of those from Mohs or surgical resection had sufficient tissue. The average tumor volume in these patients with insufficient samples for tumor analysis was relatively low (0.35 cm3) compared to those that resulted (17-30 cm3). 7/9 (78%) patients with gross disease had a positive ctDNA result, which was significantly greater than those with no gross disease (1/9 patients, 11%) (p = 0.004). Three patients in our cohort with an initially positive ctDNA result had multiple plasma draws, with all having a later draw demonstrating a negative ctDNA result after having surgery and/or radiation. Conclusions: Circulating tumor DNA is a reliable marker for patients with cSCC with a high tumor burden and is feasible in those with adequate tissue. However, in patients where it is only possible to obtain a small volume of tumor tissue and/or low tumor burden, ctDNA may be a less reliable biomarker. [Table: see text]

Sodium signal intensity of CSF using 1H-guided 23Na-MRI as a potential noninvasive biomarker in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline and mnestic deficits. The pathophysiology of AD is not fully understood, which renders the development of accurate tools for early diagnosis and effective therapies exceedingly difficult. In this study, we investigated the use of 23Na-MRI to measure the relative sodium signal intensities (rSSIs) in CSF in patients with AD and healthy controls. We prospectively recruited 11 patients with biomarker-diagnosed early-stage AD, as well as 12 cognitively healthy age-matched controls. All participants underwent 23Na-MRI to measure rSSI. Statistical analyses were performed to compare CSF sodium signal intensities between groups and to evaluate the specificity and sensitivity of the rSSI in the diagnosis of AD. RSSIs in CSF were significantly higher in AD patients (mean=68.6%±7.7%) compared to healthy controls (mean=56.9%±5.5%) (p<.001). There was also a significant negative correlation between rSSI in CSF and hippocampus and amygdala volumes (r=-.54 and -.49, p<.05) as well as a positive correlation with total CSF volumes (r=.81, p<.05). Receiver operating characteristic analysis showed high diagnostic accuracy for rSSI in discriminating between AD patients and healthy controls (area under the curve=.94). Our study provides evidence that rSSI in CSF is increased in AD patients in comparison to healthy controls. rSSI may serve as a potential marker for early detection and monitoring of disease progression. Larger, longitudinal studies are needed to confirm our findings and to investigate the association between rSSI in CSF and the severity of cognitive impairment.

A Four-Gene Panel in Rectal Swab Samples as a Biomarker for Colorectal Cancer Screening.

The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such dysregulation is reflected in rectal swab specimens of CRC patients and to evaluate its potential as a non-invasive approach for screening. We compared the expression level of 14 CRC-associated genes in tumor and adjacent non-tumor tissue of CRC patients and examined the correlation of their levels in tissue with paired rectal swab specimens. The level of these 14 genes in rectal swab specimens was compared among patients with CRC or polyp and control subjects, and the diagnostic potential of each dysregulated gene and the gene panel were evaluated. The expression of CXCR2, SAA, COX1, PPARδ, PPARγ, Groγ, IL8, p21, c-myc, CD44 and CSF1 was significantly higher in CRC, and there was a significant correlation in the levels of most of them between the CRC and rectal swab specimens. In the training study, we showed that CD44, IL8, CXCR2 and c-myc levels were significantly higher in the rectal swab specimens of the CRC patients. Such result was confirmed in the validation study. A panel of these four genes was developed, and ROC analysis showed that this four-gene panel could identify CRC patients with an AUC value of 0.83 and identify overall polyp and precancerous adenoma patients with AUC values of 0.6522 and 0.7322, respectively. Finally, the predictive study showed that the four-gene panel demonstrated sensitivities of 63.6%, 76.9% and 88.9% in identifying overall polyp, precancerous adenoma and CRC patients, respectively, whereas the specificity for normal subjects was 72.2%. The expression of CRC-associated genes in rectal swab specimens reflects the dysregulation status in colorectal tissue, and the four-gene panel is a potential non-invasive biomarker for early precancerous adenoma and CRC screening.

Rest and stress aortic flow analysis by CMR in MyoFit46

Abstract Background Aortic stiffness is a strong predictor of future cardiovascular events and all-cause mortality. Aortic stiffness has never been measured during adenosine stress perfusion before, and may provide valuable relationship about this relationship. Aim To investigate if there are differences between aortic stiffness and conditions of rest and stress perfusion, in an older age-homogenous population-based cohort. Methods 203 participants from the longitudinal 1946 Medical Research Council National Survey of Health and Development British birth cohort were included. Cardiovascular Magnetic Resonance (CMR) imaging was performed at rest and during adenosine stress perfusion. 3 established and validated biomarkers of aortic stiffness were reported - pulse wave velocity, distensibility and beta stiffness, at rest and stress perfusion. All variables were non-normally distributed, therefore the Wilcoxon signed-rank test was used to look for significant differences between rest and stress. Results Aortic stiffness increased significantly during adenosine stress perfusion, shown by all biomarkers of aortic stiffness used: pulse wave velocity (p = &amp;lt;0.001), distensibility (p = &amp;lt;0.001), and beta stiffness (p = &amp;lt;0.001). However, the aortas of participants with a higher resting aortic stiffness at baseline were less dynamic (little if any aortic stiffness change with stress) when compared to those with low resting aortic stiffness. Conclusion It is feasible to measure aortic stiffness during adenosine stress perfusion. In healthy aortas, aortic stiffness increases in the acute phase of adenosine stress suggesting a new potential mechanism for the body response to adenosine – peripheral chemoreceptor reflex activation. Stiffer arteries at baseline are less modifiable and stress aortic flow CMR has the potential to identify these persons permitting early targeted therapy. Change in aortic stiffness, measured by stress aortic flow CMR is therefore a potential non-invasive biomarker of aortic health.

#2229 miR-186, a potential noninvasive diagnostic biomarker of Membranous nephropathy in urinary microparticles

Abstract Background and Aims Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome, and is associated with podocyte damage and proteinuria. Invasive biopsy is the gold-standard diagnostic method for this disease. The use of specific biomarkers, such as microparticles (MPs) originating from damaged podocytes released in a patient's urine, has been proposed as an early, noninvasive, and repetitive diagnostic method. According to the previous studies, MPs derived from podocytes are present in the urine of patients with different glomerulonephritis, such as diabetic nephropathy, lupus nephritis, renal injury in preeclampsia, and renovascular hypertensive disorders. The analysis of urinary microparticle-derived miRNAs from patients with kidney diseases can help detect diagnostic biomarkers. This study aimed to analyze podocyte damage-related miRNAs in MN, miR-30c, miR-135, and miR-18 in the urinary MP of MN patients to identify appropriate candidate biomarkers for MN Method Urine samples from 30 patients with membranous nephropathy and 16 healthy individuals were collected to extract podocyte MPs using ultracentrifugation. Characterization of these particles was determined using the specific protein marker of MPs, TSG-101, and the podocyte-specific marker Nephrin, by western blotting, and SEM was used to check the size and morphology. The expression levels of microRNAs extracted from podocyte MPs, miR-30c, miR-135, and miR-186, were also evaluated by real-time PCR. Results The evaluation of the characteristics of MPs showed that there were many particles with a size of more than 100 nm in the urine sample, and there were higher levels of the specific markers TSG-101 and Nephrin in the urine samples of MGN patients than in the control samples (P &amp;lt; 0.001). The expression level of miR-186 was compared between the three studied groups and based on the results of the expression of this miRNA in the group of membranous nephropathy patients compared to healthy people group, there was a significant increase in expression (P = 0.000) Conclusion This study showed that although the expression levels of miR-186 in podocyte MPs samples extracted from the urine of patients with MN were significantly changed compared to the studied controls, more studies should be performed to determine the diagnostic values.

Gut metagenomic analysis of gastric cancer patients reveals Akkermansia, Gammaproteobacteria, and Veillonella microbiota as potential non-invasive biomarkers

The goal of the study was to investigate the changes in the gut microbiota during the advancement of gastric cancer (GC) and identify pertinent taxa associated with the disease. We used a public fecal amplicon gastric cancer dataset from the Sequence Retrieval Archive (SRA), of patients with GC, gastritis, and healthy individuals. We did sequence pre-processing, including quality filtering of the sequences. Then, we performed a diversity analysis, evaluating α- and β-diversity. Next, taxonomic composition analysis was performed and the relative abundances of different taxa at the phylum and genus levels were compared between GC, gastritis, and healthy controls. The obtained results were subsequently subjected to statistical validation. To conclude, metagenomic function prediction was carried out, followed by correlation analysis between the microbiota and KEGG pathways. α analysis revealed a significant difference between male and female categories, while β analysis demonstrated significant distinctions between GC, gastritis, and healthy controls, as well as between sexes within the GC and gastritis groups. The statistically confirmed taxonomic composition analysis highlighted the presence of the microbes Bacteroides and Veillonella. Furthermore, through metagenomic prediction analysis and correlation analysis with pathways, three taxa, namely Akkermansia, Gammaproteobacteria, and Veillonella, were identified as potential biomarkers for GC. Additionally, this study reports, for the first time, the presence of two bacteria, Desulfobacteriota and Synergistota, in GC, necessitating further investigation. Overall, this research sheds light on the potential involvement of gut microbiota in GC pathophysiology; however, additional studies are warranted to explore its functional significance.

A comprehensive evaluation of serum circCSPP1 as a novel diagnostic and prognostic biomarker for gastric cancer

PurposeGastric cancer (GC) has high incidence and mortality due to its low early screening efficiency. Circular RNAs (CircRNAs) are a new class of non-coding RNAs which is closely related to GC. Nevertheless, the clinical application value of circRNAs in GC are largely unknown. Therefore, we studied the role of a novel circRNA named circCSPP1 in patients with GC. MethodsCircRNA sequencing was performed to screen out the target molecule. Real-time fluorescent quantitative PCR (RT-qPCR) was utilized to detect the expression level of circCSPP1 in GC tissues, cells, and serum. Gel and Sanger sequencing were utilized to verify the ring structure of circCSPP1. RNase R enzyme digestion experiment and actinomycin D experiment were verifed the advantage of circCSPP1 as a diagnostic biomarker in patients with GC when that compared with linear RNA. The correlation between the expression level of serum circCSPP1 and clinicopathological data of GC patients was further analyzed. Receiver operating characteristic curve (ROC) and the area under ROC curve (AUC) were utilied to evaluate the diagnostic performance. ResultsCircCSPP1 has a circular structure which with resistance to RNA exonuclease digestion and long half-life compared with linear RNA. In our study, circCSPP1 was first found up-regulated in patients with GC. Serum circCSPP1 level was decreased significantly after surgical resection whereas increased after recurrence. High expression of circCSPP1 was associated with poor survival rates. The expression level of circCSPP1 was significantly correlated to tumor size, T stage, lymph node metastasis, and TNM stage. The AUC of serum circCSPP1 was 0.834, with high sensitivity and specificity in discriminating patients with GC from healthy donors. More importantly, the combined diagnosis of circCSPP1, CEA, and CA19–9 achieved the superior AUC of 0.882, with the highest specificity. ConclusionSerum circCSPP1 may prove to be a potential non-invasive auxiliary diagnostic biomarker for patients with GC.

Circ_0006949 as a potential non-invasive diagnosis biomarker promotes the proliferation of NSCLC cells via miR-4673/GLUL axis

The 5-year survival for non-small cell lung cancer (NSCLC) remains <20 %, primarily due to the early symptoms of lung cancer are inconspicuous. Prompt identification and medical intervention could serve as effective strategies for mitigating the death rate. We therefore set out to identify biomarkers to help diagnose NSCLC. CircRNA microarray and qRT-PCR reveal that sputum circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC, which can enhance the proliferation and clone formation, regulate the cell cycle, and accelerate the migration and invasion of NSCLC cells. Circ_0006949 and miR-4673 are predominantly co-localized in the cytoplasm of NSCLC cell lines and tissues; it upregulates GLUL by adsorption of miR-4673 through competing endogenous RNAs mechanism. The circ_0006949/miR-4673/GLUL axis exerts pro-cancer effects in vitro and in vivo. Circ_0006949 can boost GLUL catalytic activity, and they are highly expressed in NSCLC tissues and correlate with poor prognosis. In summary, circ_0006949 is a potential biomarker for the early diagnosis and therapy of NSCLC. This novel sputum circRNA is statistically more predictive than conventional serum markers for NSCLC diagnosis. Non-invasive detection of patients with early-stage NSCLC using sputum has shown good potential for routine diagnosis and possible screening.