Non-invasive Biomarkers Research Articles

Detection of Catalase and 4-Hydroxynonenal as Detective Biomarkers in Iraqi Breast Cancer

Breast cancer is the most common malignant tumor among women and a leading cause of cancer-related death. Early diagnosis is critical for improving treatment outcomes. The objective of this study is to determine and examine catalase (CAT) and 4-hydroxynonenal (4-HNE) markers as non-invasive biomarkers for early detection in Iraqi breast cancer. A case-control study of 150 participants was further divided into 75 women with a diagnosis of breast cancer and 75 healthy controls. In the present study, blood samples were collected for the determination of serum CAT and 4-HNE levels using an enzyme-linked immunosorbent assay technique. The biochemical markers urea and creatinine were determined by automated Cobas c311. Hemoglobin concentration (HB)-and total white blood cell (WBC) count was done by an automated hematology analyzer. Statistical analyses were performed using the SPSS version 24, where receiver operating characteristics (ROC) analysis was used to assess diagnostic performance. CAT activity was significantly reduced in the patient group (6.07±1.19 pg/ml) compared to controls (12.11±2.74 pg/ml), while 4-HNE was significantly elevated in the patient group (11.43±2.41 pg/ml) compared to control (3.83±1.02 pg/ml). Among hematology analyzer, there was a significant difference in HB and WBC between patients and controls. Roc analyses demonstrated a sensitivity of 100% for CAT and 98% for 4-HNE. Reduced serum levels of CAT and elevated 4-HNE levels in Iraqi breast cancer may serve as new diagnostic biomarkers for breast cancer, highlighting their role in disease progression.

Clinical significance of HIF-1α, ET-1, and NO as biomarkers in chronic obstructive pulmonary disease patients with pulmonary hypertension.

Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), with repeated infections and airflow limitation leading to endothelial dysfunction. The objective of this study was to retrospectively investigate the clinical significance of serum hypoxia-inducible factor 1-alpha (HIF-1α), plasma endothelin-1 (ET-1), and nitric oxide (NO) as non-invasive blood biomarkers for diagnosing patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A total of 230 AECOPD patients were assessed for serum HIF-1α, plasma ET-1, and NO levels using Doppler echocardiography and blood tests. Clinical characteristics, including age, COPD duration, and comorbidities, were compared between patients with and without PH. The diagnostic value was determined through ROC analysis. Pearson correlation and multivariate logistic analyses explored the correlation of biomarkers in AECOPD with PH. Serum HIF-1α, plasma ET-1, and NO levels showed significant differences between COPD patients with and without PH. The combination model (0.027 * HIF-1α + 0.028 * ET-1 - 0.049 * NO) demonstrated an AUC of 0.89, indicating superior diagnostic value compared to individual biomarkers. Multivariate logistic analysis identified smoking, higher GOLD grade, hypertension, and elevated levels of HIF-1α, ET-1, and NO as independent risk factors for AECOPD. Positive correlations were observed between serum HIF-1α and plasma ET-1 levels with pulmonary artery systolic pressure (PASP), while NO demonstrated a negative correlation. Serum HIF-1α, plasma ET-1, and NO were associated with AECOPD and PH, and detecting individual or combined levels of these biomarkers in the blood can predict COPD-related PH.

Impact of Dupilumab on Skin Surface Lipid-RNA Profile in Severe Asthmatic Patients.

The analysis of skin surface lipid-RNAs (SSL-RNAs) provides a non-invasive method for understanding the molecular pathology of atopic dermatitis (AD), but its relevance to asthma remains uncertain. Although dupilumab, a biologic drug approved for both asthma and AD, has shown efficacy in improving symptoms for both conditions, its impact on SSL-RNAs is unclear. This study aimed to investigate the impact of dupilumab treatment on SSL-RNA profiles in patients with severe asthma. An SSL-RNA analysis was performed before and after administering dupilumab to asthma patients requiring this intervention. Skin samples were collected non-invasively from patients before and after one year of dupilumab treatment. Although 26 patients were enrolled, an SSL-RNA analysis was feasible in only 7 due to collection challenges. After dupilumab treatment, improvements were observed in asthma symptoms, exacerbation rates, and lung function parameters. Serum levels of total IgE and periostin decreased. The SSL-RNA analysis revealed the differential expression of 218 genes, indicating significant down-regulation of immune responses, particularly those associated with type 2 inflammation, suggesting potential improvement in epithelial barrier function. Dupilumab treatment may not only impact type 2 inflammation but also facilitate the normalization of the skin. Further studies are necessary to fully explore the potential of SSL-RNA analysis as a non-invasive biomarker for evaluating treatment response in asthma.

Biomarkers suitable for early detection of intrathoracic cancers in primary care: a systematic review.

Intrathoracic cancers, including lung cancer, mesothelioma, and thymoma, present diagnostic challenges in primary care. Biomarkers could resolve some challenges. We synthesized evidence on biomarkers performance for intrathoracic cancer detection in low-prevalence settings. A search in EMBASE and MEDLINE included studies that recruited participants with suspected intrathoracic cancer and reported on at least one diagnostic measure for a validated, non-invasive biomarker. Studies were excluded if participants were recruited based on a pre-established diagnosis. Fifty-two studies were included, reporting on 108 individual biomarkers and panels. CEA, CYFRA 21.1, and VEGF were evaluated for lung cancer and mesothelioma. For lung cancer, CEA and CYFRA 21.1 were most studied, with AUCs of 0.48-0.90 and 0.48-0.83, respectively. Pro-GRP and NSE had the highest NPVs (98.2%, 96.9%), while Early-CDT and MSC panels showed NPVs of 99.3% and 99.0% in smokers. For mesothelioma, Fibrillin-3 and mesothelin plus osteopontin had AUCs of 0.93 and 0.91, respectively. Thymoma panels (Binding AcHR + StrAb) and (Binding AcHR + Modulating AcHR + StrAb) had 100% NPVs in myasthenia gravis patients. The review highlights the performance of some biomarkers. However, few were evaluated in low-prevalence settings. Further evaluation is necessary before implementing these biomarkers for intrathoracic cancers in primary care.

The correlation between Life’s essential 8 and cardiovascular disease and mortality in individuals with nonalcoholic fatty liver disease: a cross-sectional study

It is currently unclear whether there is a connection between Life’s Essential 8 (LE8) and cardiovascular disease (CVD), as well as mortality in people with nonalcoholic fatty liver disease (NAFLD). Our goal was to explore these relationships by examining data collected in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. We identified eligible participants with NAFLD based on NHANES 2005–2018 data. CVD status was acquired through self-reported information, and using the National Death Index, mortality data were prospectively matched. The diagnosis of NAFLD relied on noninvasive biomarkers. The research involved 9094 individuals who were identified as having NAFLD, with a mean age of 52.05 years. Each incremental LE8 score exhibited a significant association, leading to a 3%, 3%, 4%, 3%, 3%, 4%, and 4% reduction in the odds of experiencing CVD, ischemic heart disease, congestive heart failure, coronary heart disease, heart attack, angina, and stroke in individuals with NAFLD. A strong correlation was found between maintaining a superior level of Cardiovascular Health (CVH), as shown by a LE8 score ranging from 80 to 100, and a reduced occurrence of CVD and its various forms in NAFLD (all p for trend < 0.0001). Likewise, LE8 demonstrated protective benefits on mortality in NAFLD, showing that following a high CVH (in contrast to low CVH) was linked to reductions of 64%, 71%, and 74% in all-cause, CVD, and cancer mortality, respectively. Restricted cubic spline analyses suggested noteworthy dose-response relationships between LE8 and CVD, specifically its types in NAFLD, and a nonlinear correlation with CVD mortality. Interaction analyses highlighted age and race as significant effect modifiers. CVH, as evaluated by LE8, demonstrated an independent association with decreased odds of CVD and mortality risk in individuals with NAFLD. Our findings substantiate that adhering to LE8 may alleviate the excessive burden of CVD and mortality in the context of NAFLD.

Elevated Aβ aggregates in feces from Alzheimer’s disease patients: a proof-of-concept study

BackgroundMisfolding and aggregation of amyloid β (Aβ), along with neurofibrillary tangles consisting of aggregated Tau species, are pathological hallmarks of Alzheimer’s disease (AD) onset and progression. In this study, we hypothesized the clearance of Aβ aggregates from the brain and body into the gut.MethodsTo investigate this, we used surface-based fluorescence intensity distribution analysis (sFIDA) to determine the Aβ aggregate concentrations in feces from 26 AD patients and 31 healthy controls (HC).ResultsAβ aggregates were detectable in human feces and their concentrations were elevated in AD patients compared to HC (specificity 90.3%, sensitivity 53.8%).ConclusionThus, fecal Aβ aggregates constitute a non-invasive biomarker candidate for diagnosing AD. Whether digestion-resistant Aβ aggregates in feces are secreted via the liver and bile or directly from the enteric neuronal system remains to be elucidated.

Integrin β5, a noninvasive diagnostic biomarker, is associated with unfavorable prognosis and immunotherapy efficacy in gastric cancer

BackgroundIntegrin β5 (ITGB5) is a pivotal player in the pathogenesis of gastric cancer (GC). We aimed to explore the potential value of ITGB5 as a predictor of diagnosis and immunotherapy in gastric cancer.MethodsThe expression of ITGB5 in GC was assessed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and verified through quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Kaplan-Meier curves were conducted to evaluate the prognostic significance. The immune cells infiltration, tumor mutational burden (TMB), and immunophenoscore (IPS) were examined using CIBERSORT, TIMER, and TISIDB. In addition, colony formation, scratch assays, and transwell assays were employed to determine the impact on tumor progression and metastasis. CD276 expression was detected by western blotting following the knockdown of ITGB5. ELISA was utilized to measure serum ITGB5 levels.ResultsThe expression of ITGB5 in GC tissue surpassed that in normal tissue, it might contribute to GC pathogenesis through pathways including PI3K-AKT, ECM-receptor interaction, and TGF-beta. The elevated ITGB5 expression is associated with poor prognosis in GC patients. In addition, a strong positive association between ITGB5 overexpression and the infiltration levels of macrophages and monocytes, and it significantly influenced immune response. Moreover, lower expression of ITGB5 was associated with better immunotherapy efficacy. Subsequent investigation demonstrated that silencing of ITGB5 suppressed the proliferation and migration of GC cell lines in vitro. ITGB5 expression was positively correlated with CD276 expression and the knockdown of ITGB5 resulted a notable decrease CD276 expression. Futhermore, a significantly high level of serum ITGB5 was observed in GC patients. The combined assessment of ITGB5, CEA, and CA19-9 improved the diagnostic accuracy.ConclusionsITGB5 potentially serve as both a diagnostic biomarker and therapeutic target in managing GC.

Innovative approaches to metabolic dysfunction-associated steatohepatitis diagnosis and stratification

The global rise in Metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic dysfunction-associated steatohepatitis (MASH) highlights the urgent necessity for noninvasive biomarkers to detect these conditions early. To address this, we endeavored to construct a diagnostic model for MASLD/MASH using a combination of bioinformatics, molecular/biochemical data, and machine learning techniques. Initially, bioinformatics analysis was employed to identify RNA molecules associated with MASLD/MASH pathogenesis and enriched in ferroptosis and exophagy. This analysis unveiled specific networks related to ferroptosis (GPX4, LPCAT3, ACSL4, miR-4266, and LINC00442) and exophagy (TSG101, HGS, SNF8, miR-4498, miR-5189–5p, and CTBP1-AS2). Subsequently, serum samples from 400 participants (151 healthy, 150 MASH, and 99 MASLD) underwent biochemical and molecular analysis, revealing significant dyslipidemia, impaired liver function, and disrupted glycemic indicators in MASLD/MASH patients compared to healthy controls. Molecular analysis indicated increased expression of LPCAT3, ACSL4, TSG101, HGS, and SNF8, alongside decreased GPX4 levels in MASH and MASLD patients compared to controls. The expression of epigenetic regulators from both networks (miR-4498, miR-5189–5p, miR-4266, LINC00442, and CTBP1-AS2) significantly differed among the studied groups. Finally, supervised machine learning models, including Neural Networks and Random Forest, were applied to molecular signatures and clinical/biochemical data. The Random Forest model exhibited superior performance, and molecular features effectively distinguished between the three studied groups. Clinical features, particularly BMI, consistently served as discriminatory factors, while biochemical features exhibited varying discriminant behavior across MASH, MASLD, and control groups. Our study underscores the significant potential of integrating diverse data types to enable early detection of MASLD/MASH, offering a promising approach for non-invasive diagnostic strategies.

Computed tomography perfusion as a predictor of gastric cancer grades

BackgroundGastric cancer stands as one of the most prevalent malignancies globally, conventional endoscopic specimens have been the primary means of diagnosing preoperative gastric histopathology, however, their limitations in capturing intra-tumor heterogeneity compromise their efficacy in evaluating angiogenesis. Perfusion Computed Tomography (P-CT) emerges as a pivotal functional imaging modality, facilitating objective assessment of tissue perfusion, serving as a marker of angiogenesis. So, our research objective was to evaluate the efficacy of CT perfusion imaging in the prediction of histological grades of gastric tumors using quantitative perfusion parameters such as permeability surface (PS), blood flow (BF), mean transient time (MTT), and blood volume (BV), in addition to the qualitative scoring system then comparing the findings with the histopathological results.ResultsPS and BF were statistically significant predictors of the grade of differentiation, their odds ratio (OR) was (1.05, 95% CI 1.02–1.09, for each of them) (P = 0.004, P = 0.009, respectively). MTT also emerged as a significant predictor of the grade of differentiation with an OR of 0.76 (95% CI 0.57–0.93, P = 0.025). Using multivariate logistic regression model, PS was the most potent individual P-CT predictor of differentiation of the grade and the diagnosis of poorly differentiated tumors at ≥ 39 mL/100 g/min cut off point, followed by BF at ≥ 82.2 mL/100 g/min, and MTT at < 8.4 s. Regarding the qualitative scoring system P-CT, poorly differentiated tumors generally received higher scores of PS (P < 0.001), BF (P < 0.001), and BV (P = 0.017), than well and moderately differentiated tumors, however, MTT showed that poorly differentiated tumors were more frequently scored as low compared to well and moderately differentiated tumors (P < 0.001).ConclusionsP-CT is an innovative, non-invasive biomarker for predicting gastric cancer grade by quantitative and qualitative assessment by P-CT parameters (PS, BF and MTT) with particular role of PS as the strongest individual P-CT predictor of differentiation grade followed by BF and MTT at specific cut off points.

Prognostic significance of the modified Glasgow Prognostic Score in NSCLC patients undergoing immune checkpoint inhibitor therapy: a meta-analysis.

The modified Glasgow Prognosis Score (mGPS), which considers both inflammatory response and nutritional status, has been linked to the prognosis of various tumors. The relationship between mGPS and non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs) is still a subject of debate. This meta-analysis aims to comprehensively assess the association between mGPS and survival in NSCLC treated with ICIs. A thorough review of studies from PubMed, Web of Science, Scopus, and Embase was conducted up to June 4, 2024. Fixed-effect or random-effect models were employed, combining hazard ratios (HRs) and 95% confidence intervals (CI), to assess the prognostic value of mGPS for OS and PFS in patients with NSCLC receiving immunotherapy. A total of 1,022 patients from 11 studies were recruited. Combined results showed that mGPS elevation was significantly associated with poor OS (HR = 1.63, 95%CI: 1.42-1.87, P < 0.01) and PFS (HR = 1.71, 95%CI: 1.31-2.24, P < 0.01). Subgroup analysis and sensitivity analysis further determined the predictive effect of elevated mGPS on OS and PFS deterioration in NSCLC patients receiving immunotherapy. mGPS can be used as a good noninvasive biomarker to demonstrate prognostic and clinical significance in patients with NSCLC undergoing immunotherapy. http://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023432661.

Prediction of prostate cancer recurrence after radiotherapy using a fused machine learning approach: utilizing radiomics from pretreatment T2W MRI images with clinical and pathological information

The risk of biochemical recurrence (BCR) after radiotherapy for localized prostate cancer (PCa) varies widely within standard risk groups. There is a need for low-cost tools to more robustly predict recurrence and personalize therapy. Radiomic features from pretreatment MRI show potential as noninvasive biomarkers for BCR prediction. However, previous research has not fully combined radiomics with clinical and pathological data to predict BCR in PCa patients following radiotherapy.&#xD;Purpose: This study aims to predict 5-year BCR using radiomics from pretreatment T2W MRI and clinical-pathological data in PCa patients treated with radiation therapy, and to develop a unified model compatible with both 1.5T and 3T MRI scanners.&#xD;Methods: A total of 150 T2W scans and clinical parameters were preprocessed. Of these, 120 cases were used for training and validation, and 30 for testing. Four distinct machine learning models were developed: Model 1 used radiomics, Model 2 used clinical and pathological data, and Model 3 combined these using late fusion. Model 4 integrated radiomic and clinical-pathological data using early fusion.&#xD;Results: Model 1 achieved an AUC of 0.73, while Model 2 had an AUC of 0.64 for predicting outcomes in 30 new test cases. Model 3, using late fusion, had an AUC of 0.69. Early fusion models showed strong potential, with Model 4 reaching an AUC of 0.84, highlighting the effectiveness of the early fusion model.&#xD;Conclusions: This study is the first to use a fusion technique for predicting BCR in PCa patients following radiotherapy, utilizing pre-treatment T2W MRI images and clinical-pathological data. The methodology improves predictive accuracy by fusing radiomics with clinical-pathological information, even with a relatively small dataset, and introduces the first unified model for both 1.5T and 3T MRI images.

Advanced imaging techniques and non-invasive biomarkers in pediatric brain tumors: state of the art.

In the pediatric age group, brain neoplasms are the second most common tumor category after leukemia, with an annual incidence of 6.13 per 100,000. Conventional MRI sequences, complemented by CT whenever necessary, are fundamental for the initial diagnosis and surgical planning as well as for post-operative evaluations, assessment of response to treatment, and surveillance; however, they have limitations, especially concerning histopathologic or biomolecular phenotyping and grading. In recent years, several advanced MRI sequences, including diffusion-weighted imaging, diffusion tensor imaging, arterial spin labelling (ASL) perfusion, and MR spectroscopy, have emerged as a powerful aid to diagnosis as well as prognostication; furthermore, other techniques such as diffusion kurtosis, amide proton transfer imaging, and MR elastography are being translated from the research environment to clinical practice. Molecular imaging, especially PET with amino-acid tracers, complement MRI in several aspects, including biopsy targeting and outcome prediction. Finally, radiomics with radiogenomics are opening entirely new perspectives for a quantitative approach aiming at identifying biomarkers that can be used for personalized, precision management strategies.

Exploring serum bile acids as potential noninvasive biomarkers for nonalcoholic fatty liver disease

BackgroundBile acids are vital regulators of liver metabolism, and their dysregulation is closely linked with the progression of nonalcoholic fatty liver disease (NAFLD). Profiling these bile acids may provide valuable diagnostic and prognostic markers for these conditions. This study aimed to evaluate bile acid profiles in NAFLD patients and assess their potential as biomarkers for diagnosing and predicting disease progression. Serum levels of 14 bile acids were measured in 25 normal healthy controls (NHC), 35patients with metabolic dysfunction–associated steatotic liver disease (MASLD), and 40 patients with NASH, categorized by the NAFLD Activity Score (NAS). Quantification was performed using high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS).ResultsPrimary unconjugated bile acids, CA and CDCA, along with conjugated acids GCA, GCDCA, TCA, and TCDCA, were significantly elevated in both MASLD and NASH compared to NHC (all p < 0.05). While levels increased progressively from NHC to MASLD to NASH, no significant differences were observed between MASLD and NASH except for GCA and TCA (P < 0.05). Similarly, secondary bile acids LCA, TLCA, GUDCA, and TUDCA were higher in MASLD and NASH compared to NHC (all p < 0.05).Logistic regression identified CA (odds ratio = 2.05, p = 0.02), CDCA (odds ratio = 1.58, p = 0.04), GCA (odds ratio = 1.92, p = 0.03) and DCA (odds ratio = 2.06, p = 0.04) as significant predictors of fibrosis. For active inflammation, GCA (odds ratio = 2.04, p = 0.04), and TCA (odds ratio = 1.94, p = 0.04) were significant predictors. In steatosis, CA, CDCA, GCA, DCA, TDCA, TLCA, and UDCA were notable predictors, with high odds ratios.ConclusionThe study highlights significant alterations in bile acid profiles associated with NAFLD progression. Specific bile acids, such as CA, GCA, TCA, and TCDCA are strong predictors of disease severity, indicating their potential as biomarkers for NAFLD treatment and prognosis.

The role of markers of endothelial dysfunction in the pathogenesis of coronary microvascular dysfunction in patients with non-obstructive coronary artery disease

Aim. To study the potential of non-invasive biomarkers in the diagnosis of coronary microvascular dysfunction (CMD) and prediction of the course of heart failure with preserved ejection fraction (HFpEF) in non-obstructive coronary artery disease.Materials and methods. The 12-month observational study included 118 consecutive patients (6 patients dropped out of the study due to contact loss) with non-obstructive coronary artery disease (CAD) and HFpEF (62 [59; 64]%). At the beginning of the study, serum levels of several biomarkers were assessed using the enzyme immunoassay: N-terminal pro-B-type natriuretic peptide (NT-proBNP), vascular endothelial growth factor (VEGF), and endothelin-1. Coronary flow reserve (CFR) was examined using dynamic single photon emission computed tomography. In the absence of obstructive CAD, CMD was defined as a global decrease in CFR ≤ 2. Echocardiography was used to determine parameters of hemodynamics, LV diastolic dysfunction, and myocardial stress. LV global longitudinal strain (GLS) was assessed using 2D speckle tracking.Results. The patients were divided into groups depending on the presence of CMD: group 1 included patients with CMD (n = 43), group 2 included those without it (n = 75). In patients in group 1, serum levels of endothelin-1 were 1.9 times higher (p = 0.012), levels of VEGF were 2.16 times higher (p = 0.008), and the concentration of NT-proBNP was 2.6 times higher (p = 0.004) than in patients in group 2. According to the ROC analysis, the concentrations of endothelin-1 ≥ 6.9 pg / ml (AUC = 0.711; p = 0.040) and VEGF ≥ 346.7 pg / ml (AUC = 0.756; p = 0.002) were considered as markers associated with the presence of CMD in patients with non-obstructive CAD. The multivariate regression analysis showed that only the presence of CMD (odds ratio (OR) 2.42; 95% confidence interval (95% CI) 1.26–5.85; p &lt; 0.001) and an increase in NT-proBNP ≥ 760.5 pg / ml (OR 1.33; 95% CI 1.08–3.19; p = 0.023) were factors associated with adverse events, and their combination increased the risk of HFpEF progression by more than 3 times (OR 3.18; 95% CI 2.76–7.98; p &lt; 0.001), whereas markers of endothelial dysfunction were not independent predictors. Conclusion. Endothelin-1 ≥ 6.9 pg / ml and VEGF ≥ 346.7 pg / ml can be used as non-invasive markers for the diagnosis of CMD. However, markers of endothelial dysfunction were not independent predictors of HFpEF progression in patients with non-obstructive CAD during 12-month follow-up.

Insights about exosomal circular RNAs as novel biomarkers and therapeutic targets for hepatocellular carcinoma.

One of the most prevalent pathological types of Primary Liver Cancer (PLC) is the Hepatocellular Carcinoma (HCC) poses a global health issue. The high recurrence and metastasis rate of HCC, coupled with a low 5-year survival rate, result in a bleak prognosis. Exosomes, small extracellular vesicles released by various cells, contain diverse non-coding RNA molecules, including circular RNAs (circRNAs), which play a significant role in intercellular communication and can impact HCC progression. Studies have revealed the potential clinical applications of exosomal circRNAs as biomarkers and therapeutic targets for HCC. These circRNAs can be transferred via exosomes to nearby non-cancerous cells, thereby regulating HCC progression and influencing malignant phenotypes, such as cell proliferation, invasion, metastasis, and drug resistance. This review provides a comprehensive overview of the identified exosomal circRNAs, highlighting their potential as non-invasive biomarkers for HCC, and suggesting new perspectives for HCC diagnosis and treatment. The circRNA from exosomal organelles promotes metastasis and immune scape because of their unique chirality which is different from the Biomolecular Homochirality.

Salivary biomarkers: a promising approach for predicting immunotherapy response in head and neck cancers.

Head and neck cancers, including cancers of the mouth, throat, voice box, salivary glands, and nose, are a significant global health issue. Radiotherapy and surgery are commonly used treatments. However, due to treatment resistance and disease recurrence, new approaches such as immunotherapy are being explored. Immune checkpoint inhibitors (ICIs) have shown promise, but patient responses vary, necessitating predictive markers to guide appropriate treatment selection. This study investigates the potential of non-invasive biomarkers found in saliva, oral rinses, and tumor-derived exosomes to predict ICI response in head and neck cancer patients. The tumor microenvironment significantly impacts immunotherapy efficacy. Oral biomarkers can provide valuable information on composition, such as immune cell presence and checkpoint expression. Elevated tumor mutation load is also associated with heightened immunogenicity and ICI responsiveness. Furthermore, the oral microbiota may influence treatment outcomes. Current research aims to identify predictive salivary biomarkers. Initial studies indicate that tumor-derived exosomes and miRNAs present in saliva could identify immunosuppressive pathways and predict ICI response. While tissue-based markers like PD-L1 have limitations, combining multiple oral fluid biomarkers could create a robust panel to guide treatment decisions and advance personalized immunotherapy for head and neck cancer patients.

Circulating Tumor Cell Count and Overall Survival in Patients With Metastatic Hormone-Sensitive Prostate Cancer

In metastatic hormone-sensitive prostate cancer (mHSPC), new first-line combination therapies have enhanced overall survival (OS), but clinical outcomes for individual patients vary greatly and are difficult to predict. Peripheral blood circulating tumor cell (CTC) count is the most extensively validated prognostic liquid biomarker in metastatic castration-resistant prostate cancer (mCRPC), and recent studies have suggested that it may also be informative in mHSPC. To examine the prognostic value of CTC count in men with mHSPC. In this prognostic study, peripheral blood was drawn at registration (baseline) and at progression to mCRPC in the S1216 study (March 1, 2013, to July 15, 2017), a phase 3, prospective, randomized clinical trial in men with mHSPC. The CTCs were enumerated using a US Food and Drug Administration-cleared isolation platform. Counts were categorized as 0, 1 to 4, or 5 or more CTCs per 7.5 mL based on the prognostic value of these cut points in prior studies. The data analysis was performed between October 28, 2022, and June 15, 2023. Metastatic hormone-sensitive prostate cancer. Circulating tumor cell count was evaluated for an association with 3 prespecified trial end points: OS, progression-free survival, and 7-month prostate-specific antigen, after adjusting for other baseline covariates using proportional hazards and logistic regression models. Of 1313 S1216 participants (median [IQR] age, 68 [44-92] years), evaluable samples from 503 (median [IQR] age, 69 [46-90] years) with newly diagnosed mHSPC were collected at baseline, and 93 samples were collected at progression. Baseline counts were 5 or more CTCs per 7.5 mL in 60 samples (11.9%), 1 to 4 CTCs per 7.5 mL in 107 samples (21.3%), and 0 CTCs per 7.5 mL in 336 samples (66.8%). Median OS for men with 5 or more CTCs per 7.5 mL was 27.9 months (95% CI, 24.1-31.2 months) compared with 56.2 months (95% CI, 45.7-69.8 months) for men with 1 to 4 CTCs per 7.5 mL and not reached at 78.0 months follow-up for men with 0 CTCs per 7.5 mL. After adjusting for baseline clinical covariates, men with 5 or more CTCs per 7.5 mL at baseline had a significantly higher hazard of death (hazard ratio, 3.22; 95% CI, 2.22-4.68) and disease progression (hazard ratio, 2.46; 95% CI, 1.76-3.43) and a lower likelihood of prostate-specific antigen complete response (odds ratio, 0.26; 95% CI, 0.12-0.54) compared with men with 0 CTCs per 7.5 mL at baseline. Adding baseline CTC count to other known prognostic factors (covariates only: area under the curve, 0.73; 95% CI, 0.67-0.79) resulted in an increased prognostic value for 3-year survival (area under the curve, 0.79; 95% CI, 0.73-0.84). In this prognostic study, the findings validate CTC count as a prognostic biomarker that improved upon existing prognostic factors and estimated vastly divergent survival outcomes regardless of subsequent lines of therapy. As such, baseline CTC count in mHSPC may serve as a valuable noninvasive biomarker to identify men likely to have poor survival who may benefit from clinical trials of intensified or novel regimens.

Circulating tumour DNA in patients with hepatocellular carcinoma across tumour stages and treatments

ObjectiveCirculating tumour DNA (ctDNA) is a promising non-invasive biomarker in cancer. We aim to assess the dynamic of ctDNA in patients with hepatocellular carcinoma (HCC).DesignWe analysed 772 plasmas from 173...

Application of serum tumor specific protein 70 for prognostic stratification in acute myeloid leukemia

Objective: To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML). Methods: A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping. Results: Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 (OR=2.54, 95%CI: 1.68-3.84, P<0.001), hemoglobin (HB) (OR=0.96, 95%CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) (OR=1.07, 95%CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95%CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95%CI: 0.890-0.973); C-index=0.925 (95%CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone (Z=1.693,P>0.05). Conclusion: Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.

Regimens and Response Assessment in Minimally Invasive Image-Guided Therapies for Vascular Malformations: Insights from a Large Cohort Study at a Tertiary-Care Hospital

This retrospective study was aimed at characterizing vascular malformations (VMFs) presenting for minimally invasive image-guided therapies (MIT) at a tertiary-care center and evaluating treatment regimens and image-based outcomes using MRI. We analyzed demographic, disease-related, and radiologic features of VMFs presenting to interventional radiology between May 2008 and August 2020 using compendium vascular anomaly (Compva) criteria. MIT and specific agents were evaluated, and treatment effects were assessed through volumetry and mean signal intensity (MSI) on multiparametric longitudinal MRI. The statistics included the paired t-test, ANOVA, and Fisher’s exact test. The cohort included 217 patients (mean age 30 ± 18.4 years; 134 female). Venous malformations were most common (47%). VMFs were frequently located in the head-neck region (23.5%), legs (23.04%), and arms (13.8%). Among 112 treatments, sclerotherapy was performed most frequently (63.9%), followed by embolization (19.3%). MRI showed a significant reduction in T2 MSI for venous (1107.95 vs. 465.26; p = 0.028) and decreased contrast media uptake for lymphatic malformations (557.33 vs. 285.33; p = 0.029) after sclerotherapy, while the lesion volumes did not change significantly (p = 0.8). These findings propose MRI-derived MSI as a potential non-invasive biomarker for assessing the response of VMF to MIT. By leveraging MRI, this study addresses challenges in managing rare diseases like VMFs, while advocating for standardized approaches and prospective studies to better link imaging findings with clinical outcomes.