Biomarkers For Early Diagnosis Research Articles

Discovery of the potential biomarkers for early diagnosis of endometrial cancer via integrating metabolomics and transcriptomics

Endometrial cancer (EC) is one of the most common malignant tumors in women, and the increasing incidence and mortality pose a serious threat to the public health. Early diagnosis of EC could prolong the survival period and optimize the survivorship, greatly alleviating patients’ suffering and social medical pressure. In this study, we collected urine and serum samples from the recruited patients, analyzed the samples using LC-MS approach, and identified the differential metabolites through metabolomic analysis. Then, the differentially expressed genes were identified through the systematic transcriptomic analysis of EC-related dataset from Gene Expression Omnibus (GEO), followed by network profiling of metabolic-reaction-enzyme-gene. In this experiment, a total of 83 differential metabolites and 19 hub genes were discovered, of which 10 different metabolites and 3 hub genes were further evaluated as more potential biomarkers based on network analysis. According to the KEGG enrichment analysis, the potential biomarkers and gene-encoded proteins were found to be involved in the arginine and proline metabolism, histidine metabolism, and pyrimidine metabolism, which was of significance for the early diagnosis of EC. In particular, the combination of metabolites (histamine, 1-methylhistamine, and methylimidazole acetaldehyde) as well as the combination of RRM2, TYMS and TK1 exerted more accurate discrimination abilities between EC and healthy groups, providing more criteria for the early diagnosis of EC.

Gene expression analysis in plasma of patients with Alzheimer's disease

Alzheimer's disease (AD), which is a neurodegenerative disease, cannot be noticed until severe symptoms are observed. This poses a global challenge as the average human lifespan increases, making it a concern for the entire world population. Early diagnosis can play a crucial role in slowing the progression of the disease, thereby enhancing the quality of life for both the patient and their relatives. AD has been linked to alterations in mRNA expressions. The objective of the presented study was to determine whether there were significant differences in gene expression in blood plasma between Alzheimer's patients and healthy controls. MAPT, APP, Tubb3, TrkB, and CDC42 genes were selected as target genes due to their potential associations with AD. To analyse mRNA expression levels in the control group and AD patients, the real-time PCR (qPCR) method was performed. The findings indicate that MAPT, APP, Tubb3, and CDC42 genes' expression levels were significantly downregulated by 1.09, 1.08, 1.09, and 1.14 times, respectively (p<0.05) in AD patients. Although the TrkB gene expression appeared to be downregulated by 1.03 times in the AD group, it is not statistically different. Given the molecular associations between the pathways of the target genes and AD, changes in the expression of these genes may contribute to the pathogenesis of AD. They may represent potential biomarkers for early diagnosis.

Abstract 2451: Investigation of SIRT6 usefulness as a novel biomarker for oral cancer

Abstract Introduction: SIRT6 is one of the seven human sirtuin genes and is known to function as an onco-suppressor gene in colorectal and ovarian cancers, although it is up-regulated in other cancers. Thus, SIRT6 is considered performing both tumor-suppressing and promoting roles. However, the association of SIRT6 with oral squamous cell carcinoma (OSCC) and its role in OSCC pathogenesis are currently unclear. Currently, SCC or CYFRA are used as a tumor marker to assist in the diagnosis of OSCC in a clinical setting whereas its sensitivity is low. Therefor the development of a novel biomarker for early diagnosis and identification of new therapeutic targets is critical to resolve the pressing clinical issues related to the management of OSCC. This study aimed to investigate the expression and the relevance of SIRT6 in patients with OSCC and its potential as a biomarker for early detection and prognosis prediction. Materials and Methods: This study enrolled 78 patients with OSCC and 9 patients with carcinoma in situ (CIS). The OSCC patients had undergone surgery or chemoradiotherapy (51 surgery and 27 chemoradiotherapy). The CIS patients had undergone surgery. Samples were also obtained from 10 patients with oral potentially malignant disorders (OPMDs). Biopsied or surgical resected samples were used for the study. We obtained 21 noncancerous tissues as normal tissues from the adjacent noncancerous tissues after tumor resection. Immunohistochemistry, quantitative real-time RT-PCR, and microarray analyses were performed to determine SIRT6 expression and its association with clinicopathological features in OSCC, CIS, and OPMDs using clinical paraffin embedded specimens. Results: SIRT6 mRNA levels were higher in OSCC tissues than those in noncancerous tissues (p<0.05). And SIRT6 protein expression levels were higher in OSCC, CIS and OPMDs tissues than those in noncancerous tissues (p<0.05). SIRT6 expression was predominant in patients aged ≥65 years and significantly correlated with shorten overall survival. In the microarray analysis, some SIRT6-associated genes, such as ANXA2 was significantly up-regulated, and PIGC and RGPD4 were down-regulated in OSCC. Conclusion: SIRT6 plays a role in tumor homeostasis, leading to a poor prognosis in OSCC. SIRT6 may represent a novel target not only for the treatment, but also as a prognostic marker in OSCC. Citation Format: Haruka Yoshii, Ami Shimoda, Kenji Mitsudo, Mitomu Kioi. Investigation of SIRT6 usefulness as a novel biomarker for oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2451.

Abstract 6090: Integration of innate and adaptive immune signatures for early detection of cancer

Abstract Up to 50% of cancer patients are diagnosed at a late stage with tumors that are often unresectable, leading to intensive treatments and a preventable loss of life. Whilst multiple assays have been developed to tackle the issue of disease mortality, these approaches have serious limitations. For example, circulating tumor DNA (ctDNA) preferentially detects hard-to-treat tumors and micrometastatic disease, with limited sensitivity and specificity for early-stage malignancy, underscoring an urgent need for novel early detection strategies. Substantial evidence exists to demonstrate that signals related to innate (e.g. pro-inflammatory cytokines) and adaptive (e.g. antibodies and T cell receptors [TCRs]) immune engagement arise early in the development of cancer. The immune system therefore offers potential as an exquisitely sensitive and highly specific intrinsic early detection system for cancer. Here we propose the development of a pan-cancer novel early detection assay, using peripheral blood to measure three key cancer-specific components of the anti-tumor immune response: i) T cell receptor (TCR) sequences, ii) antibody signatures, iii) cytokine markers. Our preliminary data demonstrates that an age and smoking-matched cohort of lung cancer patients can be distinguished from healthy donors using TCR sequencing data processed through a published machine learning approach (p<0.01). In support of this, a pilot study on a custom peptide microarray comprised of lung cancer associated antigens and recurrent neoantigens demonstrated that lung cancer patient samples show significantly higher antibody intensities than healthy donors. Thirdly, using data from a prospective cohort study, we have demonstrated that inflammatory markers can be leveraged to predict future cancer diagnosis, and identified key protein markers for future work. These data provide proof-of-principle for the use of these analytes as a tool for early detection. We are actively curating a unique cohort of samples for this work from a prospective study, Nodule Immunophenotyping Biomarker for Lung Cancer Early Diagnosis (NIMBLE) (NCT05432739), which recruits patients with indeterminate lung nodules that may represent early cancers (>280 patients to date). This malignancy has high mortality rates and a significant need for early detection strategies. Through this, we aim to understand the early immunobiological response to cancer and leverage this information to design a novel multi-parametric immunopredictor assay for early detection of cancer. Citation Format: Evelyn Fitzsimons, Alexander Coulton, Hongchang Fu, Marcellus Augustine, Richard Lee, James Reading, Kevin Litchfield. Integration of innate and adaptive immune signatures for early detection of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6090.

Novel serum protein biomarker panel for early diagnosis of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Late presentation of disease at the time of diagnosis is one of the major reasons for dismal prognostic outcomes for PDAC patients. Currently, there is a lack of clinical biomarkers, which can be used to diagnose PDAC patients at an early resectable stage. This study performed proteomic mass spectrometry to identify novel blood-based biomarkers for early diagnosis of PDAC. Serum specimens from 88 PDAC patients and 88 healthy controls (60 discovery cohort and 28 validation cohort) were analyzed using data independent acquisition high resolution mass spectrometry to identify candidate biomarker proteins. A total of 249 proteins were identified and quantified by the mass spectrometric analysis. Six proteins were markedly (>1.5 fold) and significantly (p < .05; q < 0.1) increased in PDAC patients compared to healthy controls in discovery cohort. Notably, four of these six proteins were significantly upregulated in an independent validation cohort. The top three upregulated proteins (i.e., Polymeric Immunoglobulin Receptor [PIGR], von Willebrand Factor [vWF], and Fibrinogen) were validated using enzyme linked immunosorbent assay, which led to selection of PIGR and vWF as a diagnostic biomarker panel for PDAC. The panel showed high ability to diagnose early stage (stage I and II) PDAC patients (area under the curve [AUC]: 0.8926), which was further improved after the addition of clinically used prognostic biomarker (Ca 19-9) to the panel (AUC: 0.9798). In conclusion, a novel serum protein biomarker panel for early diagnosis of PDAC was identified.

Pediatric perforated appendicitis diagnosis based on the C-reactive protein/prealbumin ratio

Pediatric perforated appendicitis, prone to multiple complications, necessitates identifying potential serum biomarkers for early diagnosis and intervention. A cross-sectional study was conducted on patients under 16 with acute appendicitis, admitted to Hainan Women and Children’s Medical Center from January 2019 to July 2023. The patients were categorized into perforated and non-perforated groups. Among the 313 included patients, 106 (33.87%, 95% CI 28.59–39.14%) developed perforation. The C-reactive protein to prealbumin ratio (CPA) showed a significant difference between the perforated and non-perforated groups [6.63 (2.9–13.02) vs. 0.7 (0.11–2.18), p < 0.001]. The AUC of CPA on the ROC curve was 0.691 (95% CI 0.513–0.869, p = 0.084) in patients under 4. In patients aged 4–9, the sensitivity of CPA > 3 predicting perforation was 76.2%, with a specificity of 81.6%, and an AUC of 0.816 (95% CI 0.747–0.886, p < 0.001). For patients aged 9–16, the sensitivity of CPA > 2.2 predicting perforation was 85%, with a specificity of 85.7%, and an AUC of 0.919 (95% CI 0.859–0.979, p < 0.001). CPA > 3 and CPA > 2.2 can predict perforated appendicitis in patients aged 4–9 and 9–16, respectively.

Screening drug-induced liver injury through two independent parameters of lipid droplets and peroxynitrite with a π-extended coumarin-based NIR fluorescent probe

Drug-induced liver injury (DILI) or hepatotoxicity is a significant concern for public health. However, relying on a single biomarker for early DILI diagnosis poses a high risk of false positives. In this study, we reported a near-infrared fluorescent probe (BCOU-S), which enables independent visualization of LDs status and ONOO fluctuations. BCOU-S was constructed by combining a π-extended coumarin core as the NIR fluorophore and a methyl thioether group as the ONOO recognition site. BCOU-S could emit 655 nm NIR fluorescence excited at 518 nm, with a low detection limit of 27 nM and a large Stokes shift of 137 nm. The response mechanism to ONOO was confirmed by molecular orbital density function theory (DFT) and time-dependent DFT (TD-DFT) calculations. BCOU-S monitors LDs status through co-localization, oleic acid (OA) incubation, and starvation induction experiments. It sensitively distinguishes subtle changes in ONOO induced by different drugs in DILI cell models. In the acetaminophen (APAP)-induced DILI model, BCOU-S reveals significant LDs accumulation and increase in ONOO levels, establishing a clear time-effect and dose-effect relationship. Simultaneously monitoring ONOO levels and LDs accumulation, BCOU-S proves to be a more sensitive and effective tool for early DILI prevention, effectively avoiding false positives caused by changes in a single parameter. BCOU-S is a useful tool for further monitoring early DILI development.

Quantification of COX-2 Level in Alzheimer's Disease Patients to Develop Potential Blood-Based Biomarker for Early Diagnosis and Therapeutic Target.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and symptoms develop gradually over many years. The current direction for medication development in AD is focused on neuro-inflammation and oxidative stress. Amyloid-β (Aβ) deposition activates microglia leading to neuro-inflammation and neurodegeneration induced by activation of COX-2 via NFκB p50 in glioblastoma cells. The study aimed to evaluate the concentration of COX-2 and NFκB p50 in serum of AD, mild cognitive impairment (MCI), and geriatric control (GC) and to establish a blood-based biomarker for early diagnosis and its therapeutic implications. Proteins and their mRNA level in blood of study groups were measured by surface plasmon resonance (SPR) and quantitative polymerase chain reaction (qPCR), respectively. The level of protein was further validated by western blot. The binding study of designed peptide against COX-2 by molecular docking was verified by SPR. The rescue of neurotoxicity by peptide was also checked by MTT assay on SH-SY5Y cells (neuroblastoma cell line). Proteins and mRNA were highly expressed in AD and MCI compared to GC. However, COX-2 decreases with disease duration. The peptide showed binding affinity with COX-2 with low dissociation constant in SPR and rescued the neurotoxicity of SH-SY5Y cells by decreasing the level of Aβ, tau, and pTau proteins. It can be concluded that COX-2 protein can serve as a potential blood-based biomarker for early detection and can be a good platform for therapeutic intervention for AD.

Transcriptome profiling and analysis of patients with esophageal squamous cell carcinoma from Kazakhstan.

Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in Central Asia, often diagnosed at advanced stages. Understanding population-specific patterns of ESCC is crucial for tailored treatments. This study aimed to unravel ESCC's genetic basis in Kazakhstani patients and identify potential biomarkers for early diagnosis and targeted therapies. ESCC patients from Kazakhstan were studied. We analyzed histological subtypes and conducted in-depth transcriptome sequencing. Differential gene expression analysis was performed, and significantly dysregulated pathways were identified using KEGG pathway analysis (p-value < 0.05). Protein-protein interaction networks were constructed to elucidate key modules and their functions. Among Kazakhstani patients, ESCC with moderate dysplasia was the most prevalent subtype. We identified 42 significantly upregulated and two significantly downregulated KEGG pathways, highlighting molecular mechanisms driving ESCC pathogenesis. Immune-related pathways, such as viral protein interaction with cytokines, rheumatoid arthritis, and oxidative phosphorylation, were elevated, suggesting immune system involvement. Conversely, downregulated pathways were associated with extracellular matrix degradation, crucial in cancer invasion and metastasis. Protein-protein interaction network analysis revealed four distinct modules with specific functions, implicating pathways in esophageal cancer development. High-throughput transcriptome sequencing elucidated critical molecular pathways underlying esophageal carcinogenesis in Kazakhstani patients. Insights into dysregulated pathways offer potential for early diagnosis and precision treatment strategies for ESCC. Understanding population-specific patterns is essential for personalized approaches to ESCC management.

MicroRNAs as Potential Biomarkers for the Diagnosis, Treatment, and Prognosis of Sexually Transmitted Diseases: Recent Advances and Future Directions

Sexually transmitted diseases (STDs), including condyloma acuminatum (CA), syphilis, gonorrhea, genital Chlamydia trachomatis (CT), and acquired immune deficiency syndrome (AIDS)/human immunodeficiency virus (HIV) infection, are a group of diseases primarily transmitted through sexual contact, similar behaviors, and indirect contact. These diseases exert a profound impact on both the physical and mental health of patients and impose a substantial socioeconomic burden. Nonetheless, there is a lack of satisfactory treatment options and preventive strategies currently. Research has revealed aberrant expression patterns of microRNAs (miRNAs) in the tissues and blood of individuals with STDs, which are involved in the regulation of essential cellular processes, including proliferation, differentiation, and apoptosis. Consequently, miRNAs hold promise as crucial biomarkers for early diagnosis, disease assessment, prognosis, and potential therapeutic targets for STDs. This systematic review presents pertinent research on miRNAs in the context of STDs to establish a theoretical foundation for clinical diagnosis and treatment strategies.

Mitochondrial Metabolism in Major Depressive Disorder: From Early Diagnosis to Emerging Treatment Options.

Major Depressive Disorder (MDD) is one of the most disabling diseases in the world. MDD is traditionally diagnosed based on a patient's symptoms, which can lead to misdiagnosis. Although the pathogenic mechanisms of MDD are unknown, several studies have identified mitochondrial dysfunction as a central factor in the onset and progression of MDD. In the context of MDD, alterations in mitochondrial metabolism can lead to imbalances in energy production and oxidative stress, contributing to the disorder´s underlying pathophysiological mechanisms. Consequently, the identification of mitochondrial dysfunction as a key biomarker for early and accurate diagnosis of MDD represents a significant challenge. Faced with the limits of traditional treatments with antidepressants, new pharmacological therapeutic targets are being investigated such as ketamine/esketamine, psychedelics, or anti-inflammatories. All of these drugs show potential antidepressant effects due to their speed of action and ability to modulate neuroplasticity and/or motor processing. In parallel, non-pharmacological therapeutic targets are studied, like Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS), recognized for their ability to modulate neuronal activity and offer treatment alternatives. As cellular activity is directly related to mitochondrial respiration, the aim of this review is examining the link between mitochondrial dysfunction and MDD, assessing how mitochondrial biomarkers could provide a more objective and precise diagnostic tool, and exploring other treatments in addition to traditional antidepressants, with a specific focus on emerging therapeutic targets. Finally, a detailed analysis of the strengths, weaknesses, opportunities, and threats of these approaches was carried out, highlighting the key challenges that must be addressed.

Novel electrochemical platform based on C3N4-graphene composite for the detection of neuron-specific enolase as a biomarker for lung cancer

Lung cancer remains the leading cause of cancer mortality worldwide. Small cell lung cancer (SCLC) accounts for 10–15% of cases and has an overall 5-years survival rate of only 15%. Neuron-specific enolase (NSE) has been identified as a useful biomarker for early SCLC diagnosis and therapeutic monitoring. This work reports an electrochemical immunosensing platform based on a graphene-graphitic carbon nitride (g-C3N4) nanocomposite for ultrasensitive NSE detection. The g-C3N4 nanosheets and graphene nanosheets were synthesized via liquid exfoliation and integrated through self-assembly to form the nanocomposite. This nanocomposite was used to modify screen-printed carbon electrodes followed by covalent immobilization of anti-NSE antibodies. The unique properties of the graphene-g-C3N4 composite facilitated efficient antibody loading while also enhancing electron transfer efficiency and electrochemical response. Systematic optimization of experimental parameters was performed. The immunosensor exhibited a wide linear detection range of 10 pg/mL to 100 ng/mL and low limit of detection of 3 pg/mL for NSE along with excellent selectivity against interferences. Real serum matrix analysis validated the applicability of the developed platform for sensitive and accurate NSE quantifica-tion at clinically relevant levels. This novel graphene-g-C3N4 nanocomposite based electro-chemical immunoassay demonstrates great promise for early diagnosis of SCLC.

Metabolomics profiling for diagnosis of acute renal failure after cardiopulmonary bypass.

Acute renal failure (ARF) is one of the most serious complications of cardiopulmonary bypass (CPB) surgery. Serum creatinine level is a key compound examined to understand whether renal function is normal. However, its level may vary based on age, gender, race, muscle mass, nutrition, and drugs taken by an individual. In addition, it may not be detected without a 50% reduction in renal function and may lead to delays in treatment. New markers are needed for early diagnosis of ARF. They were determined for early diagnosis of ARF after CPB. Metabolic differences in plasma samples of individuals who developed and did not develop ARF after cardiopulmonary bypass were determined. This study was the first to perform an untargeted metabolomics analysis for early diagnosis of ARF after CPB surgery. Plasma samples were taken from 105 patients (9 ARF patients) at five time points to identify the time at which a more accurate ARF diagnosis can be made. A total of 687 samples, including quality control samples, were analyzed. Two hundred twenty-six metabolites were identified using retention index libraries. Based on the statistical evaluations, tryptophan, threonine, and methionine were found in lower concentrations in patients with ARF compared to the control group at all time points. Whereas gluconic acid, hypoxanthine, and lactic acid showed a decreasing trend over time, longitudinal analysis showed that cysteine, hippuric acid, and uric acid levels increased over time in the ARF group. These metabolites are candidate biomarkers for early diagnosis of ARF as well as biomarkers for tracking the recovery of ARF patients.

Purine salvage–associated metabolites as biomarkers for early diagnosis of esophageal squamous cell carcinoma: a diagnostic model–based study

Esophageal squamous cell carcinoma (ESCC) remains an important health concern in developing countries. Patients with advanced ESCC have a poor prognosis and survival rate, and achieving early diagnosis remains a challenge. Metabolic biomarkers are gradually gaining attention as early diagnostic biomarkers. Hence, this multicenter study comprehensively evaluated metabolism dysregulation in ESCC through an integrated research strategy to identify key metabolite biomarkers of ESCC. First, the metabolic profiles were examined in tissue and serum samples from the discovery cohort (n = 162; ESCC patients, n = 81; healthy volunteers, n = 81), and ESCC tissue-induced metabolite alterations were observed in the serum. Afterward, RNA sequencing of tissue samples (n = 46) was performed, followed by an integrated analysis of metabolomics and transcriptomics. The potential biomarkers for ESCC were further identified by censoring gene-metabolite regulatory networks. The diagnostic value of the identified biomarkers was validated in a validation cohort (n = 220), and the biological function was verified. A total of 457 dysregulated metabolites were identified in the serum, of which 36 were induced by tumor tissues. The integrated analyses revealed significant alterations in the purine salvage pathway, wherein the abundance of hypoxanthine/xanthine exhibited a positive correlation with HPRT1 expression and tumor size. A diagnostic model was developed using two purine salvage–associated metabolites. This model could accurately discriminate patients with ESCC from normal individuals, with an area under the curve (AUC) (95% confidence interval (CI): 0.680–0.843) of 0.765 in the external cohort. Hypoxanthine and HPRT1 exerted a synergistic effect in terms of promoting ESCC progression. These findings are anticipated to provide valuable support in developing novel diagnostic approaches for early ESCC and enhance our comprehension of the metabolic mechanisms underlying this disease.

Downregulation of salivary miR-3928 as a potential biomarker in patients withoral squamous cell carcinoma and oral lichen planus.

Recent studies highlighted the role of miR expressed in saliva as reliable diagnostic and prognostic tools in the long-term monitoring of cancer processes such as oral squamous carcinoma (OSCC). Based on a few previous studies, it seems the miR-3928 can be considered a master regulator in carcinogenesis, and it can be therapeutically exploited. This is the first study that compared oralpotentially malignant disorder (OLP) and malignant (OSCC) lesions for miR-3928 expression. In this cross-sectional study, saliva samples from 30 healthy control individuals, 30 patients with erosive/atrophic oral lichen planus, and 31 patientswithOSCCwere collected. The evaluation of miR-3928 expression by q-PCR and its correlation with clinicopathological indices were analyzed by Shapiro-Wilk, Kruskal-Wallis, Pearson'sχ2 , and Mann-Whitney tests. The p-value less than .05 indicated statistically significant results. Based on nonparametric Kruskal-Wallis test results, there was a statistically significant difference between the ages of three study groups (p < .05). This test demonstrated a statistically significant difference between the average of miR-3928 expression in three study groups (p < .05). The result of the χ2 test showed a statistically significant difference in miR-3928 expression between patients withOLP(p = .01)and alsopatients withOSCC (p < .0001)in comparison to the control group. The salivary miR-3928 can play a tumor suppressive role in the pathobiology of OSCC, and it is significantly downregulated in patients. According to the potential tumor suppressive role of miR-3928 in the OSCC process, we can consider this microRNA as a biomarker for future early diagnosis, screening, and potential target therapy.

Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson’s disease

Parkinson’s disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis, prognosis prediction, or monitoring therapeutic response. This lack of biomarkers greatly impedes patient care and translational research—l-DOPA remains the standard of care more than 50 years after its introduction. Here, we performed a large-scale, multi-tissue, and multi-platform proteomics study to identify new biomarkers for early diagnosis and disease monitoring in PD. We analyzed 4877 cerebrospinal fluid, blood plasma, and urine samples from participants across seven cohorts using three orthogonal proteomics methods: Olink proximity extension assay, SomaScan aptamer precipitation assay, and liquid chromatography–mass spectrometry proteomics. We discovered that hundreds of proteins were upregulated in the CSF, blood, or urine of PD patients, prodromal PD patients with DAT deficit and REM sleep behavior disorder or anosmia, and non-manifesting genetic carriers of LRRK2 and GBA mutations. We nominate multiple novel hits across our analyses as promising markers of early PD, including DOPA decarboxylase (DDC), also known as l-aromatic acid decarboxylase (AADC), sulfatase-modifying factor 1 (SUMF1), dipeptidyl peptidase 2/7 (DPP7), glutamyl aminopeptidase (ENPEP), WAP four-disulfide core domain 2 (WFDC2), and others. DDC, which catalyzes the final step in dopamine synthesis, particularly stands out as a novel hit with a compelling mechanistic link to PD pathogenesis. DDC is consistently upregulated in the CSF and urine of treatment-naïve PD, prodromal PD, and GBA or LRRK2 carrier participants by all three proteomics methods. We show that CSF DDC levels correlate with clinical symptom severity in treatment-naïve PD patients and can be used to accurately diagnose PD and prodromal PD. This suggests that urine and CSF DDC could be a promising diagnostic and prognostic marker with utility in both clinical care and translational research.

Auditory Steady-State Evoked Potentials in Post Traumatic Stress Disorder: Introduction of a Potential Biomarker.

Objective: The lack of steady-state evoked potential (SSEP) studies on post-traumatic stress disorder (PTSD) has led to undiscovered useful information about the pathophysiology of the disorder. Thus, we explored SSEP patterns in PTSD patients during a stop-signal task to disclose possible impairments in these informative brain potentials. Method : 25 adult patients with PTSD and 25 healthy adults participated in this research. Subjects were assessed with electroencephalography while the tone signal stimuli at 40 Hz were used to evoke SSEPs and subjects performed a stop-signal task. The amplitude and phase of SSEPs were then computed in different brain regions. The subjects were also evaluated using the Mississippi PTSD questionnaire. Appropriate statistical methods such as repeated measure ANOVA were used to compare the two groups, and the correlation between SSEPs and clinical symptoms was assessed using Pearson correlation analysis. Results: Patients showed considerably poorer performance in the cognitive task (P < 0.01), accompanied by raised SSEP phase and amplitude in the anterior and midline regions compared to healthy controls (P < 0.05). The Mississippi total score was positively correlated with the SSEP amplitude in the midline region (r = 0.62, P < 0.05). Furthermore, based on ROC analysis, the SSEP amplitude in the midline region provided an excellent AUC value (AUC = 0.850) for distinguishing patients with PTSD from normal subjects. Conclusion: Current findings suggest that abnormalities in the anterior and midline cortical neural networks are involved in the pathophysiology of PTSD. Importantly, midline abnormalities may provide a clinically-relevant measure for researchers wishing to assess the use of biomarkers for early diagnosis of PTSD as well as to evaluate new therapeutic and management approaches in the treatment of PTSD.

SCancerRNA: Expression at the Single-cell Level and Interaction Resource of Non-coding RNA Biomarkers for Cancers.

Non-coding RNAs (ncRNAs) participate in multiple biological processes associated with cancers as tumor suppressors or oncogenic drivers. Due to their high stability in plasma, urine, and many other fluids, ncRNAs have the potential to serve as key biomarkers for early diagnosis and screening of cancers. During cancer progression, tumor heterogeneity plays a crucial role, and it is particularly important to understand the gene expression patterns of individual cells. With the development of single-cell RNA sequencing (scRNA-seq) technologies, uncovering gene expression in different cell types for human cancers has become feasible by profiling transcriptomes at the cellular level. However, a well-organized and comprehensive online resource that provides access to the expression of genes corresponding to ncRNA biomarkers in different cell types at the single-cell level is not available yet. Therefore, we developed the SCancerRNA database to summarize experimentally supported data on long ncRNA, microRNA, PIWI-interacting RNA, small nucleolar RNA, and circular RNA biomarkers, as well as data on their differential expression at the cellular level. Furthermore, we collected biological functions and clinical applications of biomarkers to facilitate the application of ncRNA biomarkers to cancer diagnosis, as well as the monitoring of progression and targeted therapies. SCancerRNA also allows users to explore interaction networks of different types of ncRNAs, and build computational models in the future. SCancerRNA is freely accessible at http://www.scancerrna.com/BioMarker.

NcRS: A resource of non-coding RNAs in sepsis

Sepsis, a life-threatening condition triggered by the body's response to infection, presents a significant global healthcare challenge characterized by disarrayed host responses, widespread inflammation, organ impairment, and heightened mortality rates. This study introduces the ncRS database (http://www.ncrdb.cn), a meticulously curated repository housing 1144 experimentally validated non-coding RNAs (ncRNAs) intricately linked with sepsis. ncRS offers comprehensive RNA data, exhaustive experimental insights, and integrated annotations from diverse databases. This resource empowers researchers and clinicians to decipher ncRNAs' roles in sepsis pathogenesis, potentially identifying vital biomarkers for early diagnosis and prognosis, thus facilitating personalized treatments.

Complete Blood Count in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic disease that affects the central nervous system in primarily young adults. Although the exact etiology of MS is unknown, autoimmune mechanisms are thought to play a crucial role, especially with CD4+ T cells involved in the immune response. Inflammatory reactions involving T cells and macrophages are commonly observed in MS lesions. B lymphocytes, plasma cells, and antibodies also contribute to MS pathogenesis. Neutrophils, lymphocytes, monocytes, and platelets, key immune system components, play roles in inflammatory processes, but their association with MS prognosis remains inconclusive. Due to its heterogeneous nature, clinical manifestations of MS vary depending on the location of the affected central nervous system. While several potential biomarkers have been identified for MS diagnosis and monitoring, none have been universally accepted. Studies have examined complete blood count parameters in MS patients, including erythrocyte, platelet, and leukocyte populations. Changes in these parameters have been observed in MS patients compared to healthy controls and may be related to disease prognosis. For example, increased erythrocyte fragility and altered hemoglobin levels have been reported in MS patients. Leukocyte counts and ratios, such as the neutrophil/lymphocyte ratio, have shown associations with disease severity. Platelet activation and interaction with immune cells have also been implicated in MS pathophysiology. Nevertheless, further research is needed to fully understand the role of complete blood count parameters in MS. Identifying reliable biomarkers for early diagnosis and prognosis prediction would greatly enhance MS management. Moreover, these benefits could lead to substantial improvements in achieving complete recovery of patients, surpassing the focus on current symptomatic treatments.