Diagnostic Marker In Patients Research Articles

Role of microRNA-363 during tumor progression and invasion.

Recent progresses in diagnostic and therapeutic methods have significantly improved prognosis in cancer patients. However, cancer is still considered as one of the main causes of human deaths in the world. Late diagnosis in advanced tumor stages can reduce the effectiveness of treatment methods and increase mortality rate of cancer patients. Therefore, investigating the molecular mechanisms of tumor progression can help to introduce the early diagnostic markers in these patients. MicroRNA (miRNAs) has an important role in regulation of pathophysiological cellular processes. Due to their high stability in body fluids, they are always used as the non-invasive markers in cancer patients. Since, miR-363 deregulation has been reported in a wide range of cancers, we discussed the role of miR-363 during tumor progression and metastasis. It has been reported that miR-363 has mainly a tumor suppressor function through the regulation of transcription factors, apoptosis, cell cycle, and structural proteins. MiR-363 also affected the tumor progression via regulation of various signaling pathways such as WNT, MAPK, TGF-β, NOTCH, and PI3K/AKT. Therefore, miR-363 can be introduced as a probable therapeutic target as well as a non-invasive diagnostic marker in cancer patients.

Transcriptomic analysis identifies the shared diagnostic biomarkers and immune relationship between Atherosclerosis and abdominal aortic aneurysm based on fatty acid metabolism gene set.

Epidemiological research has demonstrated that there is a connection between lipid metabolism disorder and an increased risk of developing arteriosclerosis (AS) and abdominal aortic aneurysm (AAA). However, the precise relationship between lipid metabolism, AS, and AAA is still not fully understood. The objective of this study was to examine the pathways and potential fatty acid metabolism-related genes (FRGs) that are shared between AS and AAA. AS- and AAA-associated datasets were retrieved from the Gene Expression Omnibus (GEO) database, and the limma package was utilized to identify differentially expressed FRGs (DFRGs) common to both AS and AAA patients. Functional enrichment analysis was conducted on the (DFRGs), and a protein-protein interaction (PPI) network was established. The selection of signature genes was performed through the utilization of least absolute shrinkage and selection operator (LASSO) regression and random forest (RF). Subsequently, a nomogram was developed using the results of the screening process, and the crucial genes were validated in two separate external datasets (GSE28829 and GSE17901) as well as clinical samples. In the end, single-sample gene set enrichment analysis (ssGSEA) was utilized to assess the immune cell patterns in both AS and AAA. Additionally, the correlation between key crosstalk genes and immune cell was evaluated. In comparison to control group, both AS and AAA patients exhibited a decrease in fatty acid metabolism score. We found 40 DFRGs overlapping in AS and AAA, with lipid and amino acid metabolism critical in their pathogenesis. PCBD1, ACADL, MGLL, BCKDHB, and IDH3G were identified as signature genes connecting AS and AAA. Their expression levels were confirmed in validation datasets and clinical samples. The analysis of immune infiltration showed that neutrophils, NK CD56dim cells, and Tem cells are important in AS and AAA development. Correlation analysis suggested that these signature genes may be involved in immune cell infiltration. The fatty acid metabolism pathway appears to be linked to the development of both AS and AAA. Furthermore, PCBD1, ACADL, MGLL, BCKDHB, and IDH3G have the potential to serve as diagnostic markers for patients with AS complicated by AAA.

Factors Influencing Early Diagnosis and Poor Prognosis of Dysphagia After Senile Ischemic Stroke.

Dysphagia is often a long-term problem after ischemic stroke, which are often accompanied by complications and results in poor outcome. This study aimed to investigate the influencing factors associated with the prognosis of dysphagia after senile ischemic stroke and evaluate the diagnostic performance of crucial factors. A total of 192 elderly ischemic stroke patients (96 patients without dysphagia with average age of 69.81 ± 4.61years and 96 patients with dysphagia with average of 70.00 ± 6.66years) were enrolled in the retrospective study. The clinical factors of the patients were collected and recorded for chi-square analysis and logistic analysis. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance of international normalized ratio (INR) and homocysteine (Hcy) in senile ischemic stroke patients. The age, cough reflex, history of stroke, mechanical ventilation, eating posture, insufficient elevation of the larynx, standard swallowing assessment (SSA) score, Hcy value, and INR were closely related to endpoint events of patients with dysphagia. The joint model (combined INR and Hcy value) can increase the area under the curve (AUC) value (0.948) with higher sensitivity and specificity for predicting patients with dysphagia occurred endpoint events.The influencing factors for older ischemic stroke patients with dysphagia include age, cough reflex, history of stroke, mechanical ventilation, eating posture, insufficient elevation of the larynx, SSA score, Hcy value, and INR. INR and Hcy were independent risk factors for prognosis and diagnostic markers for patients with dysphagia after senile ischemic stroke.

Significance of serum ferritin and De Ritis ratio in non-alcoholic fatty liver disease as diagnostic markers

Objective: To ascertain the significance of serum ferritin and De Ritis ratio as diagnostic markers in patients of non-alcoholic fatty liver disease with and without type 2 diabetes mellitus. Methods: The comparative cross-sectional study was conducted from February to October 2022 at the Radiology Department of Combined Military Hospital, Rawalpindi, Pakistan, and comprised individuals aged 30-65 who were divided into 3 groups. Healthy controls formed group I, non-alcoholic fatty liver disease patients without type 2 diabetes mellitus formed group II and non-alcoholic fatty liver disease patients with type 2 diabetes mellitus were in group III.  Blood 5ml was withdrawn and assessed for alkaline phosphatase, aspartate transaminase, alanine transaminase and ferritin. De Ritis ratio was calculated and subjected to intergroup comparison. Data was analysed using SPSS 22. Results: Of the 210 subjects, 110(52.4%) were males and 100(47.6%) were females, with 70(33.3%) in each of the three groups. Group I had 38(54.3%) females and 32(45.7%) males with mean age 37.50±4.513. In group II, there were 27(38.6%) females and 43(61.4%) males with mean age 45.86±9.646, while in group III there were 35(50%) females and 35(50%) males with mean age 54.01±9.243. Serum ferritin levels were significantly increased in patient groups II and III compared to control group I (p<0.05). De Ritis ratio was markedly raised in groups II and III compared to group I (p<0.05). Ferritin was significantly correlated to age, weight, height, fasting blood sugar, haemoglobin, alkaline phosphatase, aspartate aminotransferase, alanine transaminase and bilirubin (p<0.05). De Ritis ratio had a significant correlation with body mass index and fasting blood sugar (p<0.05). Conclusion: Serum ferritin and De Ritis ratio were found to be useful diagnostic indicators for non-alcoholic fatty liver disease, highlighting their importance in improving disease screening. Key Words: NAFLD, Non-alcoholic steatohepatitis, Ferritin, SGPT, SGOT.

Can Ischemia-Modified Albumin Be a Helpful Marker in the Diagnosis and Follow-Up of Childhood Intussusception?

Intussusception is the invagination of a proximal segment of the intestine into a more distal segment. The present study aimed to determine the sensitivity of the ischemia-modified albumin (IMA) and the correlation between IMA and the severity of intestinal ischemia in intussusception cases. Thirty-six consecutive children aged between 0 and 16 years presenting with the clinical and radiological features of intestinal obstruction caused by intussusception were enrolled in the study. The age- and sex-matched control group was composed of patients undergoing outpatient surgery. The patients were categorized as cases of type I (ileoileal), type II (ileocecal), and type III (colocolic) based on the ultrasonography findings. The mean IMA level of the intussusception group was 179.13 ± 220.33 ng/mL, whereas the mean level was found as 89 ± 70.9 ng/mL in the control group. When the patients were categorized as ileoileal, ileocecal, and colocolic, the mean IMA levels were detected as 235.65 ± 268.14 ng/mL, 174.46 ± 212.8 ng/mL, and 46.95 ± 19.56 ng/mL, respectively. There was a moderate correlation between the invaginated segment lengths measured by the surgeon during the operation and IMA levels. Our study findings reveal that IMA can be used as an auxiliary diagnostic marker in patients presenting with symptoms and signs suggestive of intussusception. Thus, patients can be screened for mechanical bowel obstruction due to intussusception and may be referred to pediatric surgery centers earlier for further examination.

Intrathecal IgM synthesis as a diagnostic marker in patients with suspected CNS lymphoma

AbstractFor CNS lymphomas (CNSL), there is a high need for minimally invasive and easily obtainable diagnostic markers. Intrathecal IgM synthesis can easily be determined in routine CSF diagnostics. The aim of this study was to systematically investigate the diagnostic potential of intrathecal IgM synthesis in primary and secondary CNSL (PCNSL and SCNSL). In this retrospective study, patients with a biopsy‐proven diagnosis of PCNSL or SCNSL were compared with patients with other neurological diseases in whom CNSL was initially the primary radiological differential diagnosis based on MRI. Sensitivity and specificity of intrathecal IgM synthesis were calculated using receiver operating characteristic curves. Seventy patients with CNSL were included (49 PCNSL and 21 SCNSL) and compared to 70 control patients. The sensitivity and specificity for the diagnosis of CNSL were 49% and 87%, respectively, for the entire patient population and 66% and 91% after selection for cases with tumor access to the CSF system and isolated intrathecal IgM synthesis. In cases with MRI‐based radiological suspicion of CNSL, intrathecal IgM synthesis has good specificity but limited sensitivity. Because of its low‐threshold availability, analysis of intrathecal IgM synthesis has the potential to lead to higher diagnostic accuracy, especially in resource‐limited settings, and deserves further study.

Sleep features in alcohol use disorder: A systematic review and meta-analysis of polysomnographic findings in case-control studies

Background and objectivesAlcohol use disorder (AUD) is often linked to sleep problems, but previous studies on sleep abnormalities in AUD have produced inconsistent results. This study aims to provide a comprehensive analysis of objectively measured sleep abnormalities in AUD and determine the impact of related and demographic factors on sleep disturbance. MethodsWe conducted a comprehensive search of several databases from 1968 to 2023 to identify relevant studies. A total of 12 studies, consisting of 13 datasets, were included in the analysis. We extracted information on sleep microarchitecture, as well as demographic and clinical features, from each study. The GRADE approach was used to assess the reliability and strength of the evidence. ResultsPatients with AUD exhibited several sleep abnormalities, including longer sleep onset latency, lower sleep efficiency, increased stage 1 sleep, decreased stage 2 sleep, reduced slow wave sleep, and elevated rapid eye movement (REM) sleep density and first REM minute. The sleep patterns in individuals with AUD were also influenced by factors such as ethnicity, age, gender, and abstinence period. ConclusionsThis study is the largest quantitative assessment of impaired sleep as a diagnostic marker in patients with AUD. Understanding the sleep patterns of individuals with AUD can assist clinicians in developing effective treatment plans for managing sleep-related symptoms associated with AUD.

The Role of the AMH, SHBG and LH/FSH Ratio in the Diagnosis of Polycystic Ovary Syndrome in Adolescent

Objective: Polycystic ovary syndrome (PCOS) diagnosis is controversial in adolescents. Therefore, auxiliary markers are required for the diagnosis of PCOS. We aimed to evaluate whether luteinizing hormone (LH)/ follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), anti-Mullerian hormone (AMH), and sex hormone-binding globulin (SHBG) levels are a useful test to screen adolescents with PCOS and to investigate which of them has more diagnostic value in the PCOS diagnosis. Material and Methods: A total of 56 girls with PCOS and 70 healthy girls consisted in this study. Pediatric Endocrine Society criteria were used to diagnose PCOS. Clinical examinations and hormonal assays were performed. Results: The LH/FSH ratio, and FAI levels were detected significantly higher, and SHBG levels were detected significantly lower in the PCOS group than in the control group (p<0.001). The best marker for PCOS diagnosis was found as AMH. In all adolescents with PCOS, irrespective of obesity/overweight, significantly higher AMH levels were observed compared to the control subjects (p<0.001). Also, we measured a LH/FSH ratio cut-off value of 1.48 ng/ml with 77% sensitivity and 77% specificity to differentiate cases with PCOS from healthy controls. Conclusion: AMH, FAI, and LH/FSH ratio could be usefull and valuable tests for the PCOS diagnosis in the presence of the PCOS criteria. AMH was found to be the strongest diagnostic marker in patients with PCOS.

Clinical Applicability of Tissue Polypeptide Antigen and CA-125 in Gynecological Malignancies.

Nowadays there still is no sufficient screening tool for ovarian and uterine cancer. The current study aimed to investigate whether cancer antigen 125 (CA-125), tissue polypeptide antigen (TPA) or the combination of both markers are able to act as screening tools for ovarian or uterine cancer. A total of 275 blood samples from different cohorts (ovarian cancer, uterine cancer, benign control group) were prospectively drawn and analyzed. Established biomarkers TPA and CA-125 showed elevated serum concentrations in patients with malignant tumors as compared to healthy women and women with benign diseases. In ROC curve analyses, both biomarkers were well able to discriminate between malignant and healthy, benign or overall non-malignant cases in the whole sample, with AUCs of 0.842 and above. While TPA was the best diagnostic marker in patients with uterine cancer, CA 125 was the best in patients with ovarian cancer. TPA and CA-125 both showed promising results for the detection of gynecologic malignancies. The combination of CA-125 and TPA did not improve sensitivity in comparison to single markers.

Biochemical markers of neurodegeneration in patients with cerebral small vessel disease and Alzheimer's disease

Introduction. Cerebral small vessel disease (CSVD) as well as the Alzheimer's disease (AD) and their comorbidities are the most common causes of cognitive impairments (CIs).
 Objective: to evaluate the predictive power of the biochemical neurodegeneration markers in patients with CSVD and AD.
 Materials and methods. We assessed the following neurodegeneration markers in 68 patients with CSVD (61.0 8.6 years; 60.3% males), 17 patients with AD (65.2 8.3 years; 35.3% males), and 26 healthy volunteers (59.9 6.7 years; 38.5% males): neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), neurofilament light polypeptide (NEFL) in blood (for all patients) and in cerebrospinal fluid (CSF; in patients with CSVD and AD). We assessed the predictive power of those markers with ROC analysis.
 Results. As compared to the control group, serum GFAP in patients with CSVD showed its predictive power at 0.155 ng/ml (sensitivity 74%; specificity 70%). Serum NEFL 0.0185 ng/ml (sensitivity 82%; specificity 96%) and NSE 4.95 g/ml (sensitivity 77%; specificity 71%) showed their predictive power in patients with AD. CSF GFAP 1.03 ng/ml (sensitivity 84%; specificity 88%), CSF NSE 19.10 g/ml (sensitivity 88%; specificity 91%), serum NEFL 0.021 ng/ml (sensitivity 71%; specificity 76%), serum NSE /CSF NSE ratio 0.273 ng/ml (sensitivity 87%; specificity 88%) help differentiate CSVD from AD.
 Conclusions. We found that serum GFAP can be a useful diagnostic marker in patients with CSVD, while serum NEFL and serum NSE can help identify the AD. In addition, CSF GFAP and CSF NSE as well as serum NEFL and serum NSE/CSF NSE can help differentiate CSVD from AD. We can use those markers in clinical and research practice to identify the vascular and neurodegenerative causes of CIs and their comorbidities, which is of a great importance in developing specific treatment and predicting the course of the disease.

Study of Clinical Utility of miRNA-31 in Diagnosis of Bladder Cancer in Egyptian Patients

Abstract Background Bladder cancer ranks as one of the most prevalent cancers worldwide, with a rising incidence and prevalence; also it is accompanied by a high morbidity and mortality. BC is a complex disease with several molecular and pathological pathways, thus reflecting different behaviors depending on the clinical staging of the tumor and molecular type. Objective To evaluate the clinical utility of miRNA-31 in plasma as an early novel diagnostic marker for patients with bladder cancer, in comparison to cystoscopy with histopathology as a conventionally used technique for cancer detection. Patients and Methods This study was performed on a total of 45 subjects selected from Urosurgery department at Theodor Bilharz Research Institute (TBRI) and Ain shams university hospitals in the period from January to October 2020. They were divided into the following groups: Group 1: 30 Bladder cancer (BCA) patients diagnosed by clinical examination, laboratory investigations (Urine cytology, urine analysis, complete blood count, liver & kidney functions) & cystoscopy with histopathology. Group 2: 15 apparently healthy volunteers matched in age and sex with the patients taken as the control group. Results It is found that miRNA 31 is abnormally expressed in cancer cells and play an important role in cancer development. It functions as an oncogene or a tumor suppressor in different cancer types which made it a candidate for our study. The present study revealed a statistical significance of miRNA-31 upregulation in plasma of late BC patients in comparison with early BC patients and control group, but there was no significance between its upregulation in the plasma of early BC patients in comparison with the control group. This shows that circulating miRNA-31 in plasma can be used as a prognostic biomarker for BC. Conclusion The present study revealed that the circulating miRNA-31 in plasma has no role as a diagnostic biomarker for BC.

SIX1 Downregulation Suppresses Self-renewal Capacity and THY1 Expression in Hepatocellular Carcinoma and SIX1 Dominate the Survival in Liver Cancer.

Sine oculis homeoprotein 1 exerts an essential role in embryonic development, and it was also identified to be reactivated in various types of mammalian cancer. The sine oculis homeoprotein 1 transcription factor was demonstrated to induce epithelial-mesenchymal transition, regulate crucial genes associated with cancer progression, and increase the oncogenic potential of cells. Therefore, the present study aimed to identify the role of sine oculis homeoprotein 1 in cancer. Sine oculis homeoprotein 1 gene expression was tested with real-time quantitative polymerase chain reaction (PCR) in different cancer types. Sine oculis homeoprotein 1 expression was suppressed by short hairpin RNA transduction in the SNU398 hepatocellular carcinoma cell line. The effects of sine oculis homeoprotein 1 on cell proliferation, drug resistance, and sphere formation were assessed in shSIX1 cells. Immunohistochemical and in silico analyses were performed to determine the prognostic role of sine oculis homeoprotein 1 expression. The upregulated expression levels of sine oculis homeoprotein 1 were revealed to be correlated with the stage of the disease in breast, colon, and liver cancer, with liver cancer exhibiting the highest expression profile. Sine oculis homeoprotein 1 downregulation significantly affected cell proliferation and suppressed sorafenib resistance and sphere-forming ability. Furthermore, sine oculis homeoprotein 1 knockdown cells were identified to have decreased CD90 levels, essential for cancer stem cell properties. Finally, sine oculis homeoprotein 1 expression was a CD90-independent biomarker for the clinical prognosis of liver cancer. The results of this study showed that the knockdown of sine oculis homeoprotein 1 expression might help to prevent hepatocarcinogenesis by increasing drug sensitivity and controlling tumor sphere formation. Overall, these results indicated that sine oculis homeoprotein 1 expression might be useful as a diagnostic marker for patients with hepatocellular carcinoma.

Serum NMR-Based Metabolomics Profiling Identifies Lipoprotein Subfraction Variables and Amino Acid Reshuffling in Myeloma Development and Progression.

Multiple myeloma (MM) is an incurable hematological cancer. It is preceded by monoclonal gammopathy of uncertain significance (MGUS)-an asymptomatic phase. It has been demonstrated that early detection increases the 5-year survival rate. However, blood-based biomarkers that enable early disease detection are lacking. Metabolomic and lipoprotein subfraction variable profiling is gaining traction to expand our understanding of disease states and, more specifically, for identifying diagnostic markers in patients with hematological cancers. This study aims to enhance our understanding of multiple myeloma (MM) and identify candidate metabolites, allowing for a more effective preventative treatment. Serum was collected from 25 healthy controls, 20 patients with MGUS, and 30 patients with MM. 1H-NMR (Nuclear Magnetic Resonance) spectroscopy was utilized to evaluate serum samples. The metabolite concentrations were examined using multivariate, univariate, and pathway analysis. Metabolic profiles of the MGUS patients revealed lower levels of alanine, lysine, leucine but higher levels of formic acid when compared to controls. However, metabolic profiling of MM patients, compared to controls, exhibited decreased levels of total Apolipoprotein-A1, HDL-4 Apolipoprotein-A1, HDL-4 Apolipoprotein-A2, HDL Free Cholesterol, HDL-3 Cholesterol and HDL-4 Cholesterol. Lastly, metabolic comparison between MGUS to MM patients primarily indicated alterations in lipoproteins levels: Total Cholesterol, HDL Cholesterol, HDL Free Cholesterol, Total Apolipoprotein-A1, HDL Apolipoprotein-A1, HDL-4 Apolipoprotein-A1 and HDL-4 Phospholipids. This study provides novel insights into the serum metabolic and lipoprotein subfraction changes in patients as they progress from a healthy state to MGUS to MM, which may allow for earlier clinical detection and treatment.

The specifics of CpG islets methylation of some genes of peripheral blood T-lymphocytes in breast cancer patients before and after treatment

Introduction. The growth of primary breast tumor morbidity in the last ten years and increased number of patients with disseminated breast cancer in the Republic of Kazakhstan require the search for methods of early diagnosis of malignant tumors. Determination of breast cancer markers in epigenetic studies allows to use them as diagnostic signs of the presence of malignant tumor and as predictors of treatment effectiveness in patients with this pathology.Aim. To perform  a search for therapeutic and prognostic breast cancer markers.Materials and methods. The study included samples of biological material (peripheral blood) of 50 deemed healthy individuals and 103 patients with locally advanced and disseminated breast cancer receiving special therapy. The following methods were used: blood collection, DNA extraction, creation of DNA methylation profiles, sequencing, statistical data analysis.Results. The results of search for epigenetic mutations in peripheral blood of patients with breast cancer showed their role as specific diagnostic, therapeutic and prognostic markers with specificity 0.91 % and sensitivity 0.94 %. The hypothesis on therapeutic  significance of identified earlier diagnostic markers in patients  with breast cancer, namely hypermethylation of CpG islands associated with genes JAM3, C17orf64,  MSC, C7orf51  and CpG island associated with intragene part of chromosome 5 (chr5: 77,208,034–77,329,434) was tested and confirmed.Conclusion. A correlation between DNA methylation characteristics and disease progression during treatment was shown. The study results can be used in clinical practice: epigenetic markers, such as methylation in the CpG islets associated with the JAM3, C17orf64, MSC, C7orf51 genes, and in the CpG islet associated with the intragenic site of chromosome 5 (chr5: 77,208,034–77,329,434) can be used as prognostic markers and therapeutic predictors of breast cancer.

Laboratory Diagnostic Tests in Patients with Sepsis

Background: Sepsis is a syndrome involving physiological, pathological, and biochemical abnormalities caused by infection and leads to the dysfunction of various organs, including the liver and kidneys. It can lead to high mortality rates. Objectives: This study aimed to evaluate the hepatic, renal, and coagulation diagnostic markers in patients with sepsis. Methods: This cross-sectional analytical study was performed on patients with sepsis admitted to Abadan and Khorramshahr educational hospitals during March 21 2019-March 19, 2020. The hospital information system (HIS) collected the information of 305 patients with sepsis, including hepatic, coagulation, and renal diagnostic factors, as well as age and gender. Results: It was observed that the mean of blood sugar (BS) (145.82 ± 105.10 mg/dL), BUN (29.64 ± 27.41 mg/dL), and creatinine (1.69 ± 1.9 mg/dL) in sepsis patients was higher than normal. In addition, the mean of diagnostic markers of the liver, including ALT (47.27 ± 76.63 U/L), AST (74.38 ± 163.96 U/L), LDH (684.69 ± 383.96 U/L), total bilirubin (1.39 ± 1.02 mg/dL), and direct bilirubin (0.60 ± 0.65 mg/dL), was higher than normal. The mean of PT (16.73 ± 9.31 sec) and INR (1.72 ± 1.53) was also higher than the normal level. Conclusions: In hospitalized patients with sepsis, BS, renal diagnostic markers, hepatic diagnostic markers, and coagulation markers are higher than normal, indicating the destructive effect of sepsis on kidney and liver function.

Serum angiopoietin 1 level in patients with severe COVID-19: An observational study

Background: Exocytosis of the endothelial storage granules, Weibel-Palade bodies, upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion with the consequent release of P-selectin and Von Willebrand factor, as well as several chemokines, results in hypercoagulability. Angiopoietin-2 is a chemokine stored in Weibel-Palade bodies; it is a context-dependent competitive antagonist of angiopoietin-1. Disruption of the angiopoietin/Tie2 pathway contributes to vascular dyshomeostasis in sepsis. This study aimed to investigate serum levels of angiopoietin-1 in patients with severe coronavirus disease 2019 (COVID-19). Methods: A total of 85 participants were enrolled in the study and divided into two groups: the first group included 45 patients with severe COVID-19, and the second group included 40 healthy individuals of comparable age and sex to serve as the control group. ELISA was used to measure serum angiopoietin-1 levels. Results: Serum angiopoietin-1 levels were significantly lower in patients with severe COVID-19 than in control subjects (14.52 (5.56) ng/ml and 30.56 (17.56) ng/ml, respectively; p < 0.001). Moreover, at a cut-off value ≤21.05 ng/ml, serum angiopoietin-1 level had 97.8% sensitivity and 100% specificity in differentiating between severe COVID-19 patients and non-infected individuals (p-value <0.001). Conclusions: Serum angiopoietin-1 levels were lower in patients with severe COVID-19 than in control subjects, and it has potential to be used as a diagnostic marker for patients with severe COVID-19.

Deregulated Expression of IL-37 in Patients with Bladder Urothelial Cancer: The Diagnostic Potential of the IL-37e Isoform

Cellular and molecular immune components play a crucial role in the development and perpetuation of human malignancies, shaping anti-tumor responses. A novel immune regulator is interleukin-37 (IL-37), already shown to be involved in the inflammation associated with the pathophysiology of many human disorders, including cancer. The interplay between tumor and immune cells is of great importance, especially for highly immunogenic tumors such as bladder urothelial carcinoma (BLCA). This study aimed to investigate the potential of IL-37 and its receptor SIGIRR (single immunoglobulin IL-1-related receptor) to serve as prognostic and/or diagnostic markers in patients with BLCA. To this end, a series of bioinformatics tools processing -omics datasets and specifically designed qPCR assays on human BLCA tumors and cancer cell lines were utilized. Bioinformatics analysis revealed that IL-37 levels correlate with BLCA tumor development and are higher in patients with longer overall survival. Furthermore, mutations on SIGIRR are associated with enhanced infiltration of the tumor by regulatory T cells and dendritic cells. Based on the qPCR validation experiments, BLCA epithelial cells express the IL-37c and IL-37e isoforms, while the latter is the predominant variant detected in tumor biopsies, also associated with higher grade and the non-muscle-invasive type. This is the first time, to the best of our knowledge, that IL-37 and SIGIRR levels have been assessed in BLCA tumor lesions, and associations with pathological and survival parameters are described, while a transcript variant-specific signature is indicated to have a diagnostic potential. These data strongly indicate the need for further investigation of the involvement of this cytokine and interconnected molecules in the pathophysiology of the disease and its prospective as a therapeutic target and biomarker for BLCA.

Analysis of the Diagnostic Markers in Patients with Post-COVID-19 Disorders

Analysis of the Diagnostic Markers in Patients with Post-COVID-19 Disorders

Investigating the role of FADS family members in breast cancer based on bioinformatic analysis and experimental validation.

Breast cancer (BC) is the most common malignant tumor in women worldwide. Emerging evidence indicates the significance of fatty acid metabolism in BC. Fatty acid desaturase (FADS) is closely associated with cancer occurrence and development. Here, bioinformatic analysis and experimental validation were applied to investigate the potential functions of FADS in BC. Several public databases, including TCGA, GEO, HPA, Kaplan-Meier plotter, STRING, DAVID, cBioPortal, TIMER, TRRUST, and LinkedOmics were used to determine mRNA/protein expression levels, prognostic significance, functional enrichment, genetic alterations, association with tumor-infiltrating immune cells, and related transcription factors and kinases. BC tissues showed higher and lower mRNA expression of FADS2/6/8 and FADS3/4/5, respectively. FADS1/2/6 and FADS3/4/5 showed higher and lower protein expression levels, respectively, in BC tissues. Moreover, FADS1/7 up- and FADS3/8 down-regulation predicted poor overall and recurrence-free survival, while FADS2/5 up- and FADS4 down-regulation were associated with poor recurrence-free survival. Receiver operating characteristic curves revealed that FADS2/3/4/8 were indicative diagnostic markers. FADS family members showing differential expression levels were associated with various clinical subtypes, clinical stages, lymph node metastasis status, copy number variants, DNA methylation, and miRNA regulation in BC. The mRNA expression level of FADS1/2/3/4/5/7/8 was observed to be significantly negatively correlated with DNA methylation. FADS1/2 upregulation was significantly correlated with clinical stages. FADS1/4 expression was obviously lower in BC patients with higher lymph node metastasis than lower lymph node metastasis, while FADS7/8 expression was obviously higher in BC patients with higher lymph node metastasis than lower lymph node metastasis. FADS family members showed varying degrees of genetic alterations, and Gene Ontology and KEGG pathway enrichment analyses suggested their involvement in lipid metabolism. Their expression level was correlated with immune cell infiltration levels. FADS2 was chosen for further validation analyses. We found FADS2 to be significantly over-expressed in clinical BC tissue samples. The proliferation, migration, and invasion abilities of MDA-MB-231 and BT474 cells were significantly reduced after FADS2 knockdown. Furthermore, FADS2 may promote the occurrence and development of BC cells via regulating the epithelial-mesenchymal transition (EMT) pathway. Altogether, our results suggest that FADS1/2/3/4 can serve as potential therapeutic targets, prognostic indicators, and diagnostic markers in patients with BC.

DOP13 Plasma metabolite fingerprint could discriminate inflammatory bowel disease patients from healthy subjects

Abstract Background Inflammatory bowel diseases (IBD, Crohn’s disease [CD], ulcerative colitis [UC]) are chronic immune-mediated systemic diseases with unknown aetiology. In the past few years, experimental studies revealed associations of human serum and plasma metabolites’ with IBD with a possible discriminative power between IBD and healthy subjects. Our study focused on the utility of plasma metabolome profiling as a diagnostic marker in patients with different phenotypes. Methods IBD patients were enrolled in a double-centre prospective cohort study. Large number of healthy subjects were included to reduce methodological bias. Blood samples were obtained at baseline and stored at –20°C and plasma metabolites were measured by high performance liquid chromatography coupled with tandem-mass spectrometry (HPLC-MS/MS). Logistic regression, minimum redundancy maximal relevance (mRMR), principal component analysis (PCA), and linear discriminant analysis (LDA) were used to calculate discriminative power. Results Plasma metabolome profile of 26 IBD (13 UC and 12 CD) patients and 168 HC participants were analyzed, and 388 metabolites were measured. 33 and 58% of CD patients and 31 and 39% of UC patients had clinical and endoscopic activity based on clinical (mean pMayo: 2.8±3.4, CDAI: 56±62) and endoscopic (mean PanMayo: 7.4±13.3 and SES-CD: 7.3±8.2) indices. Low plasma level of cysteine (CV=-0.36; p<0.01), triglycerides (CV=-0.19; p<0.01) and hexosylceramide (HexCer(d18:1/23:0); CV=-0.18; p<0.01), while high level of arginine (CV=0.3; p<0.24), hexosylceramide (HexCer(d18:2/23:0); CV=0.2; p=0.02), glutamate (CV=0.19; p<0.01) and lactate (CV=0.16; p=0.01) were significantly associated with IBD. According to mRMR analysis, cysteine (p<0.001), triglyceride (p<0.01), and HexCer(d16:1/22:0); (p<0.001) ranked highest in terms of feature importance (discriminative power). Based on the 16 metabolites considered to be of the highest discriminative power, the healthy and the IBD groups were well separated (PC1=18.2%, PC2=14.7%; Figure 1.). Conclusion Based on our results, plasma metabolite levels may help to discriminate IBD and healthy subjects. Integrative analysis of different biological samples may potentially predict IBD and could promote achieving personalized medicine. Further sample collections and analysis within this study can reveal discriminative metabolite fingerprints among IBD subtypes and correlations with activity as well.