Marker For Diagnosis Of Disease Research Articles

Epigenetic Drug Interventions in Breast Cancer: A Narrative Review of Current Research and Future Directions

Breast cancer is a life-threatening disease known for its extensive molecular heterogeneity. The study of the breast cancer epigenome has revealed potential avenues for improving breast cancer treatment risk stratification, early detection, and treatment. With renewed interest in epigenetic-modifying pharmaceutical agents, namely DNA methyltransferase inhibitors (DNMTi), histone deacetylase inhibitors (HDACi), bromodomain and extra-terminal inhibitors (BETi), and enhancer of zeste homolog 2 inhibitors (EZH2i), there have been extensive preclinical and clinical studies to evaluate the safety and efficacy of these agents as potential treatments for breast cancer. In this review, we summarise and present the preclinical and clinical evidence for epigenetic drugs in treating breast cancer. We review the challenges associated with the translation of these findings into improved patient outcomes, namely the optimisation of dosage and treatment regimens, and the emergence of resistance. These challenges have been widely recognised in the field and are of utmost importance for the successful implementation of personalised medicine. While there is strong evidence that epigenetic alterations, consisting of changes in DNA methylation, histone modifications, and non-coding RNAs, play a crucial role in breast cancer initiation and development, additional research is warranted to elucidate the safety profile of long-term interventions involving epigenetic drugs and to validate the role of epigenetic markers in disease diagnosis, prognosis, and personalised treatment.

Differentially Expressed Blood ARLNC1 in Combination with PCA3/PSA have Reassuring Clinical Applications in the Early Diagnosis of Prostate Cancer in Iranians: A pilot study.

Prostate cancer (PCA) is the second most common malignancy in Western countries. Long non-coding RNAs are new markers in disease diagnosis. Our aim of this study was to investigate liquid biopsy biomarkers with high specificity and sensitivity for early diagnosis of PCA patients in Iran. Blood specimens were collected from 29 PCA, 32 benign prostate hyperplasia (BPH), and 29 control (CTRL) individuals. Real-time PCR analyzed expression amounts of PSA, ARLNC1, UCA1, and PCA3. The ROC curve (receiver operating characteristic curve) analysis evaluated the diagnostic power of the examined molecules for PCA. There was a significant upregulation of PCA3 in PCA and BPH groups compared to the controls (p values for PCA3=< 0.001 and BPH vs. CTRL = 0.0015) while there was no significant difference between PCA and BPH individuals. A significant upregulation of ARLNC1 was seen in BPH group compared to the controls (p value=0.0042). Also, PCA3 expression level showed a significant relationship with prostate volume. There was no significant difference in UCA1 and PSA expression levels among the three groups (>0.05). The PCA3/PSA ratio was significantly increased in PCA and BPH individuals vs. the CTRL group with high sensitivity and specificity. The gene expression of PCA3 and ARLNC1 in the BPH group showed a significant relationship with age. Our findings showed that in the diagnosis of prostate cancer, measuring the expression of PCA3, PSA, and ARLNC1 genes is necessary to determine the health, benign, or cancerous status of patients' prostate. Also, selecting the PCA3/PSA ratio provides a new approach for diagnosing this cancer if confirmed in a larger clinical sample size and functional studies.

Analysis of expression level of several cytokines and growth factors in cerespinal fluids extracted from spina bifida, transverse myelitis, and paralysis

Recent studies have indicated that there is an association between expression levels of cytokines and growth factors with different pathologies, including neuron damage disease. In this study, we used Luminex assay to analyse expression levels of several cytokines and growth factors in cerebral spinal fluids (CSF) of patients with neuron inflammation or damage including spina bida (SB), transverse myelitis (TM), and paralysis. Results showed that we had detected the expression of 22 factors, including ten inflammatory cytokines, six anti-inflammatory cytokines, and six growth factors, in the CSF isolated from patients. A group of factors expressed higher compared to others, including inflammatory cytokines (GM-CSF, IL-6, and TNF-α); anti-inflammatory cytokines (APRIL and IL-33R); and growth factors (GDF-15 và G-CSF). A group of factors that expressed lower compared to other factors includes inflammatory cytokines (IL-1β và IFN-γ), anti-inflammatory cytokines (IL-10 and BAFF), and growth factors (BMP-9, EGF, and NGF-β). Interestingly, two factors of IL-6 and GDF-15 expressed higher in CSF originated from paralysis patients compared to SB and TM patients, while IL-17A and TNF-α expressed higher in paralysis patients compared to TM, but not SB. Two factors of IL-21 and TNF-α expressed higher in CSF from SB compared to TM. Results from this study are novel and significant to contribute to the knowledge of cytokine and growth factor profiles in the CSF of SB, TM, and paralysis patients. However, it requires more investigation to develop these results into markers for disease diagnosis.

MicroRNA-642a-5p Targets DNA Damage-Inducible Transcript 4 to Suppress Hepatitis B Virus Hepatoma Carcinoma Cell

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors in clinical practice, with hepatitis B virus (HBV) being the most common risk factor for HCC. MicroRNAs (miRNAs) have emerged as a new marker for disease diagnosis and molecularly targeted therapies; however, the mechanism of miR-642a-5p in HBV-associated HCC remains unclear. Objectives: The aim of this study was to investigate the expression of miR-642a-5p, which targets DNA damage-inducible transcript 4 (DDIT4), in HBV-associated HCC, and its effect on the proliferation, migration, and invasion of HBV-positive HCC cells. Methods: miR-642a-5p in the serum of patients with HBV-associated liver cancer (LC), as well as miR-642a-5p and DDIT4 mRNA in LC tissues and cells, and HBV DNA in HBV-positive cells were detected. The targeting of DDIT4 by miR-642a-5p and the progression of cells were also examined. All cell experiments were repeated five times. Results: The results indicated that levels of miR-642a-5p were decreased, while levels of DDIT4 were increased in the serum, tissues, and cells of HBV-positive HCC patients. Overexpression of miR-642a-5p inhibited the progression of HBV-positive HCC cells, suppressed HBV DNA replication, cell proliferation, and invasion, and promoted apoptosis in HepG2.2.15 cells. Conclusions: In addition, miR-642a-5p directly targeted DDIT4, and knockdown of DDIT4 reversed the effects of miR-642a-5p upregulation, promoting the progression of HBV-positive HCC cells. In conclusion, miR-642a-5p is expressed at low levels in HBV-associated HCC and inhibits HBV DNA replication and tumor progression in HBV-positive HCC by targeting DDIT4. This study provides a foundation for molecular targeted therapy in HBV-positive HCC.

Enzymes as indispensable markers in disease diagnosis.

Enzymes have been usedfor disease diagnosis for many decades; however, advancements in technology like ELISA and flow cytometry-based detection havesignificantlyincreased their use and have increased the sensitivity of detection. Technological advancements in recombinant enzyme production haveincreased enzymatic stability,and the use ofcolorimetric-based and florescence-based assays has led to their increased use as biomarkers for disease detection. Enzymes like acid phosphatase, cathepsin, lactate dehydrogenase, thymidine kinaseand creatine kinase are indispensable markers for diagnosing cancer, cardiovasculardiseasesand others. This minireview summarizes various enzymes used in disease diagnosis, their metabolic role, market valueand potential as disease markers across various metabolic and other disorders.

Exosomes in Action: Unraveling Their Role in Autoimmune Diseases and Exploring Potential Therapeutic Applications.

Exosomes are double phospholipid membrane vesicles that are synthesized and secreted by a variety of cells, including T cells, B cells, dendritic cells, immune cells, are extracellular vesicles. Recent studies have revealed that exosomes can play a significant role in under both physiological and pathological conditions. They have been implicated in regulation of inflammatory responses, immune response, angiogenesis, tissue repair, and antioxidant activities, particularly in modulating immunity in autoimmune diseases (AIDs). Moreover, variations in the expression of exosome-related substances, such as miRNA and proteins, may not only offer valuable perspectives for the early warning, and prognostic assessment of various AIDs, but may also serve as novel markers for disease diagnosis. This article examines the impact of exosomes on the development of AIDs and explores their potential for therapeutic application.

Basement membrane proteins in extracellular matrix characterize NF1 neurofibroma development and response to MEK inhibitor.

Neurofibromatosis Type 1 (NF1) is one of the most common tumor-predisposing genetic disorders. Neurofibromas are NF1-associated benign tumors. A hallmark feature of neurofibromas is an abundant collagen-rich extracellular matrix (ECM) that constitutes >50% of the tumor dry weight. However, little is known about the mechanism underlying ECM deposition during neurofibroma development and treatment response. We performed a systematic investigation of ECM enrichment during plexiform neurofibroma (pNF) development, and identified basement membrane (BM) proteins, rather than major collagen isoforms, as the most upregulated ECM component. Following MEK inhibitor treatment, the ECM profile displayed an overall down-regulation signature, suggesting ECM reduction as a therapeutic benefit of MEK inhibition. Through these proteomic studies, TGF-β1 signaling was identified as playing a role in ECM dynamics. Indeed, TGF-β1 overexpression promoted pNF progression in vivo. Furthermore, by integrating single-cell RNA-sequencing, we found that immune cells including macrophages and T cells produce TGF-β1 to induce Schwann cells to produce and deposit BM proteins for ECM remodeling. Following Nf1 loss, neoplastic Schwann cells further increased BM protein deposition in response to TGF-β1. Our data delineate the regulation governing ECM dynamics in pNF and suggest that BM proteins could serve as markers for disease diagnosis and treatment response.

Mir-98-5p regulates gluconeogenesis and lipogenesis by targeting PPP1R15B in hepatocytes

Several reports suggest that circulatory miRNAs are deregulated in diverse diseases and used as markers for disease diagnosis and prognosis. Here we show that miR-98-5p, that is down-regulated in the circulation during diabetes, regulates hepatic gluconeogenesis and lipogenesis by targeting PPP1R15B. miR-98-5p overexpression significantly decreased the transcript and protein levels of PPP1R15B in hepatic HepG2 cells and increased p-eIF2α expression and these were prevented in the presence of its inhibitor. Two major hepatic hallmarks during diabetes i.e. hepatic lipid accumulation and glucose output were explored towards physiological relevance. As compared to scramble, overexpression of miR-98-5p decreased the transcript levels of both gluconeogenic and lipogenic genes together with a significant reduction in hepatic glucose production and fat accumulation in HepG2 cells. Using PASTAA to detect common transcription factors regulating these altered genes, CREB emerged as the most significantly enriched transcription factor. While miR-98-5p overexpression did not change the transcript levels of CREB, there was a significant change in its protein levels. While similar effects on gluconeogenic and lipogenic gene expression were detected using the PPP1R15B siRNA, the opposite was observed in the presence of miR-98-5p inhibitor alone. All these suggest that by targeting PPP1R15B, miR-98-5p regulates hepatic steatosis and glucose output; deregulation of which are characteristic hepatic features during diabetes. Therapeutic intervention of the miR-98/PPP1R15B axis might offer a potential strategy to target aberrant hepatic metabolism during diabetes.Graphical

The Function of BDNF and Its Receptor in the Male Genitourinary System and Its Potential Clinical Application

Background: Brain-derived neurotrophic factor (BDNF), as a member of the nerve growth factor family, has been mentioned more and more frequently in recent literature reports. Among them, content about the male genitourinary system is also increasing. Objective and Rationale: BDNF plays an important role in the male genitourinary system. At the same time, the literature in this field is constantly increasing. Therefore, we systematically summarized the literature in order to more intuitively show the function of BDNF and its receptor in the male genitourinary system and its potential clinical application. Search Methods: An electronic search of, e.g., PubMed, scholar.google and Scopus, for articles relating to BDNF and its receptor in the male genitourinary system. Outcomes: In the male genitourinary system, BDNF and its receptors TrkB and p75 participate in a series of normal physiological activities, such as the maturation and morphogenesis of testes and epididymis and maintenance of isolated sperm motility. Similarly, an imbalance of the circulating concentration of BDNF also mediates the pathophysiological process of many diseases, such as prostate cancer, benign prostatic hyperplasia, male infertility, diabetes erectile dysfunction, penile sclerosis, and bladder fibrosis. As a consequence, we conclude that BDNF and its receptor are key regulatory proteins in the male genitourinary system, which can be used as potential therapeutic targets and markers for disease diagnosis.

Genomic profiling in low grade serous ovarian cancer: Identification of novel markers for disease diagnosis and therapy

ObjectivesLow grade serous ovarian cancer (LGSOC) differs from high grade serous in terms of pathogenesis, molecular, genetic, and clinical features. Molecular studies have been hampered by small sample sizes, heterogenous histology, and lack of comprehensive testing. We sought to molecularly profile LGSOC in a homogenously tested, histologically confirmed cohort. MethodsUsing hot-spot and whole exome next generation sequencing (NGS), fusion gene analysis interrogating RNA, fragment analysis, in situ hybridization and/or immunohistochemistry, 179 specimens were evaluated by Caris Life Sciences (Phoenix, AZ). A second independent histologic review confirmed histology in 153 specimens. ResultsMost frequently mutated genes (5% or greater) were members of the mitogen-activated protein kinase (MAPK) pathway: KRAS (23.7%, n = 36), NRAS (11.2%, n = 19), NF1 (7.9%, n = 5), and BRAF (6.6%, n = 10). Class III mutations were seen in 3 of 10 BRAF mutations while 7 were Class I V600E. Overall, estrogen and progesterone receptor expression was 80.2% (n = 130) and 27.8% (n = 45), respectively. Of those that were hormone negative, nearly 50% contained KRAS or NF1 mutations. None were NRAS mutated. Markers of response to immunotherapy were low to absent. ConclusionBRAF mutations were seen to be lower than those traditionally reported. With increased MAPK activation resulting in ligand independent activation of ERα, a role of combination therapy with hormonal and targeted therapy should be considered as 49.2% of hormone negative specimens were KRAS or NF1 mutated. Absence of immunotherapy biomarkers suggest limited benefit to immunotherapeutic agents.

Profiling the serum proteome during Schistosoma mansoni infection in the BALB/c mice: A focus on the altered lipid metabolism as a key modulator of host-parasite interactions.

Schistosomiasis represents a condition in which every aspect of the disease, starting from skin invasion of the cercariae to egg laying by adult worms, incites a tissue response from the vertebrate host. This response, whether acute or chronic, leads to the appearance of reporter molecules of tissue injury in bodily fluids that could be surveyed as markers for disease diagnosis, status and prognosis. In this scenario, the serum proteome associated with a schistosome infection remains poorly explored; particularly by the use of high-throughput mass spectrometric instrumentation. In this study, we aimed to comparatively examine the serum proteome of control versus infected BALB/c mice, spanning the interval between the onset of egg laying and the peak of the acute phase of infection. Compositional analysis of the sera, using one dimensional reversed-phase fractionation of tryptic peptides coupled to mass spectrometry, allowed identification of 453 constituents. Among these, over 30% (143 molecules) were differentially present comparing sera from infected and non-infected mice, as revealed by quantitative label-free shotgun approach. The majority of proteins exhibiting altered levels was categorised as belonging to immune response (acute phase-related proteins) followed by those linked to lipid transport and metabolism. Inspection of the lipid profile from control and infected individuals demonstrated more pronounced and significant alterations in triglycerides, VLDL and HDL fractions (p<0,001), attesting for a disturbance in circulating lipid molecules, and suggesting a key role in host-parasite interactions. Our findings provide a global view of the serum proteome in the context of experimental schistosomiasis during the acute phase of infection. It contributes by listing key molecules that could be monitored to inform on the associated inflammatory disease status. We hope it will shed light into uncovered aspects of the Schistosoma mansoni parasitism in the vertebrate host, particularly those related to modulation of the lipid metabolism mediating immune responses.

Immune Profiling of COVID-19 in Correlation with SARS and MERS.

Acute respiratory distress syndrome (ARDS) is a major complication of the respiratory illness coronavirus disease 2019, with a death rate reaching up to 40%. The main underlying cause of ARDS is a cytokine storm that results in a dysregulated immune response. This review discusses the role of cytokines and chemokines in SARS-CoV-2 and its predecessors SARS-CoV and MERS-CoV, with particular emphasis on the elevated levels of inflammatory mediators that are shown to be correlated with disease severity. For this purpose, we reviewed and analyzed clinical studies, research articles, and reviews published on PubMed, EMBASE, and Web of Science. This review illustrates the role of the innate and adaptive immune responses in SARS, MERS, and COVID-19 and identifies the general cytokine and chemokine profile in each of the three infections, focusing on the most prominent inflammatory mediators primarily responsible for the COVID-19 pathogenesis. The current treatment protocols or medications in clinical trials were reviewed while focusing on those targeting cytokines and chemokines. Altogether, the identified cytokines and chemokines profiles in SARS-CoV, MERS-CoV, and SARS-CoV-2 provide important information to better understand SARS-CoV-2 pathogenesis and highlight the importance of using prominent inflammatory mediators as markers for disease diagnosis and management. Our findings recommend that the use of immunosuppression cocktails provided to patients should be closely monitored and continuously assessed to maintain the desirable effects of cytokines and chemokines needed to fight the SARS, MERS, and COVID-19. The current gap in evidence is the lack of large clinical trials to determine the optimal and effective dosage and timing for a therapeutic regimen.

The role of YKL-40 in the pathogenesis of autoimmune diseases: a comprehensive review.

YKL-40, a chitinase-3-like protein 1 (CHI3L1) or human cartilage glycoprotein 39 (HC gp-39), is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells and vascular smooth muscle cells. Its biological function is not well elucidated, but it is speculated to have some connection with inflammatory reactions and autoimmune diseases. Although having important biological roles in autoimmunity, there were only attempts to elucidate relationships of YKL-40 with a single or couple of diseases in the literature. Therefore, in order to analyze the relationship between YKL-40 and the overall diseases, we reviewed 51 articles that discussed the association of YKL-40 with rheumatoid arthritis, psoriasis, systemic lupus erythematosus, Behçet disease and inflammatory bowel disease. Several studies showed that YKL-40 could be assumed as a marker for disease diagnosis, prognosis, disease activity and severity. It is also shown to be involved in response to disease treatment. However, other studies showed controversial results particularly in the case of Behçet disease activity. Therefore, further studies are needed to elucidate the exact role of YKL-40 in autoimmunity and to investigate its potential in therapeutics.

RNA-targeting Therapy: A Promising Approach to Reach Non-Druggable Targets

The term "non-druggable" refers to a protein that cannot be targeted pharmacologically; recently, significant efforts have been made to convert these proteins into targets that are reachable or "druggable." Pharmacologically targeting these difficult proteins has emerged as a major challenge in modern drug development, necessitating the innovation and development of new technologies. The idea of using RNA-targeting therapeutics as a platform to reach unreachable targets is very appealing. Antisense oligonucleotides, nucleic acid or aptamers, RNA interference therapeutics, microRNA, and synthetic RNA are examples of RNA-targeting therapeutics. Many of these agents were FDA-approved for the treatment of rare or genetic diseases, as well as molecular markers for disease diagnosis. As a promising type of therapeutic, many studies are being conducted in order for more and more of them to be approved and used in different disease treatments and to shift them from treating rare diseases only to being used as more specific targeting agents in the treatment of various common diseases. This article will look at some of the most recent technological and pharmaceutical advances that have contributed to the erosion of the concept of undruggability.

4D Reconstruction and Identification of Carotid Artery Stenosis Utilizing a Novel Pulsatile Ultrasound Phantom.

As a major application focus of vascular ultrasonography, the carotid artery has long been the subject of phantom design and procedure focus. It is therefore important to devise procedures that are minimally invasive and informative, initially using a physiologically accurate anthropomorphic phantom to validate the methodology. In this article, a novel phantom design protocol is presented that enables the efficient production of a pulsatile ultrasound phantom consisting of soft and vascular tissue mimics, as well as a blood surrogate fluid. These components when combined give the phantom high acoustic compatibility and lifelike mechanical properties. The phantom was developed using "at-home" purchasable components and 3D printing technology. The phantom was subsequently used to develop a 4D reconstruction algorithm of the pulsing vessel in MATLAB. In pattern with recent developments in medical imaging, the 4D reconstruction enables clinicians to view vessel wall motion in a 3D space without the need for manual intervention. The reconstruction algorithm also produces measured inner luminal areas and vessel wall thickness, providing further information relating to structural properties and stenosis, as well as elastic properties such as arterial stiffness, which could provide helpful markers for disease diagnosis. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Constructing a pulsatile ultrasound phantom model Support Protocol: Creating a vascular mimic mold Basic Protocol 2: Creating a 4D reconstruction from ultrasound frames.

Circular RNAs hsa-circ0000175 and hsa-circ0044235 in plasma are novel biomarkers for new-onset rheumatoid arthritis

Circular RNAs (circRNAs) are a class of non-coding RNAs that could serve as potential molecular markers for disease diagnosis. However, the role of circRNAs in plasma from new-onset rheumatoid arthritis (RA) has not been extensively investigated. In this study, the expression of hsa-circ0000175 and hsa-circ0044235 in plasma from RA patients, healthy controls (HCs), systemic lupus erythematosus (SLE) patients, osteoarthritis (OA), and undiagnosed arthritis (UA) patients were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Correlation analysis was used to assess the correlation of the two circRNAs and clinical variables of RA. The receiver operating characteristic (ROC) curves were created to evaluate the diagnostic value and multivariate analysis (logistic regression) was performed to analyse the risk factors. We confirmed that hsa-circ0000175 was significantly elevated in plasma from patients with new-onset RA compared with HC and patients with new-onset SLE, but significantly was reduced when compared with OA + UA patients. Hsa-circ0044235 was found to be significantly decreased in plasma from patients with new-onset RA compared with HC and OA + UA patients, but was significantly increased compared with SLE patients. The expression of plasma hsa-circ0000175 in new-onset RA patients was associated with platelet count (PLT), plateletcrit (PCT), and platelet large cell ratio (PLR), the expression of plasma hsa-circ0044235 new-onset RA patients was associated with swollen joint count (SJC), painful joint count (PJC), and disease activity score 28 (DAS28). ROC curve analysis suggested that the combination of hsa-circ0000175 and hsa-circ0044235 has some value in the diagnosis of new-onset RA from HC, patients with SLE and patients with OA + UA. The logistic regression analysis revealed that the expression of hsa-circ0000175 and hsa-circ0044235 in plasma were risk factors for RA. This study suggests that the combination of plasma hsa-circ0000175 and hsa-circ0044235 improves the diagnostic accuracy for new-onset RA. Moreover, the expression levels of plasma hsa-circ0000175 and hsa-circ0044235 were associated with disease activity and severity of RA.

New Clue: Prediction from Cell-Free DNA

The main challenge for a positive long-term outcome in lung transplantation is the lack of early detection for chronic lung allograft dysfunction (CLAD). With advancements in technology, an increasing number of studies demonstrate that cell-free DNA (cfDNA) in body fluids could be used as a marker for disease diagnosis, prognosis or monitoring response to treatment. A previous report from this journal found the joint assessment of cfDNA and CXCL10 from brochoalveolar lavage (BAL) could determine the subphenotypes of CLAD and predict lung transplant survival. This is an exciting attempt in monitoring the progress for lung transplant recipients. More studies and better understanding of cfDNA are needed to develop an accessible and reliable biomarker to monitor the progress of CLAD to improve the long-term survival for lung transplant recipients.

Abstract A56: Identification of circulating miRNA signatures in rectal cancer

Abstract Colorectal cancer is the third most common cancer and the second leading cause of cancer death in Europe. Therefore, the search for new biomarkers to enable facilitate early diagnosis, prognosis, and individualized treatment is particularly warranted. From a clinical point of view, malignancies in the colon and the rectum (RC) present two distinct entities that require different treatment strategies, so CRC might not be considered as a single enteropathogenic entity. MicroRNA (miRNAs) are small noncoding RNA molecules involved in the post-transcriptional and translational regulation of gene expression. The discovery that miRNAs may act either as oncogenes or tumor suppressors has initiated extensive research. It was recently discovered that extracellular miRNAs circulate in the bloodstream and that such circulating miRNAs are remarkably stable. This has raised the possibility that miRNAs might serve as novel markers for disease diagnosis and prognosis. In the present study, we aimed to identify circulating miRNAs enabling early diagnosis and prognosis of RC. MiRNA expression levels (from plasma and plasma exosomes) were characterized by next-generation sequencing (NGS) in 24 patients with RC collected at 2-time intervals. The first sampling was collected at the time of diagnosis and the second sampling was conducted around 1 year after the diagnosis. The expression levels of miR-122 and miR-142 were identified to be associated with overall survival in RC patients. Their functional characteristics were tested in vitro on rectal cancer cell lines HRA16 and SW1463. Increased levels of miRNAs were associated with decreased long-term survival of cells. Identified miRNAs are currently being verified on a larger population of RC patients. This has raised the question whether miRNA can serve as biomarkers for rectal cancer, but prior to its clinical applications, clinical trials are warranted. Acknowledgments: This work was supported by AZV 17-30920A, GA17-16857S, and GA UK 302119. Citation Format: Klara Cervena, Alena Opattova, Barbara Pardini, Alessio Naccarati, Pavel Vodicka, Veronika Vymetalkova. Identification of circulating miRNA signatures in rectal cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A56.

Discovery of Urinary Proteomic Signature for Differential Diagnosis of Acute Appendicitis.

Acute appendicitis is one of the most common acute abdomens, but the confident preoperative diagnosis is still a challenge. In order to profile noninvasive urinary biomarkers that could discriminate acute appendicitis from other acute abdomens, we carried out mass spectrometric experiments on urine samples from patients with different acute abdomens and evaluated diagnostic potential of urinary proteins with various machine-learning models. Firstly, outlier protein pools of acute appendicitis and controls were constructed using the discovery dataset (32 acute appendicitis and 41 control acute abdomens) against a reference set of 495 normal urine samples. Ten outlier proteins were then selected by feature selection algorithm and were applied in construction of machine-learning models using naïve Bayes, support vector machine, and random forest algorithms. The models were assessed in the discovery dataset by leave-one-out cross validation and were verified in the validation dataset (16 acute appendicitis and 45 control acute abdomens). Among the three models, random forest model achieved the best performance: the accuracy was 84.9% in the leave-one-out cross validation of discovery dataset and 83.6% (sensitivity: 81.2%, specificity: 84.4%) in the validation dataset. In conclusion, we developed a 10-protein diagnostic panel by the random forest model that was able to distinguish acute appendicitis from confusable acute abdomens with high specificity, which indicated the clinical application potential of noninvasive urinary markers in disease diagnosis.

Clinical Significance of AFP, HGF and Micro RNA-122 Levels in Patients with Liver Cirrhosis and Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and is advanced by severe viral hepatitis B or C (HBV or HCV). HCC is frequently diagnosed late requiring costly surgical resection or transplantation. Alpha fetoprotein (AFP) measurements, together with ultrasound are the most non-invasive methods for detection of HCC. Also, serum levels of hepatocyte growth factor (HGF) vary in liver diseases, reflecting hepatic damage and hepatocellular dysfunction. The discovery of miRNAs circulating in the peripheral blood has opened new directions of research to identify new non-invasive markers for diagnosis of diseases . Objectives: To assess the serum level of HGF and AFP in patients with liver cirrhosis with HCV infection and those of HCC .Also, to evaluate the expression levels of circulating plasma miRNA-122 in Egyptian patients. Methodology: Anti-HCV and HCV RNA were detected by an enzyme immunoassay and the viral RNA mini kit respectively among patients with cirrhosis and HCC. Also, serum AFP and HGF concentration was measured by sandwich ELISA for patients with HCC, patients with cirrhosis and normal controls. Correlation between HGF levels AFP and biochemical (transaminases, prothrombin activity, albumin, bilirubin), or virological (hepatitis C virus load) parameters was analyzed. . Expression level of miRNA-122 in plasma using RT-PCR were determined. Results: The serum AFP level was significantly elevated in cirrhotic and HCC patients in comparison to the control, with the highest level in the HCC group. On the other hand, the HGF level was significantly higher in HCC group than patients with cirrhosis. For HGF, the sensitivity and specificity were better than AFP (95% and 80% respectively). MiRNA-122 showed significant elevation in patients with cirrhosis groups and HCC group (P = 0.001) in comparison to the control group. Receiver operator characteristic (ROC) curve analysis for miRNA-122 yielded 73% sensitivity and 96 % specificity for the differentiation of HCC patients from non-HCC at a cutoff 0.165. Conclusion: HGF was better than AFP as noninvasive biomarkers for the detection of HCC in HCV cirrhotic patients. As its specificity was 96 %. MiRNA-122 can be used as novel non-invasive biomarker for monitoring HCV related disease progression.