The Impact of Biomarkers in Pancreatic Ductal Adenocarcinoma on Diagnosis, Surveillance and Therapy

Pancreatic ductal adenocarcinoma (PDAC) is still difficult to treat due to insufficient methods for early diagnosis and prediction of therapy response. Furthermore, surveillance after curatively intended surgery lacks adequate methods for timely detection of recurrence. Therefore, several molecules have been analyzed as predictors of recurrence or early detection of PDAC. Enhanced understanding of molecular tumorigenesis and treatment response triggered the identification of novel biomarkers as predictors for response to conventional chemotherapy or targeted therapy. In conclusion, progress has been made especially in the prediction of therapy response with biomarkers. The use of molecules for early detection and recurrence of PDAC is still at an early stage, but there are promising approaches in noninvasive biomarkers, composite panels and scores that can already ameliorate the current clinical practice. The present review summarizes the current state of research on biomarkers for diagnosis and therapy of pancreatic cancer.

Urinary MicroRNA Expression Analysis of miR-1, miR-215, miR-335, Let-7ain Childhood Nephrotic Syndrome

Background Recently, urinary exosomal miRNAs are gaining increasing attention as their expression profiles are often associated with specific diseases and they exhibit great potential as noninvasive biomarkers for the diagnosis of various diseases. The present study was aimed to evaluate the expression status of selected miRNAs (miR-1, miR-215-5p, miR-335-5p and let-7a-5p) in urine samples from children with NS [steroid sensitive (SSNS)] and [steroid resistant (SRNS)] along with healthy control group.Methods MicroRNA isolation was carried out in urine samples collected from SSNS (100 nos), SRNS (100 nos), and healthy controls (50 nos) using MiRNeasy Mini Kit, followed by cDNA conversion for all the four selected miRNAs using Taqman advanced miRNA cDNA synthesis kit and their expression was quantified by Taqman Advanced miRNA assay kits using Real Time PCR Machine and Rotogen-Q in SSNS and SRNS patients and healthy control subjects.ResultsQuantification of all the four miRNAs (miR-1, mir-215, miR-335, let 7a) were found to be upregulated in both SSNS and SRNS as compared to control group. Further, the comparison of microRNAs within the case groups revealed significant downregulation of three microRNAs - miR-1, miR-215, miR- 335 and upregulation of let-7a in SRNS group as compared to SSNS. The t-test performed for all the four miRNAs was found to be statistically significant. ConclusionsThe aberrant expression of all the four microRNAs in both SSNS and SRNS as compared to healthy subjects may serve as novel biomarkers to distinguish between NS and healthy controls. The differential expression of microRNA let-7a is useful to discriminate SSNS and SRNS.

Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status

Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured via enzyme-linked immunosorbent assay. In patients with IgAN, higher u-sCD163 levels were associated with histological lesions of greater severity, as well as more proteinuria and poorer renal function. Additionally, u-sCD163 was correlated with infiltration of tubulointerstitial CD163+ macrophages. High u-sCD163 levels (>3.57 ng/mg Cr) were associated with a 2.66-fold greater risk for IgAN remission failure in adjusted analyses. Adding u-sCD163 levels to the model containing clinical data at biopsy and MEST-C score significantly improved the risk prediction of IgAN remission status (AUC 0.788). Together, our results suggest that u-sCD163 may be a useful noninvasive biomarker to evaluate disease severity and remission status of IgAN.

Advances regarding Neuroinflammation Biomarkers with Noninvasive Techniques in Epilepsy

A rapidly growing body of evidence supports that neuroinflammation plays a major role in epileptogenesis and disease progression. The capacity to identify pathological neuroinflammation in individuals with epilepsy is a crucial step on the timing of anti-inflammatory intervention and patient selection, which will be challenging aspects in future clinical studies. The discovery of noninvasive biomarkers that are accessible in the blood or molecular neuroimaging would facilitate clinical translation of experimental findings into humans. These innovative and noninvasive approaches have the advantage of monitoring the dynamic changes of neuroinflammation in epilepsy. Here, we will review the available evidence for the measurement of neuroinflammation in patients with epilepsy using noninvasive techniques and critically analyze the major scientific challenges of noninvasive methods. Finally, we propose the potential for use in clinical applications.

Evaluation of Serum miR-17-92 Cluster as Noninvasive Biomarkers for Bladder Cancer Diagnosis

Previous studies have shown that the miR-17-92 cluster is involved in the occurrence and development of bladder cancer. However, the role of serum miR-17-92 cluster in the diagnosis of bladder cancer has not been studied. In the present study, we evaluated the expression of miR-17-92 cluster members in bladder cancer tissues by analyzing 428 cases from TCGA database. Next, we collected the sera of 74 bladder cancer patients and 90 controls, and used qRT-PCR to detect the relative expression of the cluster. The results showed that the expression of the cluster members in the sera of patients were significantly higher than that of the controls, and they were positively correlated with the clinical stage and pathological grade of the patients. We evaluated their ability to diagnose bladder cancer using ROC, of which miR-92a-3p (AUC = 0.902), miR-17-5p (AUC = 0.845) and miR-20a-5p (AUC = 0.806) were the most prominent. Finally, we established a diagnostic model by logistic regression (AUC = 0.969). We further validated the results of the study using another dataset from the GEO database. Moreover, we evaluated the prognostic value of the cluster. The results revealed that miR-20a-5p was correlated with recurrence of bladder cancer. In summary, the present study validated the overexpression of serum miR-17-92 cluster in bladder cancer. The model composed of the three cluster members were confirmed to be a promising noninvasive biomarker for bladder cancer diagnosis.

Single cell profiling of Hofbauer cells and fetal brain microglia reveals shared programs and functions

SummaryMaternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many of which are mediated by in utero microglial programming. Microglia remain inaccessible at birth and throughout development, thus identification of noninvasive biomarkers that can reflect fetal brain microglial programming may permit screening and intervention during critical developmental windows. Here we used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells). Single-cell RNA sequencing of murine fetal brain and placental macrophages demonstrated shared transcriptional programs. Comparison with human datasets demonstrated that placental resident macrophage signatures are highly conserved between mice and humans. Single-cell RNA-seq identified sex differences in fetal microglial and Hofbauer cell programs, and robust differences between placenta-associated maternal macrophage/monocyte (PAMM) populations in the context of a male versus a female fetus. We propose that Hofbauer cells, which are easily accessible at birth, provide novel insights into fetal brain microglial programs, potentially facilitating the early identification of offspring most vulnerable to neurodevelopmental disorders.

Importance of miR-141-5p and miR-501-5P expression in patients with HBV infection

MicroRNAs (miRNAs) as small RNA and post-transcriptional modulators are shown to have regulatory effects for different cellular activities and pathways, such as metabolism, virus replication and also cell growth. In addition, miRNAs can regulate the replication of the hepatitis B virus (HBV). Therefore, the expression profile of miRNAs was evaluated in HBV-infected patient groups and healthy controls. The expression levels of the following microRNAs (as noninvasive biomarkers) were compared in two experimental (those with various stages of HBV infection) and control groups to evaluate their diagnosis ability: mir141-5p and mir501-5p. RNA extraction was performed for 45 serum samples. The miRCURY LNA™ Universal RT-miRNA-PCR system and miRNA PCR panels were used for measuring microRNA expression profiles. To normalize quantitative values, the endogenous reference by UniSp6 expression was used. Serum mir141-5p and mir501-5 were significant None in patient in different stages of HBV infection(p<0.001) than in controls(p<0.01). Receiver operating characteristic (ROC) curve analyses suggested that serum has mir141-5p and mir501-5p none significant diagnostic value for HBV infection. Results suggest that mir141-5p and mir501-5 can not be used as diagnostic biomarkers for monitoring of HBV infection and other biomarkers in this disease need to be investigated.