Prognostic MicroRNA Panel for HCV-Associated HCC: Integrating Computational Biology and Clinical Validation

2021 ◽  
Author(s):  
Areeg M. Dabbish ◽  
Hana M. Abdelzaher ◽  
Moustafa Abohawya ◽  
Samir Shamma ◽  
Yosra H. Mahmoud ◽  
...  
Keyword(s):  
Bioinformatic Analysis ◽  
Early Prediction ◽  
Serum Concentrations ◽  
Healthy Individuals ◽  
Non Invasive ◽  
Candidate Mirnas ◽  
Differentially Expressed Mirnas ◽  
Cirrhotic Patients ◽  
Mirnas Expression ◽  
Chronic Hcv

Abstract BackgroundEarly detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this poorly diagnosed widely-spread disease. Dysregulation in microRNA (miRNAs) expression is associated with HCC progression. MethodsThe objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Candidate miRNAs were selected using bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE- miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424 and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV and 72 HCV-associated HCC patients using real time PCR (qPCR).ResultsThere was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 expressions were significantly altered in HCC compared to non-cirrhotic patients. While miR-199a and miR-183 showed differential expression in cirrhotic relative to non-cirrhotic patients. A panel of 5 miRNAs improved sensitivity and specificity of HCC detection to 100% and 95.12% relative to healthy controls. Distinguishing HCC from HCV-treated patients was achieved by 70.8% sensitivity and 61.9% specificity using the combined panel, compared to alpha-fetoprotein (51.4% sensitivity and 60.67% specificity).ConclusionMiR-142, miR-183, miR-199a, miR-224 and miR-424 novel panel could serve as non-invasive biomarker for HCC early prediction in chronic HCV patients.

scholarly journals Identifying Differentially Expressed MicroRNAs Between Cirrhotic and Non-Cirrhotic Hepatocellular Carcinoma and Exploring Their Functions Using Bioinformatic Analysis

2018 ◽  
Vol 48 (4) ◽  
pp. 1443-1456 ◽  
Author(s):  
Ying Mei ◽  
Yu You ◽  
Jin Xia ◽  
Jian-Ping Gong ◽  
Yun-Bing Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Online Tools ◽  
Tumor Stages ◽  
Differentially Expressed Mirnas ◽  
Cancer Genome Atlas ◽  
Cirrhotic Patients ◽  
Independent Risk Factors

Background/Aims: Few studies have been designed to directly investigate the exact mechanisms underlying the different phenotypes between cirrhotic and non-cirrhotic hepatocellular carcinoma (HCC). This study aimed to illuminate the incidence and developmental mechanisms for both types of HCC through differentially expressed microRNAs (miRNAs) using bioinformatic analysis. Methods: The miRNA-seq data and clinical data of patients (from The Cancer Genome Atlas (TCGA) database) were utilized to determine differentially expressed miRNAs between cirrhotic and non-cirrhotic HCC. Afterwards, the function of the selected miRNAs was predicted with online tools. Furthermore, the miRNA expression and clinical significance were validated by external datasets and our experiment. Results: The present study included 135 non-cirrhotic and 80 cirrhotic patients to find differentially expressed miRNAs. Among them, four miRNAs (mir-1296, mir-23c, mir-149, and mir-95) were finally selected for further validation and analysis. Correlation analysis found that two miRNAs are greatly associated with the non-cirrhotic HCC patients’ clinical traits, such as the T, M, and N tumor stages. However, only mir-23c was associated with the cirrhotic HCC patients’ tumor T and N stages. Furthermore, survival analysis revealed that increased mir-149 in non-cirrhotic HCC, patients’ age and the existence of vessels in the tumor in cirrhotic HCC were independent risk factors for the patients’ postoperative overall survival. Functional and interaction analyses also supported the notion that these miRNAs function through some pathways that influence the behavior of the HCC. These results are strongly supported by analysis of extra datasets and our experiment. Conclusions: The cirrhotic and non-cirrhotic HCC types involve differentially expressed miRNAs, which are correlated with distinctive pathological traits. To some extent, non-cirrhotic HCC seems more dependent on miRNA network regulation, but additional studies are needed to confirm this conclusion.

scholarly journals Identification of MiRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 646
Author(s):  
Luis Javier Martínez-González ◽  
Victor Sánchez-Conde ◽  
Jose María González-Cabezuelo ◽  
Alba Antunez-Rodríguez ◽  
Eduardo Andrés-León ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Expression Patterns ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Non Invasive ◽  
Relevant Role ◽  
Cancer Genome Atlas ◽  
Mirnas Expression ◽  
Genome Atlas

MiRNAs play a relevant role in PC (prostate cancer) by the regulation in the expression of several pathways’ AR (androgen receptor), cellular cycle, apoptosis, MET (mesenchymal epithelium transition), or metastasis. Here, we report the role of several miRNAs’ expression patterns, such as miR-miR-93-5p, miR-23c, miR-210-3p, miR-221-3p, miR-592, miR-141, miR-375, and miR-130b, with relevance in processes like cell proliferation and MET. Using Trizol® extraction protocol and TaqMan™ specific probes for amplification, we performed miRNAs’ analysis of 159 PC fresh tissues and 60 plasmas from peripheral blood samples. We had clinical data from all samples including PSA, Gleason, TNM, and D’Amico risk. Moreover, a bioinformatic analysis in TCGA (The Cancer Genome Atlas) was included to analyze the effect of the most relevant miRNAs according to aggressiveness in an extensive cohort (n = 531). We found that miR-210-3p, miR-23c, miR-592, and miR-93-5p are the most suitable biomarkers for PC aggressiveness and diagnosis, respectively. In fact, according with our results, miR93-5p seems the most promising non-invasive biomarker for PC. To sum up, miR-210-3p, miR-23c, miR-592, and miR93-5p miRNAs are suggested to be potential biomarkers for PC risk stratification that could be included in non-invasive strategies such as liquid biopsy in precision medicine for PC management.

scholarly journals Elevated plasma miR-133b and miR-221-3p as biomarkers for early Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qihua Chen ◽  
Na Deng ◽  
Ke Lu ◽  
Qiao Liao ◽  
Xiaoyan Long ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Elevated Plasma ◽  
Rt Pcr ◽  
Circulating Micrornas ◽  
Non Invasive ◽  
Differentially Expressed Mirnas ◽  
Mirnas Expression ◽  
Early Parkinson’S Disease

AbstractBlood circulating microRNAs (miRNAs) are proposed to be promising biomarkers for many neurodegenerative disorders, including Parkinson’s disease (PD). However, there is a lack of identified differentially expressed miRNAs in PD from different studies. The aim of this study was to evaluate miRNAs expression in PD. We measured plasma circulating miRNA expression in three independent sets with a total of 151 PD patients, 21 multiple system atrophy (MSA) patients and 138 healthy controls using high-throughput RT-PCR. We identified that elevated miR-133b and miR-221-3p discriminated early-stage PD from controls with 94.4% sensitivity and 91.1% specificity. Elevated miR-133b and miR-221-3p distinguished PD from controls with 84.8% sensitivity and 88.9% specificity. In addition, miR-4454 distinguished PD from MSA with 57.1% sensitivity and 82.6% specificity. Hence, elevated miR-133b and miR-221-3p potentially represent good biomarkers for early PD, and a combination of miR-133b, miR-221-3p and miR-4454 has the potential to serve as a non-invasive biomarker for PD diagnosis.

scholarly journals Increased Serum Levels of Activated Caspases in Murine and Human Biliary Atresia

2021 ◽  
Vol 10 (12) ◽  
pp. 2718
Author(s):  
Omid Madadi-Sanjani ◽  
Gunnar Bohlen ◽  
Fabian Wehrmann ◽  
Julia Andruszkow ◽  
Karim Khelif ◽  
...  
Keyword(s):  
Liver Injury ◽  
Biliary Atresia ◽  
Caspase 3 ◽  
Serum Levels ◽  
Healthy Individuals ◽  
Serological Detection ◽  
Caspase Activation ◽  
Hepatocyte Apoptosis ◽  
Non Invasive ◽  
Cholestatic Diseases

In biliary atresia (BA), apoptosis is part of the pathomechanism, which results in progressive liver fibrosis. There is increasing evidence suggesting that apoptotic liver injury can be non-invasively detected by measuring the caspase activity in the serum. The purpose of this study was to investigate whether serological detection of caspase activation mirrors apoptotic liver injury in the infective murine BA-model and represents a suitable biomarker for BA in humans. Analysis showed increased caspase-3 activity and apoptosis in the livers of cholestatic BALB/c mice, which correlated significantly with caspase activation in the serum. We then investigated caspase activation and apoptosis in liver tissues and sera from 26 BA patients, 23 age-matched healthy and 11 cholestatic newborns, due to other hepatopathies. Compared to healthy individuals, increased caspase activation in the liver samples of BA patients was present. Moreover, caspase-3 activity was significantly higher in sera from BA infants compared to patients with other cholestatic diseases (sensitivity 85%, specificity 91%). In conclusion, caspase activation and hepatocyte apoptosis play an important role in experimental and human BA. We demonstrated that serological detection of caspase activation represents a reliable non-invasive biomarker for monitoring disease activity in neonatal cholestatic liver diseases including BA.

Non invasive diagnosis of portal hypertension in cirrhotic patients

2008 ◽  
Vol 32 (6) ◽  
pp. 80-87 ◽  
Author(s):  
F. Vizzutti ◽  
U. Arena ◽  
L. Rega ◽  
M. Pinzani
Keyword(s):  
Portal Hypertension ◽  
Non Invasive ◽  
Cirrhotic Patients

C reactive protein contributes to the early prediction of 90-day mortality risk in acutely decompensated cirrhotic patients

2017 ◽  
Vol 66 (1) ◽  
pp. S126-S127
Author(s):  
A. Clemente ◽  
M. Romero ◽  
C. Martínez ◽  
A. Bueno ◽  
M. Antona ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Early Prediction ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Cirrhotic Patients

scholarly journals Ascitic pseudouridine discriminates between hepatocarcinoma-derived ascites and cirrhotic ascites

1996 ◽  
Vol 42 (11) ◽  
pp. 1843-1846 ◽  
Author(s):  
G Castaldo ◽  
M Intrieri ◽  
G Calcagno ◽  
L Cimino ◽  
G Budillon ◽  
...  
Keyword(s):  
Liver Biopsy ◽  
Roc Curve ◽  
Curve Analysis ◽  
Diagnostic Sensitivity ◽  
Serum Concentrations ◽  
Diagnostic Specificity ◽  
Roc Curve Analysis ◽  
Neoplastic Cells ◽  
Cutoff Value ◽  
Cirrhotic Patients

Abstract Various biochemical indexes discriminate neoplastic from nonneoplastic ascites. However, within the latter group, the distinction between cirrhotic ascites and ascites caused by hepatocarcinoma (HC) is usually based on liver biopsy or cytology. HC-derived ascites is included in the group of nonneoplastic ascites because it is not associated with peritoneal spreading of neoplastic cells. In 54 cases of cirrhotic ascites and 17 cases of HC ascites, all histologically diagnosed, ascitic pseudouridine concentrations discriminated cirrhotic from HC ascites. For example, using the cutoff value of 4.25 mumol/L (obtained by ROC curve analysis) resulted in a diagnostic sensitivity of 88.2% and a diagnostic specificity of 90.8%. Moreover, in cirrhosis, the ascitic concentrations of pseudouridine were lower than serum concentrations, and the two sets of values were correlated; in HC, however, ascitic pseudouridine concentrations were higher than serum concentrations, and the two were unrelated. These findings strongly suggest that in cirrhotic patients ascitic pseudouridine derives from serum by diffusion, whereas in HC patients the mechanism appears to be more complex.

Non-invasive response prediction in prophylactic carvedilol therapy for cirrhotic patients with esophageal varices

2019 ◽  
Vol 70 (3) ◽  
pp. 412-422 ◽  
Author(s):  
Hwi Young Kim ◽  
Young Ho So ◽  
Won Kim ◽  
Dong-Won Ahn ◽  
Yong Jin Jung ◽  
...  
Keyword(s):  
Esophageal Varices ◽  
Response Prediction ◽  
Non Invasive ◽  
Cirrhotic Patients

scholarly journals Introduction of a Portable and Non-invasive Technology for Hand and Foot Cooling: A Preclinical Feasibility Study

2021 ◽  
Author(s):  
Shirin Davarpanah Jazi ◽  
Johan Ralf ◽  
Mohammad FazelBakhsheshi
Keyword(s):  
Skin Temperature ◽  
Healthy Subjects ◽  
Cold Water ◽  
Healthy Individuals ◽  
Cooling Performance ◽  
Non Invasive ◽  
Reduced Dose ◽  
Before And After ◽  
Hands And Feet ◽  
Near Future

Abstract Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is caused by damage to neural structures in distal limbs. CIPN can lead to reduced dose or cessation of chemotherapy. Cooling the hands/feet has shown to be effective in reducing or preventing CIPN. However, when using ice bath or ice gloves/socks is no way to maintain the targeted temperature and prevent ice from melting. Also, patients have difficulty tolerating the freezing temperatures over long periods of chemotherapy. The aim of this study was to test the cooling performance of a recently developed non-invasive system that can ultimately replace current cooling methods.Methods: COOLPREVENT circulates cold water at tolerable temperatures into malleable gloves/socks. As well, COOLPREVENT does not require replacing of melted ice. We administered a cooling protocol via COOLPREVENT on three healthy subjects for 60 minutes. Immediately before and after cooling, skin temperature in the hands and feet were measured. Level of discomfort was also recorded during the cooling process.Results: Results showed that COOLPREVENT reduce skin temperature by 14.5±3.8°C and 10.7±1.7°C in the hands and feet, respectively within 60 minutes without significant discomfort.Conclusion: Although our study is limited by the small number of subjects and participation of healthy individuals, but we can conclude that COOLPREVENT can be a safe and appropriate method for hand and foot cooling. We hope that these preliminary findings can pave the way to designing clinical trials we plan to conduct in the near future.

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