scholarly journals LncRNA expression profile, functional analysis and potential biomarkers in children with pancreaticobiliary maljunction

Author(s):  
Lian Zhao ◽  
San-li Shi ◽  
Wan-liang Guo

Abstract Background The present study was aimed to investigate the expression profile of long non-coding RNAs (lncRNAs) and its potential as biomarker for pancreaticobiliary maljunction (PBM). Methods The differential expression of lncRNA and messenger RNA (mRNA) from 15 pediatric patients with PBM and 15 control subjects were analyzed with microArray and validated with quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Gene Ontology enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were used to investigate the biological functions of these genes. The area under curve (AUC) of receiver operating characteristic (ROC) curve was used to predict the biomarker of lncRNA in PBM. Results There were 2915 mRNAs and 173 lncRNAs upregulated, 2121 mRNAs and 316 lncRNAs downregulated in PBM cases, respectively. The enriched GO associated with differentially expressed mRNA were extracellular matrix, extracellular region and kinetochore. The most enriched pathway of Protein digestion and absorption was associated with cancer and PI3K-Akt signaling. Cis- and Trans-target gene analysis indicated that mRNAs were predicted to be regulated by one lncRNA and one mRNA corresponded to several lncRNAs. The results showed that the expression trends of NR_110876, NR_132344, XR_946886 and XR_002956345 were consistent with the microarray results, and the difference was statistically significant NR_132344, XR_946886 and XR_002956345 (P < 0.05).The AUC of ROC curve was significant only for XR_946886 (0.837, P < 0.001). Conclusion The present study indicated that lncRNAs were involved the pathogenesis of common bile duct in PBM and XR_946886 would be biomarkers for PMB.

Author(s):  
Lian Zhao ◽  
San-li Shi ◽  
Wan-liang Guo

IntroductionPancreaticobiliary maljunction (PBM) leads to higher rates of complications, including cholangitis,pancreatitis, and malignancies. The present study was to investigat the expression profile of long non-coding RNAs (lncRNAs) and their potential role as biomarkers in children with pancreaticobiliary maljunction.Material and methodsThe differential expression of lncRNAs and mRNAs from 15 pediatric patients with pancreaticobiliary maljunction and 15 control subjects were analyzed using a commercial microarray and validated with qRT-PCR. The potential biological functions of differentially expressed genes were explored based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. The ability of potential lncRNA biomarkers to predict pancreaticobiliary maljunction was assessed based on the area under the receiver operating characteristic curve (AUC).ResultsThere were 2915 mRNAs and 173 lncRNAs upregulated, and 2121 mRNAs and 316 lncRNAs downregulated in pancreaticobiliary maljunction cases compared to controls. The enriched Gene Ontology categories associated with differentially expressed mRNAs were extracellular matrix, extracellular region, and kinetochore. The most enriched Kyoto Encyclopedia pathway was protein digestion and absorption, which has been associated with cancer and PI3K-Akt signaling. Analysis of cis- and trans-target genes predicted that a single lncRNA was able to regulate several mRNAs. The qRT-PCR results for NR_110876, NR_132344, XR_946886, and XR_002956345 were consistent with the microarray results, and the difference was statistically significant for NR_132344, XR_946886, and XR_002956345 (p < 0.05). AUC was significant only for XR_946886 (0.837, p < 0.001).ConclusionsOur results implicate lncRNAs in common bile duct pathogenesis in pancreaticobiliary maljunction, and they identify XR_946886 as a potential biomarker for the disease.


Author(s):  
G. W. Hacker ◽  
I. Zehbe ◽  
J. Hainfeld ◽  
A.-H. Graf ◽  
C. Hauser-Kronberger ◽  
...  

In situ hybridization (ISH) with biotin-labeled probes is increasingly used in histology, histopathology and molecular biology, to detect genetic nucleic acid sequences of interest, such as viruses, genetic alterations and peptide-/protein-encoding messenger RNA (mRNA). In situ polymerase chain reaction (PCR) (PCR in situ hybridization = PISH) and the new in situ self-sustained sequence replication-based amplification (3SR) method even allow the detection of single copies of DNA or RNA in cytological and histological material. However, there is a number of considerable problems with the in situ PCR methods available today: False positives due to mis-priming of DNA breakdown products contained in several types of cells causing non-specific incorporation of label in direct methods, and re-diffusion artefacts of amplicons into previously negative cells have been observed. To avoid these problems, super-sensitive ISH procedures can be used, and it is well known that the sensitivity and outcome of these methods partially depend on the detection system used.


1998 ◽  
Vol 80 (09) ◽  
pp. 372-375 ◽  
Author(s):  
Hidemi Yoshida ◽  
Tadaatsu Imaizumi ◽  
Koji Fujimoto ◽  
Hiroyuki Itaya ◽  
Makoto Hiramoto ◽  
...  

SummaryPlatelet-activating factor (PAF) acetylhydrolase is an enzyme that inactivates PAF. Deficiency of this enzyme is caused by a missense mutation in the gene. We previously found a higher prevalence of this mutation in patients with ischemic stroke. This fact suggests that the mutation might enhance the risk for stroke through its association with hypertension. We have addressed this hypothesis by analyzing the prevalence of the mutation in hypertension. We studied 138 patients with essential hypertension, 99 patients with brain hemorrhage, and 270 healthy controls. Genomic DNA was analyzed for the mutant allele by the polymerase-chain reaction. The prevalence of the mutation was 29.3% (27.4% heterozygotes and 1.9% homozygotes) in controls and 36.2% in hypertensives and the difference was not significant. The prevalence in patients with brain hemorrhage was significantly higher than the control: 32.6% heterozygotes and 6.1% homozygotes (p <0.05). PAF acetylhydrolase deficiency may be a genetic risk factor for vascular diseases.


2021 ◽  
pp. 1-10
Author(s):  
Lichao Xu ◽  
Shiqin Wang ◽  
Shengping Wang ◽  
Ying Wang ◽  
Wentao Li ◽  
...  

OBJECTIVES: To investigate whether the baseline apparent diffusion coefficient (ADC) can predict survival in the hepatocellular carcinoma (HCC) patients receiving chemoembolization. MATERIALS AND METHODS: Diffusion-weighted MR imaging of HCC patients is performed within 2 weeks before chemoembolization. The ADC of the largest index lesion is recorded. Responses are assessed by mRECIST after the start of the second course of chemoembolization. Receiver operating characteristic (ROC) curve analysis is performed to evaluate the diagnostic performance and determine optimal cut-off values. Cox regression and Kaplan–Meier survival analyses are used to explore the differences in overall survival (OS) between the responders and non-responders. RESULTS: The difference is statistically significant in the baseline ADC between the responders and non-responders (P <  0.001). ROC analyses indicate that the baseline ADC value is a good predictor of response to treatment with an area under the ROC curve (AUC) of 0.744 and the optimal cut-off value of 1.22×10–3 mm2/s. The Cox regression model shows that the baseline ADC is an independent predictor of OS, with a 57.2% reduction in risk. CONCLUSION: An optimal baseline ADC value is a functional imaging response biomarker that has higher discriminatory power to predict tumor response and prolonged survival following chemoembolization in HCC patients.


2021 ◽  
Vol 892 ◽  
pp. 173809
Author(s):  
Soudeh Ghafouri-Fard ◽  
Mohammad Taheri

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1132
Author(s):  
Emel Rothzerg ◽  
Xuan Dung Ho ◽  
Jiake Xu ◽  
David Wood ◽  
Aare Märtson ◽  
...  

The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (RUSC1-AS1, TBX2-AS1, PTOV1-AS1, UBE2D3-AS1, ERCC8-AS1, ZMIZ1-AS1, RNF144A-AS1, RDH10-AS1, TRG-AS1, GSN-AS1, HMGA2-AS1, ZNF528-AS1, OTUD6B-AS1, COX10-AS1 and SLC16A1-AS1) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma.


Author(s):  
Sreedevi Aithal ◽  
Venkatesh Aithal ◽  
Joseph Kei ◽  
Shane Anderson

Abstract Objectives The objective of this study was to describe wideband absorbance (WBA) findings in patients with cholesteatomas and retraction pockets (RPs). Design In this prospective study, tympanometry, audiometry, and wideband tympanometry (WBT) were performed on 27 ears with an RP (eight with epitympanic RP and 19 ears with mesotympanic RP), 39 ears with a cholesteatoma (23 ears with epitympanic and 16 ears with mesotympanic cholesteatomas [MCs]), and 49 healthy ears serving as controls. Results Mean WBA at ambient pressure (WBAamb) of both experimental groups was reduced significantly between 0.8 and 5 kHz relative to the control group. The difference between mean WBAamb and mean WBA at tympanometric peak pressure (WBATPP) was greater for the RP (0.12–0.16 between 0.5 and 1.5 kHz) than for the cholesteatoma group (0.03–0.11 between 0.6 and 3 kHz). Mean WBAamb of both epitympanic RP (ERP) and epitympanic cholesteatoma (EC) subgroups was significantly lower than that of the control group. Mean WBATPP of the ERP subgroup attained normal levels as per the control group, while mean WBATPP of EC subgroup was significantly lower than that of the control group at 0.8 to 1.5 kHz and 4 to 5 kHz. In contrast, both mesotympanic RP and MC subgroups demonstrated similar mean WBAamb and WBATPP values. No significant differences in WBAamb and WBATPP results between the RP and cholesteatomas groups were observed. Receiver operating characteristic (ROC) analyses indicated that the area under the ROC curve for distinguishing between the RP and cholesteatomas groups ranged from 0.44 to 0.60, indicating low accuracy in separating the two groups. Conclusion While it is not possible to distinguish between the RP and cholesteatomas groups based on the WBAamb and WBATPP results, it is potentially feasible to differentiate between the EC and ERP conditions. Further study using a large clinical sample is recommended to determine the sensitivity and specificity of the WBA test to identify the EC and ERP conditions.


2010 ◽  
Vol 13 (2) ◽  
pp. 134-139 ◽  
Author(s):  
Sandra A. Founds ◽  
Lauren A. Terhorst ◽  
Kirk P. Conrad ◽  
W. Allen Hogge ◽  
Arun Jeyabalan ◽  
...  

Background. The goal of this study was to further validate eight candidate genes identified in a microarray analysis of first trimester placentas in preeclampsia. Material and method. Surplus chorionic villus sampling (CVS) specimens of 4 women subsequently diagnosed with preeclampsia (PE) and 8 control women (C) without preeclampsia analyzed previously by microarray and 24 independent additional control samples (AS) were submitted for confirmatory studies by quantitative real-time polymerase chain reaction (qRT-PCR). Results. Downregulation was significant in FSTL3 in PE as compared to C and AS (p = .04). PAEP was downregulated, but the difference was only significant between C and AS (p = .002) rather than between PE and either of the control groups. Expression levels for CFH, EPAS1, IGFBP1, MMP12, and SEMA3C were not statistically different among groups, but trends were consistent with microarray results; there was no anti-correlation. S100A8 was not measurable in all samples, probably because different probes and primers were needed. Conclusions. This study corroborates reduced FSTL3 expression in the first trimester of preeclampsia. Nonsignificant trends in the other genes may require follow-up in studies powered for medium or medium/large effect sizes. qRT-PCR verification of the prior microarray of CVS may support the placental origins of preeclampsia hypothesis. Replication is needed for the candidate genes as potential biomarkers of susceptibility, early detection, and/or individualized care of maternal—infant preeclampsia.


Author(s):  
Nicholas Laughton

Wilms’ tumour is a pediatric tumour of the kidney that appears to be the result of abherrent embryonal renal development. The paired­box (PAX) gene family has previously been implicated in Wilm’s tumorogenesis. In this study, Nickel­Agarose Chromatin Enrichment (NACE) was used to identify genes whose expression is regulated by the ranscription cofactor Pax2. Of the genes identified by NACE, the extracellular signal metabolite WNT5A was chosen fro further study. The expression of WNT5A was measured in a set of tumour samples using quantitative real time polymerase chain reaction (qRT­PCR) and compared to a human fetal kidney control. Of the 38 samples tested, 76% showed significantly lower levelsof cytosolic messenger RNA (mRNA). This data, in conjunction with published data on Pax2 expression, suggests Pax2 inhibits the expression of WNT5A. When compared with histological reports for the tumours we examined, the expression data implies that WNT5A may have a role in regulation of tubule growth in the developing kidney


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