Aberrant Concentrations of Liver-Derived Plasma Albumin mRNA in Liver Pathologies

Chan, Rebecca Wing-Yan; Wong, John; Mok, Tony; Lo, Wyatt Y.W.; Lee, Vincent; To, Ka Fai; Lai, Paul B.S.; Rainer, Timothy Hudson; Lo, Y.M. Dennis; Chiu, Rossa W.K.

doi:10.1373/clinchem.2009.133355

Cited by 22 publications

(21 citation statements)

References 37 publications

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“…However, it is known that fetalderived cell-free RNA in maternal plasma circulates in mixture with cell-free RNA derived from the maternal hematopoietic system. Liver-specific transcripts, such as ALB, are also readily detectable in the plasma (41). We, therefore, identified and filtered the cell signature genes of individual placental cell types in our dataset by reanalyzing peripheral blood mononucleated cells (PBMCs) single-cell transcriptomic profiles and the tissue transcriptome data of leukocytes and liver from public databases (28,42) (Fig.…”

Section: Noninvasive Elucidation Of Placental Cellular Dynamics Durinmentioning

confidence: 99%

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Tsang

Vong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

259

267

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The human placenta is a dynamic and heterogeneous organ critical in the establishment of the fetomaternal interface and the maintenance of gestational well-being. It is also the major source of cell-free fetal nucleic acids in the maternal circulation. Placental dysfunction contributes to significant complications, such as preeclampsia, a potentially lethal hypertensive disorder during pregnancy. Previous studies have identified significant changes in the expression profiles of preeclamptic placentas using whole-tissue analysis. Moreover, studies have shown increased levels of targeted RNA transcripts, overall and placental contributions in maternal cell-free nucleic acids during pregnancy progression and gestational complications, but it remains infeasible to noninvasively delineate placental cellular dynamics and dysfunction at the cellular level using maternal cell-free nucleic acid analysis. In this study, we addressed this issue by first dissecting the cellular heterogeneity of the human placenta and defined individual cell-type-specific gene signatures by analyzing more than 24,000 nonmarker selected cells from full-term and early preeclamptic placentas using large-scale microfluidic single-cell transcriptomic technology. Our dataset identified diverse cellular subtypes in the human placenta and enabled reconstruction of the trophoblast differentiation trajectory. Through integrative analysis with maternal plasma cell-free RNA, we resolved the longitudinal cellular dynamics of hematopoietic and placental cells in pregnancy progression. Furthermore, we were able to noninvasively uncover the cellular dysfunction of extravillous trophoblasts in early preeclamptic placentas. Our work showed the potential of integrating transcriptomic information derived from single cells into the interpretation of cell-free plasma RNA, enabling the noninvasive elucidation of cellular dynamics in complex pathological conditions. single-cell transcriptomics | cell-free RNA | noninvasive prenatal testing | placenta | preeclampsia

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Section: Noninvasive Elucidation Of Placental Cellular Dynamics Durinmentioning

confidence: 99%

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Tsang

Vong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

259

267

View full text Add to dashboard Cite

show abstract

“…The liver being one of the largest organs of the body, suspect that RNA expressed by genes in the liver, such as ALB, should be detectable in the peripheral circulation because of cell death associated with typical cell turnover and/or with pathological damage [24]. Some researchers have suggested that ALB mRNA in blood originates from malignant or non malignant hepatocytes that have entered the peripheral circulation [27,28].…”

Section: Discussionmentioning

confidence: 99%

“…The amplification of ALB mRNA was monitored with an ABI Prism 7900 Sequence Detection System (Applied Biosystems) and Sequence Detection Software version 2.2 (Applied Biosystems). Absolute concentrations of ALB mRNA in plasma were expressed as the number of copies / ml [24].…”

Section: Quantitative Real Time-pcr Albumin Mrna (Alb Mrna)mentioning

confidence: 99%

Circulating Plasma Albumin mRNA as a Predictor of Liver Injury in Chronic Hepatitis C and Hepatocellular Carcinoma

Thabet¹,

Rady²,

Sabawi³

et al. 2011

Am. J. Biomed. Sci.

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Background: Analysis of circulating nucleic acids in plasma, such as cell free RNA offers an avenue for non invasive monitoring of a variety of physiological and pathological conditions. Aims: Because albumin is the most abundant protein in the body and is synthesized by the liver, the current study was designed to assess plasma albumin mRNA (ALB mRNA), as a non invasive diagnostic marker of liver injury in chronic HCV (CHC) and hepatocellular carcinoma (HCC).Patients and Methods: The study included 65 patients, 31 patients had CHC and 34 were of HCC as well as 25 healthy control subjects. Patients were subjected to clinical examination, abdominal ultrasonography, CT for HCC cases and laboratory investigations including liver function tests, AFP and plasma albumin mRNA by Real Time-PCR.Results: Patients with CHC and HCC have a significant increase in their plasma ALB mRNA than controls; the higher level was in HCC cases. At a cut-off >935 copies/ml, plasma ALB mRNA can discriminate liver diseased from healthy subjects, with a sensitivity of 81.5%, and specificity of 96%, while, elevated serum levels of ALT had a sensitivity of 32.3%, and specificity of 92%. However, at a cut off >20 ng/ml alpha feto protein (AFP) had a sensitivity of 55.9% and sensitivity of 91.2%.in diagnosis of HCC.Conclusion: ALB mRNA in plasma is liver specific; it is increased in liver disease suggesting liver pathology and may be more diagnostically sensitive than alpha-fetoprotein and Alanine aminotransaminase (ALT) serum levels. Thus, future studies should assess if the plasma concentration of ALB mRNA may be used as therapy monitoring.

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“…Albumin level is a component of the Child-Turcotte-Pugh scale, the Model of End-stage Liver Disease scale (specifically designed for the liver), and global scales such as the Sepsis-related Organ Failure scale and the Acute Physiology and Chronic Health Evaluation scale. Some authors (Chan, 2010) have detected albumin mRNA in the blood, indicating that cell death could occur in liver impairment, which would release this element to the blood. Unlike albumin, the albumin mRNA level increases at an early stage of liver impairment.…”

Section: Acute-phase Proteins and The Livermentioning

confidence: 99%

The Role of the Acute-Phase Proteins in the Development and Progression of Liver Diseases

Nahum¹,

Arturo²,

Juan³

et al. 2011

Acute Phase Proteins as Early Non-Specific Biomarkers of Human and Veterinary Diseases

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Aberrant Concentrations of Liver-Derived Plasma Albumin mRNA in Liver Pathologies

Abstract: BACKGROUND:We hypothesized that liver-derived mRNA, such as ALB (albumin) mRNA, would be released into human plasma with liver cell death.

Cited by 22 publications

References 37 publications

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Circulating Plasma Albumin mRNA as a Predictor of Liver Injury in Chronic Hepatitis C and Hepatocellular Carcinoma

The Role of the Acute-Phase Proteins in the Development and Progression of Liver Diseases

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