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1 Institute of Molecular Oncology and Departments of Chemical Pathology,
2 Diagnostic Radiology and Imaging,
3 Clinical Oncology, and
4 Accident and Emergency Medicine Academic Unit, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region.
5 Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong Special Administrative Region.
aAddress correspondence to this author at: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Room 38023, 1/F Clinical Sciences Bldg., 30-32 Ngan Shing St., Shatin, New Territories, Hong Kong SAR. Fax 852-2194-6171; e-mail loym{at}cuhk.edu.hk.
Background: As RNA is labile, we investigated whether circulating RNA in human plasma may be present in a particle-associated form.
Methods: Blood was collected from 27 healthy individuals and 16 hepatocellular carcinoma (HCC) patients. The plasma from each individual was processed by two means: filtration through filters with different pore sizes (from 5 µm to 0.22 µm) and ultracentrifugation. We assessed plasma RNA content by a real-time quantitative reverse transcription-PCR assay for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcripts and plasma DNA by a real-time quantitative PCR assay for the ß-globin gene.
Results: The plasma GAPDH mRNA concentrations in the healthy individuals were significantly different in every pair of these filter sizes (P <0.05 for each pair). Overall, the plasma GAPDH mRNA concentration was higher by a median of 15-fold (interquartile range, 10- to 24-fold) in the paired unfiltered sample than in the sample filtered through a 0.22 µm filter. In contrast, no significant difference was seen in ß-globin DNA concentrations among different pore-size-filtered plasma samples (P = 0.455). Similarly, a significant difference was observed for RNA, but not DNA, between unfiltered plasma and ultracentrifuged plasma (P <0.05). No significant difference in GAPDH mRNA concentrations was seen between the 0.22-µm-filtered plasma samples and the ultracentrifuged plasma samples (P >0.05). In HCC patients, filtration with a 0.22 µm filter produced a median 9.3-fold (interquartile range, 6.9- to 311-fold) reduction in GAPDH mRNA concentration in plasma. Plasma GAPDH mRNA concentrations in HCC patients were significantly higher than those in healthy individuals, both with or without filtration (P <0.0 5 for filtered plasma samples; P <0.005 for unfiltered plasma samples).
Conclusions: A substantial proportion of plasma mRNA species is particle-associated. In HCC patients, both circulating particle- and non-particle-associated plasma RNA are increased.
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S C C Wong, J K C Chan, K C Lee, E S F Lo, and D N C Tsang Development of a quantitative assay for SARS coronavirus and correlation of GAPDH mRNA with SARS coronavirus in clinical specimens J. Clin. Pathol., March 1, 2005; 58(3): 276 - 280. [Abstract] [Full Text] [PDF]
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K. Hamaoui, A. Butt, J. Powrie, and R. Swaminathan Concentration of Circulating Rhodopsin mRNA in Diabetic Retinopathy Clin. Chem., November 1, 2004; 50(11): 2152 - 2155. [Full Text] [PDF]
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A. Farina, C. W.M. Chan, R. W.K. Chiu, N. B.Y. Tsui, P. Carinci, M. Concu, I. Banzola, N. Rizzo, and Y.M. D. Lo Circulating Corticotropin-Releasing Hormone mRNA in Maternal Plasma: Relationship with Gestational Age and Severity of Preeclampsia Clin. Chem., October 1, 2004; 50(10): 1851 - 1854. [Full Text] [PDF]
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S C C Wong, E S F Lo, and M T Cheung An optimised protocol for the extraction of non-viral mRNA from human plasma frozen for three years J. Clin. Pathol., July 1, 2004; 57(7): 766 - 768. [Abstract] [Full Text] [PDF]
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E. K.O. Ng, A. El-Sheikhah, R. W.K. Chiu, K.C. A. Chan, M. Hogg, R. Bindra, T. N. Leung, T. K. Lau, K. H. Nicolaides, and Y.M. D. Lo Evaluation of Human Chorionic Gonadotropin {beta}-Subunit mRNA Concentrations in Maternal Serum in Aneuploid Pregnancies: A Feasibility Study Clin. Chem., June 1, 2004; 50(6): 1055 - 1057. [Full Text] [PDF]
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 N B Y Tsui, S S C Chim, R W K Chiu, T K Lau, E K O Ng, T N Leung, Y K Tong, K C A Chan, and Y M D Lo Systematic micro-array based identification of placental mRNA in maternal plasma: towards non-invasive prenatal gene expression profiling J. Med. Genet., June 1, 2004; 41(6): 461 - 467. [Full Text] [PDF]
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T. Wataganara, E. S. LeShane, A. Y. Chen, L. Borgatta, I. Peter, K. L. Johnson, and D. W. Bianchi Plasma {gamma}-Globin Gene Expression Suggests that Fetal Hematopoietic Cells Contribute to the Pool of Circulating Cell-Free Fetal Nucleic Acids during Pregnancy Clin. Chem., April 1, 2004; 50(4): 689 - 693. [Abstract] [Full Text] [PDF]
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T. El-Hefnawy, S. Raja, L. Kelly, W. L. Bigbee, J. M. Kirkwood, J. D. Luketich, and T. E. Godfrey Characterization of Amplifiable, Circulating RNA in Plasma and Its Potential as a Tool for Cancer Diagnostics Clin. Chem., March 1, 2004; 50(3): 564 - 573. [Abstract] [Full Text] [PDF]
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T. H. Rainer, N. Y.L. Lam, N. B.Y. Tsui, E. K.O. Ng, R. W.K. Chiu, G. M. Joynt, and Y.M. D. Lo Effects of Filtration on Glyceraldehyde-3-Phosphate Dehydrogenase mRNA in the Plasma of Trauma Patients and Healthy Individuals Clin. Chem., January 1, 2004; 50(1): 206 - 208. [Full Text] [PDF]
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N. Y.L. Lam, T. H. Rainer, R. W.K. Chiu, G. M. Joynt, and Y.M. D. Lo Plasma Mitochondrial DNA Concentrations after Trauma Clin. Chem., January 1, 2004; 50(1): 213 - 216. [Full Text] [PDF]
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C. B.M. Oudejans, A. T.J.J. Go, A. Visser, M. A.M. Mulders, B. A. Westerman, M. A. Blankenstein, and J. M.G. van Vugt Detection of Chromosome 21-encoded mRNA of Placental Origin in Maternal Plasma Clin. Chem., September 1, 2003; 49(9): 1445 - 1449. [Abstract] [Full Text] [PDF]
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J.-M. Costa, A. Benachi, M. Olivi, Y. Dumez, M. Vidaud, and E. Gautier Fetal Expressed Gene Analysis in Maternal Blood: A New Tool for Noninvasive Study of the Fetus Clin. Chem., June 1, 2003; 49(6): 981 - 983. [Full Text] [PDF]
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R. W.K. Chiu, L. Y.S. Chan, N. Y.L. Lam, N. B.Y. Tsui, E. K.O. Ng, T. H. Rainer, and Y.M. D. Lo Quantitative Analysis of Circulating Mitochondrial DNA in Plasma Clin. Chem., May 1, 2003; 49(5): 719 - 726. [Abstract] [Full Text] [PDF]
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E. K.O. Ng, T. N. Leung, N. B.Y. Tsui, T. K. Lau, N. S. Panesar, R. W.K. Chiu, and Y.M. D. Lo The Concentration of Circulating Corticotropin-releasing Hormone mRNA in Maternal Plasma Is Increased in Preeclampsia Clin. Chem., May 1, 2003; 49(5): 727 - 731. [Abstract] [Full Text] [PDF]
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E. K. O. Ng, N. B. Y. Tsui, T. K. Lau, T. N. Leung, R. W. K. Chiu, N. S. Panesar, L. C. W. Lit, K.-W. Chan, and Y. M. D. Lo From the Cover: mRNA of placental origin is readily detectable in maternal plasma PNAS, April 15, 2003; 100(8): 4748 - 4753. [Abstract] [Full Text] [PDF]
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N. B.Y. Tsui, E. K.O. Ng, and Y.M. D. Lo Stability of Endogenous and Added RNA in Blood Specimens, Serum, and Plasma Clin. Chem., October 1, 2002; 48(10): 1647 - 1653. [Abstract] [Full Text] [PDF]
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P. Anker and M. Stroun Progress in the Knowledge of Circulating Nucleic Acids: Plasma RNA Is Particle-Associated. Can It Become a General Detection Marker for a Cancer Blood Test? Clin. Chem., August 1, 2002; 48(8): 1210 - 1211. [Full Text] [PDF]
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