Presence of Filterable and Nonfilterable mRNA in the Plasma of Cancer Patients and Healthy Individuals

Ng, Enders K.W.; Tsui, Nancy B. Y.; Lam, Nicole Y.L.; Chiu, Rossa W.K.; Yu, Simon C.H.; Wong, Stephenie; Lo, Elena Siu Fong; Rainer, Timothy; Johnson, Philip J.; Lo, Y.M. Dennis

doi:10.1093/clinchem/48.8.1212

Cited by 238 publications

(94 citation statements)

References 15 publications

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“…We found in our present study that concentrations of cell-free mitochondrial plasma DNA and mRNA in patients with cancer were generally higher than in healthy control subjects, consistent with previous reports. (14,15) We also found that changes in mitochondrial DNA concentrations showed a pattern Plasma DNA concentration showed decreasing ( ) or increasing ( ) tendency during RT period; unclassified, changing without any tendency; peak +, DNA concentration increasing with a transient peak followed by decreasing; day, day of transient peak; peak %, ratio of DNA concentration at transient peak to that before treatment; local, local recurrence; CR, complete remission; dis met, distant metastasis; resi, residual tumor; A/D, alive with disease; A, alive without disease; D, dead of disease; d, dead of other cause. doi: 10.1111/j.1349-7006.2008.01021.x © 2008 Japanese Cancer Association independent of 100-bp and 400-bp genomic DNA concentrations during radiation therapy.…”

Section: Discussionmentioning

confidence: 99%

Quantification of circulating cell‐free DNA in the plasma of cancer patients during radiation therapy

Chen¹,

Omura-Minamisawa²,

Kang³

et al. 2009

Cancer Science

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Cell-free plasma DNA is elevated in cancer patients and decreases in response to effective treatments. Consequently, these nucleic acids have potential as new tumor markers. In our current study, we investigated whether the plasma DNA concentrations in patients with cancer are altered during the course of radiation therapy. To first determine the origin of cell-free plasma DNA, plasma samples from mice bearing transplanted human tumors were analyzed for human-specific and mouse-specific cell-free DNA. Human-specific DNA was detectable only in plasma from tumor-bearing mice. However, mouse-specific plasma DNA was significantly higher in tumorbearing mice than in normal mice, suggesting that cell-free plasma DNA originated from both tumor and normal cells. We measured the total cell-free plasma DNA levels by quantitative polymerase chain reaction in 15 cancer patients undergoing radiation therapy and compared these values with healthy control subjects. The cancer patients showed higher pretreatment plasma DNA concentrations than the healthy controls. Eleven of these patients showed a transient increase of up to eightfold in their cell-free plasma DNA concentrations during the first or second week of radiation therapy, followed by decreasing concentrations toward the end of treatment. In two other cancer patients, the cell-free plasma DNA concentrations only decreased over the course of the treatment. The total cell-free plasma DNA levels in cancer patients thus show dynamic changes associated with the progression of radiation therapy. Additional prospective studies will be required to elucidate the potential clinical utility and biological implications of dynamic changes in cell-free plasma DNA during radiation therapy. (Cancer Sci 2009; 100: 303-309) T he response of malignant tumors to radiation therapy varies, even if they show similar histopathological origins and clinical staging. An accurate assessment of the radiation sensitivity of individual tumors during the early phase of radiation therapy could provide valuable guidance for selecting the most appropriate treatment plan for individual patients, such as patientspecific modifications of the dose and field of radiation therapy, or additional or alternative therapeutic modalities earlier in the course of treatment. This in turn might contribute to better patient outcomes. However, conventional methods, including imaging diagnoses using computed tomography and magnetic resonance imaging or histopathological examination of biopsy samples, are limited in their ability to evaluate the radiation sensitivity of individual tumors during or immediately following radiation therapy. Hence, alternative assessment methods are required.Previous studies have shown that cell-free DNA is present in the bloodstream of cancer patients at higher concentrations than in healthy controls.(1-4) Although the cell origins and the mechanisms underlying cell-free DNA generation in cancer patients are not yet fully understood, it has been suggested that tumor cells might actively secr...

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Section: Discussionmentioning

confidence: 99%

Quantification of circulating cell‐free DNA in the plasma of cancer patients during radiation therapy

Chen¹,

Omura-Minamisawa²,

Kang³

et al. 2009

Cancer Science

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“…Specific primers and fluorescent probes for SARS-CoV and GAPDH mRNA detection (as described previously by us 13 ) were purchased from Applied Biosystems (table 2). The SARS-CoV primers and probe perfectly matched all available genomic sequences on GenBank.…”

Section: Q-rt-pcr Assaymentioning

confidence: 99%

Development of a quantitative assay for SARS coronavirus and correlation of GAPDH mRNA with SARS coronavirus in clinical specimens

Wong

2005

J Clin Pathol

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Aims: To develop a quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) for severe acute respiratory syndrome coronavirus (SARS-CoV) detection and explore the potential of using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA as an internal control to exclude false negative results. Methods: SARS-CoV and GAPDH mRNA were both measured in 26 specimens from 16 patients with SARS, 40 follow up specimens from the same batch of patients, and appropriate control subjects. The relation between SARS positivity and GAPDH mRNA concentration was investigated using the x 2 test. Increasing the sensitivity for SARS-CoV and GAPDH mRNA detection was investigated in follow up specimens in which SARS-CoV and GAPDH mRNA were not detected initially. Results: Varying amounts of SARS-CoV were found in the 26 SARS-CoV positive specimens and SARSCoV was not detected in the 40 follow up specimens and controls. In addition, concentrations of GAPDH mRNA were significantly different between the patients with SARS, follow up specimens, and healthy controls (Kruskal-Wallis test, p,0.05). Moreover, GAPDH mRNA concentrations were highly correlated with SARS-CoV positivity (x 2 = 5.43; p,0.05). Finally, SARS-CoV and GAPDH mRNA were both detected in three follow up urine specimens that were initially negative when the amount of cDNA used was increased from 5 ml to 10 and 15 ml. Conclusions: This Q-RT-PCR assay can be used to detect SARS-CoV. Moreover, GAPDH mRNA may be useful to rule out false negative results in SARS-CoV detection, and the current extraction method for urine may not be sensitive enough to detect low titres of SARS-CoV.

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“…Circulating RNA has been shown to be associated with subcellular particles of different sizes, which are removable by filtration and ultracentrifugation. 18 Approximately 70% of hPL and ␤-hCG mRNA can be removed from the maternal plasma by filtering the plasma sample through a 0.45-m filter. One possible source of these particle-associated placental RNA molecules would be the apoptotic shedding of microparticles from the placenta into the maternal circulation.…”

Section: Particalitymentioning

confidence: 99%

Placental RNA in Maternal Plasma

Tsui¹,

Lo²

2006

Annals of the New York Academy of Sciences

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The recent demonstration of the presence of placenta-derived fetal RNA in maternal plasma has opened up new opportunities for noninvasive prenatal investigation. Circulating fetal RNA analysis could in principle be applied to all pregnancies without the limitations by fetal gender or polymorphisms between the mother and fetus. The use of fetus- or disease-specific circulating RNA markers would greatly increase the number of markers that can be used for prenatal monitoring. With the recent advances in microarray technology, new placenta-derived plasma RNA markers could be rapidly identified. These newly identified placental transcripts were robustly detectable in maternal plasma and were pregnancy-specific. Remarkably, the relative concentrations of the placental mRNA in maternal plasma directly reflect the gene expression patterns in the placenta, an observation which suggests that placental gene expression level plays a predominant role in determining the placental mRNA concentrations in maternal plasma. Thus, fetal mRNA measurement in maternal plasma may be a useful tool for noninvasive prenatal placental gene expressing profiling.

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Presence of Filterable and Nonfilterable mRNA in the Plasma of Cancer Patients and Healthy Individuals

Cited by 238 publications

References 15 publications

Quantification of circulating cell‐free DNA in the plasma of cancer patients during radiation therapy

Quantification of circulating cell‐free DNA in the plasma of cancer patients during radiation therapy

Development of a quantitative assay for SARS coronavirus and correlation of GAPDH mRNA with SARS coronavirus in clinical specimens

Placental RNA in Maternal Plasma

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