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Quantification of cytokeratin 5 mRNA expression in the circulation of healthy human subjects and after lung transplantation.

Nickerson DW, Presson AP, Weigt SS, Gregson AL, Belperio JA, Gomperts BN - PLoS ONE (2009)

Bottom Line: Circulating epithelial progenitor cells are important for repair of the airway epithelium in a mouse model of tracheal transplantation.All normal human subjects examined expressed cytokeratin 5 in their buffy coat in amounts that were not significantly influenced by age or gender.There was a profound, statistically significant decrease in cytokeratin 5 mRNA expression levels in lung transplant patients compared to healthy human subjects (p = 3.1x10(-13)) and to heart transplant recipients.

View Article: PubMed Central - PubMed

Affiliation: Mattel Children's Hospital at UCLA, Division of Hematology Oncology, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.

ABSTRACT

Background: Circulating epithelial progenitor cells are important for repair of the airway epithelium in a mouse model of tracheal transplantation. We therefore hypothesized that circulating epithelial progenitor cells would also be present in normal human subjects and could be important for repair of the airway after lung injury. As lung transplantation is associated with lung injury, which is severe early on and exacerbated during episodes of infection and rejection, we hypothesized that circulating epithelial progenitor cell levels could predict clinical outcome following lung transplantation.

Methodology/principal findings: Quantitative Real Time PCR was performed to determine peripheral blood mRNA levels of cytokeratin 5, a previously characterized marker of circulating epithelial progenitor cells. Cytokeratin 5 levels were evaluated in healthy human subjects, in lung transplant recipients immediately post-transplant and serially thereafter, and in heart transplant recipients. All normal human subjects examined expressed cytokeratin 5 in their buffy coat in amounts that were not significantly influenced by age or gender. There was a profound, statistically significant decrease in cytokeratin 5 mRNA expression levels in lung transplant patients compared to healthy human subjects (p = 3.1x10(-13)) and to heart transplant recipients. There was a moderate negative correlation between improved circulating cytokeratin 5 mRNA levels in lung transplant recipients with recovering lung function, as measured by improved FEV1 values (rho = -0.39).

Conclusions/significance: Levels of cytokeratin 5 mRNA, a proxy marker for circulating epithelial progenitor cells, inversely correlated with disease status in lung transplant recipients. It may therefore serve as a biomarker of the clinical outcome of lung transplant patients and potentially other patients with airway injury.

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Quantitative real-time PCR of CK5 expression in normal human subjects compared to lung transplant patients and heart transplant patients.A box plot demonstrates the differences between CK5 values in normal human subjects compared to lung transplant patients (p = 3.1×10−13). A further comparison is made between CK5 mRNA expression in the circulation of heart transplant patients (n = 6) and lung transplant patients (p = 0.004).
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pone-0005925-g003: Quantitative real-time PCR of CK5 expression in normal human subjects compared to lung transplant patients and heart transplant patients.A box plot demonstrates the differences between CK5 values in normal human subjects compared to lung transplant patients (p = 3.1×10−13). A further comparison is made between CK5 mRNA expression in the circulation of heart transplant patients (n = 6) and lung transplant patients (p = 0.004).

Mentions: We found a 75-fold decrease in CK5 mRNA expression in the cohort of lung transplant patient samples tested post-transplant in comparison to healthy control subjects with 95% CI (33.36, 204.9) and p-value of 3.1×10−13 by the Wilcoxon rank sum test. This result is highly significant even after correcting for the multiple testing per patient, which would conservatively suggest a 0.005 significance level (for approximately 10 tests). Figure 3 shows a boxplot comparison of ΔCt values between cases and controls.


Quantification of cytokeratin 5 mRNA expression in the circulation of healthy human subjects and after lung transplantation.

Nickerson DW, Presson AP, Weigt SS, Gregson AL, Belperio JA, Gomperts BN - PLoS ONE (2009)

Quantitative real-time PCR of CK5 expression in normal human subjects compared to lung transplant patients and heart transplant patients.A box plot demonstrates the differences between CK5 values in normal human subjects compared to lung transplant patients (p = 3.1×10−13). A further comparison is made between CK5 mRNA expression in the circulation of heart transplant patients (n = 6) and lung transplant patients (p = 0.004).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2691992&req=5

pone-0005925-g003: Quantitative real-time PCR of CK5 expression in normal human subjects compared to lung transplant patients and heart transplant patients.A box plot demonstrates the differences between CK5 values in normal human subjects compared to lung transplant patients (p = 3.1×10−13). A further comparison is made between CK5 mRNA expression in the circulation of heart transplant patients (n = 6) and lung transplant patients (p = 0.004).
Mentions: We found a 75-fold decrease in CK5 mRNA expression in the cohort of lung transplant patient samples tested post-transplant in comparison to healthy control subjects with 95% CI (33.36, 204.9) and p-value of 3.1×10−13 by the Wilcoxon rank sum test. This result is highly significant even after correcting for the multiple testing per patient, which would conservatively suggest a 0.005 significance level (for approximately 10 tests). Figure 3 shows a boxplot comparison of ΔCt values between cases and controls.

Bottom Line: Circulating epithelial progenitor cells are important for repair of the airway epithelium in a mouse model of tracheal transplantation.All normal human subjects examined expressed cytokeratin 5 in their buffy coat in amounts that were not significantly influenced by age or gender.There was a profound, statistically significant decrease in cytokeratin 5 mRNA expression levels in lung transplant patients compared to healthy human subjects (p = 3.1x10(-13)) and to heart transplant recipients.

View Article: PubMed Central - PubMed

Affiliation: Mattel Children's Hospital at UCLA, Division of Hematology Oncology, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.

ABSTRACT

Background: Circulating epithelial progenitor cells are important for repair of the airway epithelium in a mouse model of tracheal transplantation. We therefore hypothesized that circulating epithelial progenitor cells would also be present in normal human subjects and could be important for repair of the airway after lung injury. As lung transplantation is associated with lung injury, which is severe early on and exacerbated during episodes of infection and rejection, we hypothesized that circulating epithelial progenitor cell levels could predict clinical outcome following lung transplantation.

Methodology/principal findings: Quantitative Real Time PCR was performed to determine peripheral blood mRNA levels of cytokeratin 5, a previously characterized marker of circulating epithelial progenitor cells. Cytokeratin 5 levels were evaluated in healthy human subjects, in lung transplant recipients immediately post-transplant and serially thereafter, and in heart transplant recipients. All normal human subjects examined expressed cytokeratin 5 in their buffy coat in amounts that were not significantly influenced by age or gender. There was a profound, statistically significant decrease in cytokeratin 5 mRNA expression levels in lung transplant patients compared to healthy human subjects (p = 3.1x10(-13)) and to heart transplant recipients. There was a moderate negative correlation between improved circulating cytokeratin 5 mRNA levels in lung transplant recipients with recovering lung function, as measured by improved FEV1 values (rho = -0.39).

Conclusions/significance: Levels of cytokeratin 5 mRNA, a proxy marker for circulating epithelial progenitor cells, inversely correlated with disease status in lung transplant recipients. It may therefore serve as a biomarker of the clinical outcome of lung transplant patients and potentially other patients with airway injury.

Show MeSH
Related in: MedlinePlus