[-癌-] miRNAs in lung cancer
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miRNAs in lung cancer - Studying complex fingerprints in patient's blood cells
by microarray experiments
Andreas Keller, Petra Leidinger, Anne Borries1, Anke Wendschlag1, Frank
Wucherpfennig(1), Matthias Scheffler(1), Hanno Huwer(3), Hans-Peter Lenhof(4)
and Eckart Meese(2)
(1) febit biomed gmbh, Im Neuenheimer Feld 519, 69120 Heidelberg, Germany
(2) Department of Human Genetics, Medical School, Saarland University, Building
60, 66421 Homburg, Germany
(3) Department of Cardiothoracic Surgery, Voelklingen Heart Center, 66333
Voelklingen, Germany
(4) Center for Bioinformatics, Saarland University, Building E11, 66041
Saarbruecken, Germany
BMC Cancer 2009, 9:353doi:10.1186/1471-2407-9-353
Abstract Published: 6 October 2009
______________________________________________________________________________
Background
Deregulated miRNAs are found in cancer cells and recently in blood cells of
cancer patients. Due to their inherent stability miRNAs may offer themselves
for blood based tumor diagnosis. Here we addressed the question whether there
is a sufficient number of miRNAs deregulated in blood cells of cancer patients
to be able to distinguish between cancer patients and controls.
Methods
We synthesized 866 human miRNAs and miRNA star sequences as annotated in the
Sanger miRBase onto a microarray designed by febit biomed gmbh. Using the fully
automated Geniom Real Time Analyzer platform, we analyzed the miRNA expression
in 17 blood cell samples of patients with non-small cell lung carcinomas(NSCLC)
and in 19 blood samples of healthy controls.
Results
Using t-test, we detected 27 miRNAs significantly deregulated in blood cells
of lung cancer patients as compared to the controls. Some of these miRNAs
were validated using qRT-PCR. To estimate the value of each deregulated
miRNA, we grouped all miRNAs according to their diagnostic information that
was measured by Mutual Information. Using a subset of 24 miRNAs, a radial
basis function Support Vector Machine allowed for discriminating between
blood cellsamples of tumor patients and controls with an accuracy of 95.4%
[94.9%-95.9%], a specificity of 98.1% [97.3%-98.8%], and a sensitivity of
92.5% [91.8%-92.5%].
Conclusion
Our findings support the idea that neoplasia may lead to a deregulation of
miRNA expression in blood cells of cancer patients compared to blood cells of
healthy individuals. Furthermore, we provide evidence that miRNA patterns can
be used to detect human cancers from blood cells.
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