Genomic profiling of circulating plasma RNA for the analysis of cancer.
BACKGROUND
The blood of cancer patients is known to contain fragments of RNA released from the tumor. The application of genomic profiling techniques to plasma RNA may allow the unbiased selection of cancer markers in the blood, but the informative value of genomic profiling of plasma RNA is currently unknown.


METHODS
We used cDNA microarray hybridization to perform genomic profiling of plasma RNA from colorectal cancer (CRC) patients and from healthy donors. From a list of 40 genes differentially upregulated in cancer patients, we randomly selected 4 genes for further characterization. These 4 markers were analyzed by quantitative reverse-transcription PCR in a wide set of samples including paired samples from the same CRC patients before and after surgical resection of the tumor.


RESULTS
Three of the selected markers - EPAS1, UBE2D3, and KIAA0101 - were confirmed by PCR to be significantly increased in cancer compared to healthy donors. Importantly, 2 of the markers, EPAS1 and UBE2D3, showed a significant decrease after surgery, returning to the levels of healthy donors. Finally, supervised class prediction using these 3 markers correctly (77%) assigned presurgery samples to the CRC group and assigned postsurgery samples from the same patients to the healthy group.


CONCLUSIONS
Our findings demonstrate the usefulness of gene expression profiling of circulating plasma RNA to find cancer markers of potential clinical value.
Collado
Manuel
M
Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Garcia
Vanesa
V
Garcia
Jose Miguel
JM
Alonso
Isabel
I
Lombardia
Luis
L
Diaz-Uriarte
Ramon
R
Fernández
Luis A López
LA
Zaballos
Angel
A
Bonilla
Félix
F
Serrano
Manuel
M
D051792:Basic Helix-Loop-Helix Proteins / Q000097:blood / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000601:surgery; D053487:DEAD-box RNA Helicases / Q000097:blood / Q000235:genetics; D004268:DNA-Binding Proteins; D005240:Feasibility Studies; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D009363:Neoplasm Proteins / Q000097:blood* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000097:blood / Q000235:genetics; D044763:Ubiquitin-Conjugating Enzymes / Q000097:blood / Q000235:genetics; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D053487:DEAD-box RNA Helicases; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D017413:Ribonucleoprotein, U2 Small Nuclear; D044763:Ubiquitin-Conjugating Enzymes; D000099162:Endothelial PAS Domain-Containing Protein 1; C425208:PCLAF protein, human; C097310:UBE2D3 protein, human; C467585:DDX46 protein, human