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Accepted on ,

Technical Briefs

Genomic Profiling of Circulating Plasma RNA for the Analysis of Cancer

¹ Spanish National Cancer Research Centre (CNIO), Madrid, Spain
² Department of Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain
³ Department of Pharmacogenetics and Pharmacogenomics, Hospital Universitario Gregorio Marañón, Madrid, Spain
⁴ National Centre of Biotechnology (CNB-CSIC), Campus Universidad Auto'noma, Madrid, Spain

^* To whom correspondence should be addressed. E-mail: mserrano{at}cnio.es.

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 healthy concentrations. 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 use of gene expression profiling of circulating plasma RNA to find cancer markers of potential clinical value.