Genomic profiling of circulating plasma RNA for the analysis of cancer

Clin Chem. 2007 Oct;53(10):1860-3. doi: 10.1373/clinchem.2007.089201. Epub 2007 Aug 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / blood
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Biomarkers, Tumor / blood*
  • Carrier Proteins / blood
  • Carrier Proteins / genetics
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / surgery
  • DEAD-box RNA Helicases / blood
  • DEAD-box RNA Helicases / genetics
  • DNA-Binding Proteins
  • Feasibility Studies
  • Gene Expression Profiling*
  • Genomics
  • Humans
  • Neoplasm Proteins / blood*
  • Neoplasm Proteins / genetics
  • Oligonucleotide Array Sequence Analysis
  • RNA, Neoplasm / blood*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonucleoprotein, U2 Small Nuclear / blood
  • Ribonucleoprotein, U2 Small Nuclear / genetics
  • Ubiquitin-Conjugating Enzymes / blood
  • Ubiquitin-Conjugating Enzymes / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • Carrier Proteins
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • PCLAF protein, human
  • RNA, Neoplasm
  • Ribonucleoprotein, U2 Small Nuclear
  • endothelial PAS domain-containing protein 1
  • UBE2D3 protein, human
  • Ubiquitin-Conjugating Enzymes
  • DDX46 protein, human
  • DEAD-box RNA Helicases