Circulating tumor DNA sequencing for colorectal cancers: A comparative analysis of colon cancer and rectal cancer data

Cancer Biomark. 2019;26(3):313-322. doi: 10.3233/CBM-190257.

Abstract

Background: Circulating tumor DNA (ctDNA) has been recognized as a promising biomarker for colorectal cancer (CRC) early diagnosis and postoperative monitoring. However, we hypothesize that the clinical value of ctDNA sequencing may differ for colon cancer (CC) and rectal cancer (RC).

Methods: Forty-three patients with primary CRC were prospectively enrolled. Tumor tissue samples, paired preoperative plasma samples and a series of postoperative plasma samples were obtained. Mutations in each sample were identified and compared.

Results: For 73.0% patients, at least one concordant mutation was detected in both tumor tissue DNA and paired preoperative ctDNA. The mutation concordance rate were higher in CC patients compared to RC patients (92.3% vs 45.5%; p= 0.004). For early stage patients, the mutation concordance rate was 72.7%. The recurrence rate was 33.3% for patients with postoperative ctDNA positive mutations, and 3.4% for patients with negative ctDNA (HR 10.767; 95% CI 1.1-103.8; p= 0.040).

Conclusion: Liquid biopsy via ctDNA sequencing has great potential for the early detection and postoperative monitoring of CRC. The DNA of CC tissues is more likely to be released into blood than the DNA of RC tissues. This should be considered when diagnosing CRC patients with ctDNA sequencing technology.

Keywords: Circulating tumor DNA; colorectal cancer; early diagnosis; next generation sequencing; predicting recurrence.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / isolation & purification
  • Circulating Tumor DNA / blood*
  • Circulating Tumor DNA / genetics
  • Circulating Tumor DNA / isolation & purification
  • Colonic Neoplasms / blood
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / surgery
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Liquid Biopsy / methods
  • Male
  • Middle Aged
  • Mutation Rate
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / genetics
  • Prognosis
  • Prospective Studies
  • Rectal Neoplasms / blood
  • Rectal Neoplasms / diagnosis*
  • Rectal Neoplasms / genetics
  • Rectal Neoplasms / surgery

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA