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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

2318 - Epigenetic markers in circulating cell-free DNA for detection of early stage colorectal cancer

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Yanqun Liu

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

Y. Liu1, C.K. Tham2, S. Ong2, C.L. Tang1, Y. Zhao3

Author affiliations

  • 1 Colorectal Surgery, Singapore General Hospital, 169856 - Singapore/SG
  • 2 Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 3 Clinical research, Singapore General Hospital, 169856 - Singapore/SG
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Resources

Abstract 2318

Background

The detection of early stage colorectal cancer (CRC) significantly improves chances of a cure and is a key factor in reducing CRC mortality rates. Colonoscopy is currently the gold standard for CRC diagnosis, but a somewhat troublesome and invasive procedure makes its acceptance not high in the general public as a screening tool. Epigenetic silencing of tumor-related genes by promoter methylation is common in CRC, but no biomarker has been proven to be individually of sufficient sensitivity or specificity in routine clinical practice. Objective: To identify tumor-derived methylated genes in the serum of stage IIA CRC and assessed their diagnostic potentials for early stage of colorectal cancer.

Methods

In this prospective study, DNA methylation levels were measured by quantitative methylation-specific PCR. Seven genes were screened in an exploratory set of case-control serum samples. Promising methylation markers were selected and verified in the serum of a test set compromising 60 stage IIA CRC and 60 age-gender-matched healthy controls. Receiver operating characteristic curve (ROC) was constructed for assessment of assay performance.

Results

Serum methylation levels of TAC1, EYA4 and SST were significantly higher in stage IIA patients as compared to healthy controls (all P < 0.001, Mann-Whitney U test). Area under the receiver operating curve (AUC) using serum methylation of TAC1 and EYA4 was 0.76 [95% confidence interval (CI), 0.68-0.85] and 0.73 (95% CI, 0.64-0.82), respectively. At a specificity of 85%, the assay sensitivity of TAC1 and EYA4 was 58.3% and 43.3%, respectively. Combination of serum methylation levels of EYA4 and SST improved the assay sensitivity to 52.5%. With TAC1 and SST being investigated in tumor DNA as well, we noticed that methylation of both genes in the serum DNA always mirrored that of tumor DNA, exhibiting 100% concordance.

Conclusions

Serum methylation levels of TAC1, EYA4 and SST might be useful for minimally invasive detection of early stage of colorectal cancer. Validation study in larger and independent cohorts is necessary.

Clinical trial identification

Legal entity responsible for the study

Singapore General Hospital.

Funding

National Medical Research Council, Singapore.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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