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A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer.

Publication ,  Journal Article
Low, YS; Blöcker, C; McPherson, JR; Tang, SA; Cheng, YY; Wong, JYS; Chua, C; Lim, TKH; Tang, CL; Chew, MH; Tan, P; Tan, IB; Rozen, SG; Cheah, PY
Published in: Cancer Lett
September 10, 2017

Approximately 20% early-stage (I/II) colorectal cancer (CRC) patients develop metastases despite curative surgery. We aim to develop a formalin-fixed and paraffin-embedded (FFPE)-based predictor of metastases in early-stage, clinically-defined low risk, microsatellite-stable (MSS) CRC patients. We considered genome-wide mRNA and miRNA expression and mutation status of 20 genes assayed in 150 fresh-frozen tumours with known metastasis status. We selected 193 genes for further analysis using NanoString nCounter arrays on corresponding FFPE tumours. Neither mutation status nor miRNA expression improved the estimated prediction. The final predictor, ColoMet19, based on the top 19 genes' mRNA levels trained by Random Forest machine-learning strategy, had an estimated positive-predictive-value (PPV) of 0.66. We tested ColoMet19 on an independent test-set of 131 tumours and obtained a population-adjusted PPV of 0.67 indicating that early-stage CRC patients who tested positive have a 67% risk of developing metastases, substantially higher than the metastasis risk of 40% for node-positive (Stage III) patients who are generally treated with chemotherapy. Predicted-positive patients also had poorer metastasis-free survival (hazard ratios [HR] = 1.92, design-set; HR = 2.05, test-set). Thus, early-stage CRC patients who test positive may be considered for adjuvant therapy after surgery.

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Published In

Cancer Lett

DOI

EISSN

1872-7980

Publication Date

September 10, 2017

Volume

403

Start / End Page

13 / 20

Location

Ireland

Related Subject Headings

  • Transcriptome
  • Tissue Fixation
  • Time Factors
  • Risk Factors
  • Risk Assessment
  • Reproducibility of Results
  • ROC Curve
  • RNA, Messenger
  • Proportional Hazards Models
  • Predictive Value of Tests
 

Citation

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Low, Y. S., Blöcker, C., McPherson, J. R., Tang, S. A., Cheng, Y. Y., Wong, J. Y. S., … Cheah, P. Y. (2017). A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer. Cancer Lett, 403, 13–20. https://doi.org/10.1016/j.canlet.2017.05.031
Low, Yee Syuen, Christopher Blöcker, John R. McPherson, See Aik Tang, Ying Ying Cheng, Joyner Y. S. Wong, Clarinda Chua, et al. “A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer.Cancer Lett 403 (September 10, 2017): 13–20. https://doi.org/10.1016/j.canlet.2017.05.031.
Low, Yee Syuen, et al. “A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer.Cancer Lett, vol. 403, Sept. 2017, pp. 13–20. Pubmed, doi:10.1016/j.canlet.2017.05.031.
Low YS, Blöcker C, McPherson JR, Tang SA, Cheng YY, Wong JYS, Chua C, Lim TKH, Tang CL, Chew MH, Tan P, Tan IB, Rozen SG, Cheah PY. A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer. Cancer Lett. 2017 Sep 10;403:13–20.
Journal cover image

Published In

Cancer Lett

DOI

EISSN

1872-7980

Publication Date

September 10, 2017

Volume

403

Start / End Page

13 / 20

Location

Ireland

Related Subject Headings

  • Transcriptome
  • Tissue Fixation
  • Time Factors
  • Risk Factors
  • Risk Assessment
  • Reproducibility of Results
  • ROC Curve
  • RNA, Messenger
  • Proportional Hazards Models
  • Predictive Value of Tests