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The effect of colonoscopy on whole blood gene expression profile: an experimental investigation for colorectal cancer biomarker discovery

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Gene expression profiling of whole blood is showing great promise for the discovery of novel biomarkers for colorectal cancer (CRC) detection. Given the relatively low incidence rate of CRC in the general population, most blood samples collected prior to a colonoscopy were confirmed to be noncancerous afterward. Previous studies have relied on blood samples collected after a colonoscopy to reach the sufficient number of CRC cases. The present study aimed to determine the colonoscopy-induced variability in the blood transcriptome and its potential impact on biomarker discovery.

Methods

Whole blood gene expression profiling was conducted using Affymetrix HG-U133Plus2 arrays. We analyzed 20 paired blood samples collected from healthy controls before and after colonoscopy, and 20 blood samples collected from CRC patients after colonoscopy.

Results

Utilizing hierarchical clustering analysis, samples collected before and after colonoscopy from the same subjects were closely clustered together, suggesting that the blood gene expression profiles primarily reflect the heterogeneity within each individual. A total of 914 genes were differentially expressed between controls and CRC patients, while gene expression did not differ between samples collected before and after colonoscopy. Using real-time PCR technology, we further validated six genes from published biomarkers in this study. Our results confirmed that the biomarkers identified in previous studies were not likely to be biased due to the colonoscopy effect.

Conclusions

Our results showed that the colonoscopy-induced variations were minute compared to individuals’ heterogeneity and disease-induced variations. These findings may serve as a basis for future development of blood-based transcriptomic biomarkers for the diagnosis and treatment of CRC.

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Abbreviations

CRC:

Colorectal cancer

FOBT:

Fecal occult blood test

RMA:

Robust multi-chip average

IQR:

Inter-quantile range

SAM:

Significance analysis of microarrays

DEG:

Differentially expressed gene

FDR:

False discovery rate

TNM:

Tumor node metastasis

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Acknowledgments

This study was funded in part by bioMerieux Company. This study was funded in part by the Science and Technology Commission of Shanghai Municipality, Grant Number 10DJ1400500.

Conflict of interest

Four authors (QHX, XY, FW and XM) are employees of bioMerieux Company.

Author information

Authors and Affiliations

  1. Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China

    Ye Xu, Qinghua Xu, Li Yang, Shujuan Ni, Cong Tan, Guoxiang Cai, Sanjun Cai & Xiang Du

  2. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

    Ye Xu, Li Yang, Guoxiang Cai & Sanjun Cai

  3. Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Shanghai, 200032, China

    Qinghua Xu, Shujuan Ni, Cong Tan & Xiang Du

  4. Institut Mérieux Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China

    Qinghua Xu, Fang Liu, Xun Ye, Fei Wu & Xia Meng

  5. bioMérieux (Shanghai) Co. Ltd, Shanghai, China

    Qinghua Xu, Xun Ye, Fei Wu & Xia Meng

  6. Institutes of Biomedical Sciences, Fudan University, Shanghai, China

    Shujuan Ni, Cong Tan & Xiang Du

  7. Institute of Pathology, Fudan University, Shanghai, China

    Shujuan Ni, Cong Tan & Xiang Du

Authors
  1. Ye Xu
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  2. Qinghua Xu
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  3. Li Yang
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  4. Fang Liu
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  5. Xun Ye
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  6. Fei Wu
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  7. Shujuan Ni
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  8. Cong Tan
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  9. Guoxiang Cai
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  10. Xia Meng
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  11. Sanjun Cai
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  12. Xiang Du
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Corresponding authors

Correspondence to Sanjun Cai or Xiang Du.

Additional information

Ye Xu, Qinghua Xu and Li Yang these authors contributed equally to this work.

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Xu, Y., Xu, Q., Yang, L. et al. The effect of colonoscopy on whole blood gene expression profile: an experimental investigation for colorectal cancer biomarker discovery. J Cancer Res Clin Oncol 141, 591–599 (2015). https://doi.org/10.1007/s00432-014-1837-6

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  • DOI: https://doi.org/10.1007/s00432-014-1837-6

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