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Enhancing Detection of Circulating Tumor Cells with Activating KRAS Oncogene in Patients with Colorectal Cancer by Weighted Chemiluminescent Membrane Array Method

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

In 2008, the National Comprehensive Cancer Network suggested conducting a KRAS mutations test in metastatic colorectal cancer (mCRC) patients prior to administering therapy that uses anti-epidermal growth factor receptor (EGFR) monoclonal antibody. However, tests of KRAS mutations have been limited when traditional molecular techniques, such as polymerase chain reaction (PCR) combined direct sequencing, are used to obtain and analyze patients’ cancer tissues. If the primary tumor or metastatic tissues of patients with mCRC is unavailable, then such analysis will not be feasible. Our laboratory has successfully established a colorimetric membrane array analysis platform that could detect activating KRAS mutations from the peripheral blood of patients with various malignancies.

Methods

The current research aims to improve the above-mentioned technique not only by using chemiluminescence detection to replace color development, but also to add scores weighted according to the relevance of each gene to activating KRAS mutations.

Results

Our results show that the described weighted chemiluminescent membrane array (WCHMA) can detect circulating tumor cells (CTCs) harboring activating KRAS mutations in the peripheral blood in CRC. The sensitivity, specificity, and accuracy were 90.2, 94.9, and 93.5%, respectively, and the detection limitation was three colon tumor cells per millimeter of blood. The current study would significantly improve the detection sensitivity and accuracy over that of our previously designed membrane array method.

Conclusions

These findings also highlight the need to prompt further prospective studies on more cases of CRC to further establish the clinical relevance of activating KRAS mutation detection from peripheral blood in anti-EGFR-based chemotherapy that uses activating KRAS detection chips and the WCHMA analysis method.

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Acknowledgment

This work was supported by grants from the National Science Council of the Republic of China (NSC 96-2320-B-037-011-MY3).

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Authors and Affiliations

  1. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Ming-Je Yang PhD, Li-Chen Yen PhD & Jaw-Yuan Wang MD, PhD

  2. School of Environmental and Life Sciences, Fooyin University, Kaohsiung, Taiwan

    Hua-Hsien Chiu PhD

  3. Research and Development Headquarters, Fooyin University, Kaohsiung, Taiwan

    Hua-Hsien Chiu PhD

  4. Division of Colorectal Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan

    Hwei-Ming Wang MD

  5. School of Medical and Health Sciences, Fooyin University, Daliao Shiang, Kaohsiung County, Taiwan

    Der-An Tsao PhD & Shiu-Ru Lin PhD

  6. Division of Colon and Rectal Surgery, Fooyin University Hospital, Pingtung, Taiwan

    Chao-Peng Hsiao MD

  7. Gene Target Technology Co. Ltd, Kaohsiung, Taiwan

    Yi-Fang Chen PhD

  8. Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Jaw-Yuan Wang MD, PhD

  9. Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Jaw-Yuan Wang MD, PhD

  10. Department of Medical Genetics, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Jaw-Yuan Wang MD, PhD

  11. Department of Medical Research, Fooyin University Hospital, Pingtung, Taiwan

    Shiu-Ru Lin PhD

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  1. Ming-Je Yang PhD
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  2. Hua-Hsien Chiu PhD
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Corresponding author

Correspondence to Shiu-Ru Lin PhD.

Additional information

Ming-Je Yang and Hua-Hsien Chiu are contributed equally to this work

Jaw-Yuan Wang and Shiu-Ru Lin are contributed equally to this work

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Yang, MJ., Chiu, HH., Wang, HM. et al. Enhancing Detection of Circulating Tumor Cells with Activating KRAS Oncogene in Patients with Colorectal Cancer by Weighted Chemiluminescent Membrane Array Method. Ann Surg Oncol 17, 624–633 (2010). https://doi.org/10.1245/s10434-009-0831-8

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  • DOI: https://doi.org/10.1245/s10434-009-0831-8

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