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Tumor Biology

, Volume 35, Issue 10, pp 9639–9647 | Cite as

Decreasing relapse in colorectal cancer patients treated with cetuximab by using the activating KRAS detection chip

  • Ming-Yii Huang
  • Hsueh-Chiao Liu
  • Li-Chen Yen
  • Jia-Yuan Chang
  • Jian-Jhang Huang
  • Jaw-Yuan Wang
  • Shiu-Ru Lin
Research Article

Abstract

The KRAS oncogene was among the first genetic alterations in colorectal cancer (CRC) to be discovered. Moreover, KRAS somatic mutations might be used for predicting the efficiency of anti-epidermal growth factor receptor therapeutic drugs. Because the KRAS mutations are similar in the primary CRC and/or the CRC metastasis, KRAS mutation testing can be performed on both specimen types. The purpose of this study was to investigate the clinical advantage of using a KRAS pathway-associated molecule analysis chip to analyze CRC patients treated with cetuximab. Our laboratory developed a KRAS pathway-associated molecule analysis chip and a weighted enzymatic chip array (WEnCA) technique, activating KRAS detection chip, which can detect KRAS mutation status by screening circulating cancer cells in the bloodstream. We prospectively enrolled 210 stage II–III CRC patients who received adjuvant oxaliplatin plus infusional 5-fluorouracil/leucovorin (FOLFOX)-4 chemotherapy with or without cetuximab. We compared the chip results of preoperative blood specimens with disease control status in these patients. Among the 168 CRC patients with negative chip results, 119 were treated with FOLFOX-4 plus cetuximab chemotherapy, and their relapse rate was 35.3 % (42/119). In contrast, the relapse rate was 71.4 % among the patients with negative chip results who received FOLFOX-4 treatment alone (35/49). Negative chip results were significantly correlated with better treatment outcomes in the FOLFOX-4 plus cetuximab group (P < 0.001). We suggest that the activating KRAS detection chip is a potential tool for predicting clinical outcomes in CRC patients following FOLFOX-4 treatment with or without cetuximab therapy.

Keywords

Colon cancer Activating KRAS detection chip Cetuximab Recurrence 

Abbreviations

CRC

Colorectal cancer

WEnCA

Weighted enzymatic chip array

5-FU

5-Fluorouracil

LV

Leucovorin

FOLFOX

Oxaliplatin plus infusional 5-fluorouracil/leucovorin

EGFR

Epidermal growth factor receptor

PCR

Polymerase chain reaction

FISH

Fluorescence in situ hybridization

CTCs

Circulating tumor cells

UICC

Union for International Cancer Control

TNM

Tumor-node-metastasis

NCCN

National Comprehensive Cancer Network

Notes

Acknowledgments

This work was supported by grants from the Excellence for Cancer Research Center Grant through funding by the Ministry of Health and Welfare, Taiwan, Republic of China (MOHW103-TD-B-111-05), the Kaohsiung Medical University Hospital (KMUH101-1M66, KMUH102-2M46), and the Grant of Biosignature in Colorectal Cancers, Academia Sinica, Taiwan. All authors read and approved the final manuscript. We would like to acknowledge the helpful comments on this paper received from our reviewers.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ming-Yii Huang
    • 1
    • 2
  • Hsueh-Chiao Liu
    • 3
    • 4
  • Li-Chen Yen
    • 3
  • Jia-Yuan Chang
    • 3
  • Jian-Jhang Huang
    • 3
  • Jaw-Yuan Wang
    • 6
    • 7
  • Shiu-Ru Lin
    • 5
  1. 1.Department of Radiation Oncology, Cancer CenterKaohsiung Medical University HospitalKaohsiungTaiwan
  2. 2.Department of Radiation Oncology, Faculty of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  3. 3.Personalized Medical Service Center, Division of Laboratory MedicineFooyin University HospitalPingtungTaiwan
  4. 4.Institute of Biomedical SciencesNational Sun Yat-San UniversityKaohsiungTaiwan
  5. 5.Division of Medical ResearchFooyin University HospitalPingtungTaiwan
  6. 6.Division of Gastrointestinal and General Surgery, Department of Surgery CancerKaohsiung Medical University HospitalKaohsiungTaiwan
  7. 7.Department of Surgery, Graduate Institute of Clinical Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan

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