Combined analysis of plasma amphiregulin and heregulin predicts response to cetuximab in metastatic colorectal cancer

Kimio Yonesaka, Naoki Takegawa, Taroh Satoh, Hiroto Ueda, Takeshi Yoshida, Masayuki Takeda, Toshio Shimizu, Yasutaka Chiba, Isamu Okamoto, Kazuto Nishio, Takao Tamura, Kazuhiko Nakagawa

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12 Citations (Scopus)


Background Amphiregulin, a ligand of the epidermal growth factor receptor (EGFR), is associated with the efficacy of cetuximab, an antibody against EGFR, as treatment for colorectal cancer (CRC). In contrast, the HER3 ligand heregulin correlates with cetuximab resistance. In this study, we evaluated how the combined levels of circulating amphiregulin and heregulin affect clinical outcomes in patients who receive cetuximab as therapy against advanced CRC. Methods Plasma levels of amphiregulin and heregulin were measured by enzyme-linked immunosorbent assay in 50 patients with CRC in a training cohort, and in 10 patients in a validation cohort. The combined expression was then assessed with clinical outcome after receiver operating characteristics analysis. Results Overall response rate was 26%, and median progression-free survival was 110 days in the training cohort. Patients with high amphiregulin and low heregulin had significantly higher objective response rate at 58% and significantly longer progression-free survival of 216 days. This result was confirmed in the validation cohort. Conclusion A subgroup of CRC patients with high amphiregulin and low heregulin respond to cetuximab therapy better than other patients.

Original languageEnglish
Article numbere0143132
JournalPloS one
Issue number11
Publication statusPublished - Nov 1 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General


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