TY - JOUR
T1 - Combined analysis of plasma amphiregulin and heregulin predicts response to cetuximab in metastatic colorectal cancer
AU - Yonesaka, Kimio
AU - Takegawa, Naoki
AU - Satoh, Taroh
AU - Ueda, Hiroto
AU - Yoshida, Takeshi
AU - Takeda, Masayuki
AU - Shimizu, Toshio
AU - Chiba, Yasutaka
AU - Okamoto, Isamu
AU - Nishio, Kazuto
AU - Tamura, Takao
AU - Nakagawa, Kazuhiko
N1 - Publisher Copyright:
© 2015 Yonesaka et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0143132
DO - 10.1371/journal.pone.0143132
M3 - Article
C2 - 26569500
AN - SCOPUS:84957109194
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 11
M1 - e0143132
ER -
