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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

Fingerprint

Neuregulin-1
colorectal neoplasms
Colorectal Neoplasms
Plasmas
Epidermal Growth Factor Receptor
Disease-Free Survival
Ligands
Immunosorbents
therapeutics
Assays
ROC Curve
Amphiregulin
Cetuximab
Therapeutics
Enzyme-Linked Immunosorbent Assay
enzyme-linked immunosorbent assay
Antibodies
Enzymes
antibodies

All Science Journal Classification (ASJC) codes

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

Cite this

Yonesaka, K., Takegawa, N., Satoh, T., Ueda, H., Yoshida, T., Takeda, M., ... Nakagawa, K. (2015). Combined analysis of plasma amphiregulin and heregulin predicts response to cetuximab in metastatic colorectal cancer. PloS one, 10(11), [e0143132]. https://doi.org/10.1371/journal.pone.0143132

Combined analysis of plasma amphiregulin and heregulin predicts response to cetuximab in metastatic colorectal cancer. / Yonesaka, Kimio; Takegawa, Naoki; Satoh, Taroh; Ueda, Hiroto; Yoshida, Takeshi; Takeda, Masayuki; Shimizu, Toshio; Chiba, Yasutaka; Okamoto, Isamu; Nishio, Kazuto; Tamura, Takao; Nakagawa, Kazuhiko.

In: PloS one, Vol. 10, No. 11, e0143132, 01.11.2015.

Research output: Contribution to journalArticle

Yonesaka, K, Takegawa, N, Satoh, T, Ueda, H, Yoshida, T, Takeda, M, Shimizu, T, Chiba, Y, Okamoto, I, Nishio, K, Tamura, T & Nakagawa, K 2015, 'Combined analysis of plasma amphiregulin and heregulin predicts response to cetuximab in metastatic colorectal cancer', PloS one, vol. 10, no. 11, e0143132. https://doi.org/10.1371/journal.pone.0143132
Yonesaka, Kimio ; Takegawa, Naoki ; Satoh, Taroh ; Ueda, Hiroto ; Yoshida, Takeshi ; Takeda, Masayuki ; Shimizu, Toshio ; Chiba, Yasutaka ; Okamoto, Isamu ; Nishio, Kazuto ; Tamura, Takao ; Nakagawa, Kazuhiko. / Combined analysis of plasma amphiregulin and heregulin predicts response to cetuximab in metastatic colorectal cancer. In: PloS one. 2015 ; Vol. 10, No. 11.
@article{8f27957846f64d7388358c6f713420d0,
title = "Combined analysis of plasma amphiregulin and heregulin predicts response to cetuximab in metastatic colorectal cancer",
abstract = "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.",
author = "Kimio Yonesaka and Naoki Takegawa and Taroh Satoh and Hiroto Ueda and Takeshi Yoshida and Masayuki Takeda and Toshio Shimizu and Yasutaka Chiba and Isamu Okamoto and Kazuto Nishio and Takao Tamura and Kazuhiko Nakagawa",
year = "2015",
month = "11",
day = "1",
doi = "10.1371/journal.pone.0143132",
language = "English",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=84957109194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84957109194&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0143132

DO - 10.1371/journal.pone.0143132

M3 - Article

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e0143132

ER -