TY - JOUR
T1 - Serum microRNA-based prediction of responsiveness to eribulin in metastatic breast cancer
AU - Satomi-Tsushita, Natsuko
AU - Shimomura, Akihiko
AU - Matsuzaki, Juntaro
AU - Yamamoto, Yusuke
AU - Kawauchi, Junpei
AU - Takizawa, Satoko
AU - Aoki, Yoshiaki
AU - Sakamoto, Hiromi
AU - Kato, Ken
AU - Shimizu, Chikako
AU - Ochiya, Takahiro
AU - Tamura, Kenji
N1 - Funding Information:
Serum samples used in this study were obtained from the National Cancer Center Biobank, which is supported by the National Cancer Center Research and Development Fund (29-A-1). This study was financially supported through a “Development of Diagnostic Technology for Detection of miRNA in Body Fluids” grant from the Japan Agency for Medical Research and Development (18ae0101013h0005). The authors thank Tomomi Fukuda, Takumi Sonoda, Hiroko Tadokoro, Megumi Miyagi and Tatsuya Suzuki for performing the microarray assays, Makiko Ichikawa and Satoshi Kondou for technical support, Noriko Abe for the management of serum samples, Michiko Ohori for the management of personal information, Hitoshi Fujimiya for developing in-house analytic tools and Kazuki Sudo for independent confirmation of participant eligibility.
Publisher Copyright:
© 2019 Satomi-Tsushita 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 - 2019/9/1
Y1 - 2019/9/1
N2 - The identification of biomarkers for predicting the responsiveness to eribulin in patients with metastatic breast cancer pretreated with an anthracycline and a taxane remains an unmet need. Here, we established a serum microRNA (miRNA)-based prediction model for the emergence of new distant metastases after eribulin treatment. Serum samples were collected from metastatic breast cancer patients prior to eribulin treatment and comprehensively evaluated by miRNA microarray. The prediction model for estimating eribulin efficacy was established using the logistic LASSO regression model. Serum samples were collected from 147 patients, of which 52 developed at least one new distant metastasis after eribulin monotherapy and 95 did not develop new distant metastases. A combination of eight serum miRNAs (miR-4483, miR-8089, miR-4755-3p, miR-296-3p, miR-575, miR-4710, miR-5698 and miR-3160-5p) predicted the appearance of new distant metastases with an area under the curve of 0.79, sensitivity of 0.69 and specificity of 0.82. The serum levels of miR-8089 and miR-5698 were significantly associated with overall survival after the initiation of eribulin treatment. The present study provides evidence that serum miRNA profiling may serve as a biomarker for the responsiveness to eribulin and for predicting the development of new distant metastases in metastatic breast cancer.
AB - The identification of biomarkers for predicting the responsiveness to eribulin in patients with metastatic breast cancer pretreated with an anthracycline and a taxane remains an unmet need. Here, we established a serum microRNA (miRNA)-based prediction model for the emergence of new distant metastases after eribulin treatment. Serum samples were collected from metastatic breast cancer patients prior to eribulin treatment and comprehensively evaluated by miRNA microarray. The prediction model for estimating eribulin efficacy was established using the logistic LASSO regression model. Serum samples were collected from 147 patients, of which 52 developed at least one new distant metastasis after eribulin monotherapy and 95 did not develop new distant metastases. A combination of eight serum miRNAs (miR-4483, miR-8089, miR-4755-3p, miR-296-3p, miR-575, miR-4710, miR-5698 and miR-3160-5p) predicted the appearance of new distant metastases with an area under the curve of 0.79, sensitivity of 0.69 and specificity of 0.82. The serum levels of miR-8089 and miR-5698 were significantly associated with overall survival after the initiation of eribulin treatment. The present study provides evidence that serum miRNA profiling may serve as a biomarker for the responsiveness to eribulin and for predicting the development of new distant metastases in metastatic breast cancer.
UR - http://www.scopus.com/inward/record.url?scp=85071755099&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071755099&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0222024
DO - 10.1371/journal.pone.0222024
M3 - Article
C2 - 31483849
AN - SCOPUS:85071755099
SN - 1932-6203
VL - 14
JO - PloS one
JF - PloS one
IS - 9
M1 - e0222024
ER -
