Brain metastasis-related microRNAs in patients with advanced breast cancer

Jun Sato; Akihiko Shimomura; Junpei Kawauchi; Juntaro Matsuzaki; Yusuke Yamamoto; Satoko Takizawa; Hiromi Sakamoto; Makoto Ohno; Yoshitaka Narita; Takahiro Ochiya; Kenji Tamura

doi:10.1371/journal.pone.0221538

Brain metastasis-related microRNAs in patients with advanced breast cancer

PLoS One. 2019 Oct 11;14(10):e0221538. doi: 10.1371/journal.pone.0221538. eCollection 2019.

Authors

Jun Sato¹, Akihiko Shimomura¹, Junpei Kawauchi^{2

3}, Juntaro Matsuzaki³, Yusuke Yamamoto³, Satoko Takizawa^{2

3}, Hiromi Sakamoto⁴, Makoto Ohno⁵, Yoshitaka Narita⁵, Takahiro Ochiya^{3

6}, Kenji Tamura¹

Affiliations

¹ Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
² Toray Industries, Inc., Kanagawa, Japan.
³ Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
⁴ Department of Biobank and Tissue Resources, Fundamental Innovative Oncology Core, National Cancer Center Research Institute, Tokyo, Japan.
⁵ Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁶ Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.

Abstract

Brain metastasis is a major distant metastasis occurring in patients with advanced breast cancer, and is associated with poor prognosis. MicroRNAs (miRNAs) have a strong influence on various oncological functions and have been reported as potential biomarkers for detecting distant metastasis. Specific biomarkers and unique miRNAs for brain metastasis have yet to be reported. The aim of this study was to identify novel miRNAs in serum, to assist in the diagnosis of brain metastasis in patients with advanced breast cancer. We retrospectively analyzed the medical records of patients with breast cancer and collected clinical data. In addition, we evaluated serum miRNA profiles in patients with breast cancer, with and without brain metastasis, using high-sensitivity microarrays. All patients underwent computed tomography or magnetic resonance imaging brain imaging tests. A total of 51 serum samples from patients with breast cancer and brain metastasis, stored in the National Cancer Center Biobank, were used, and 28 serum samples were obtained from controls without brain metastasis. Two miRNAs, miR-4428 and miR-4480, could significantly distinguish patients with brain metastasis, with area under the receiver operating characteristic curve (AUC) values of 0.779 and 0.781, respectively, while a combination of miR-4428 and progesterone receptor had an AUC value of 0.884. No significant correlations were identified between the expression levels of these two miRNAs in serum and clinical data. We conclude that serum miR-4428 and miR-4480 may be useful as biomarkers for predicting brain metastasis in patients with breast cancer.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor / blood*
Brain Neoplasms / blood*
Brain Neoplasms / pathology
Brain Neoplasms / secondary
Breast Neoplasms / blood*
Breast Neoplasms / pathology
Female
Humans
MicroRNAs / blood*
Middle Aged
Neoplasm Metastasis
RNA, Neoplasm / blood*

Substances

Biomarkers, Tumor
MicroRNAs
RNA, Neoplasm

Grants and funding

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. JS, MO, JM, TO, HS, KT received no specific funding for this work. AS reports personal fees from Chugai Pharmatheutical, personal fees from Novartis Pharmatheutical, personal fees from Pfizer, personal fees from Nippon Kayaku, personal fees and other from AstraZeneca, personal fees from Eisai, outside the submitted work. YN reports grants and personal fees from Chugai Pharmaceutical co., grants and personal fees from Ono Pharmaceutical co., grants and personal fees from Abbvie, grants and personal fees from Dainippon-Sumitomo, grants and personal fees from Daiichi-Sankyo, grants and personal fees from Eisai, grants and personal fees from Stella-pharma, grants and personal fees from Ohtuka, grants and personal fees from Meiji-seika, grants and personal fees from SBI pharma, outside the submitted work. ST reports personal fees from Toray Industries, Inc., during the conduct of the study; personal fees from Toray Industries, Inc., outside the submitted work. JK reports and Entity: Toray Industries, Inc.; personal Fees: employment. YY reports personal fees from Arkray, PNDeNA, Kewpie, outside the submitted work.