Characterization of KIF20B as a novel prognostic biomarker and therapeutic target for breast cancer

Mbugua,Regina Wachuka; Takano,Atsushi; Tsevegjav,Bayarbat; Yokose,Tomoyuki; Yamashita,Toshinari; Miyagi,Yohei; Daigo,Yataro

doi:10.3892/ijo.2024.5631

Characterization of KIF20B as a novel prognostic biomarker and therapeutic target for breast cancer

Authors:
- Regina Wachuka Mbugua
- Atsushi Takano
- Bayarbat Tsevegjav
- Tomoyuki Yokose
- Toshinari Yamashita
- Yohei Miyagi
- Yataro Daigo
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Affiliations: Department of Medical Oncology and Cancer Center, Shiga University of Medical Science, Otsu, Shiga 520‑2192, Japan, Department of Pathology, Kanagawa Cancer Center, Yokohama, Kanagawa 241‑8515, Japan, Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa 241‑8515, Japan, Molecular Pathology and Genetics Division, Kanagawa Cancer Center, Research Institute, Yokohama, Kanagawa 241‑8515, Japan
Published online on: February 29, 2024 https://doi.org/10.3892/ijo.2024.5631
Article Number: 43

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Abstract

Despite advances in treatment and early detection, breast cancer remains one of the most common types of cancer and is the second leading cause of cancer death after lung cancer in women. Therefore, there is an urgent need to develop new biomarkers and therapeutic targets for the treatment of breast cancer. Based on gene expression profiles and subsequent screening performed in a preliminary study, kinesin family member 20B (KIF20B) was selected as a candidate target molecule, because it was highly and frequently expressed in all subtypes of breast cancer and barely detected in normal tissues. Reverse transcription‑quantitative PCR and western blotting revealed that KIF20B mRNA and protein expression levels were upregulated in most breast cancer cell lines but were scarcely expressed in normal mammary epithelial cells. Immunohistochemical staining of a tissue microarray showed that KIF20B was detected in 145 out of 251 (57.8%) breast cancer tissues. Strong KIF20B expression was significantly related to advanced pathological N stage. Moreover, patients with breast cancer and strong KIF20B expression exhibited a significantly worse prognosis than those with weak or negative KIF20B expression (P<0.0001, log‑rank test). In multivariate analysis, strong expression was an independent prognostic factor for patients with breast cancer. Furthermore, knockdown of KIF20B expression by small interfering RNA inhibited breast cancer cell proliferation and induced apoptosis. In addition, Matrigel cell invasion assays revealed that the invasiveness of breast cancer cells was significantly decreased by KIF20B silencing. Since KIF20B is an oncoprotein that is strongly expressed in highly malignant clinical breast cancer and serves a pivotal role in breast cancer cell proliferation, survival and invasion, KIF20B could be considered a candidate biomarker for prognostic prediction and a potential molecular target for developing new therapeutics, such as small molecule inhibitors, for a wide variety of breast cancers.

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