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Low RAI2 expression is a marker of poor prognosis in breast cancer

  • Preclinical study
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Retinoic acid-induced 2 (RAI2) has been shown to be a putative suppressor of the early hematogenous dissemination of tumor cells to the bone marrow in breast cancer. Here, we investigated the associations of RAI2 mRNA and protein expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up.

Methods

Invasive breast cancer tissues (n = 604) were analyzed for RAI2 mRNA expression. We examined the associations of clinicopathological factors with the expression levels of RAI2 mRNA in these samples. We also analyzed RAI2 protein expression by immunohistochemistry in invasive breast cancer tissues (n = 422).

Results

We identified significant positive associations between low expression of RAI2 mRNA and shorter disease-free survival (DFS), breast-cancer-specific survival (BCSS), and overall survival (OS) in breast cancer patients. We also identified significant positive associations between negative for RAI2 protein expression and shorter DFS, BCSS, and OS in breast cancer patients. Low RAI2 mRNA and negative for RAI2 protein expression were positively associated with larger tumor size, higher tumor grade, and ERα-negativity. Multivariate analyses indicated that not only RAI2 mRNA but also RAI2 protein expression were independent risk factors for both DFS and BCSS in breast cancer patients. The median follow-up periods were 10.3 and 9.3 years for the RAI2 mRNA and protein expression analyses, respectively.

Conclusions

Our findings suggest that RAI2 has a role in the metastasis of breast cancer, and that RAI2 expression could be a promising candidate biomarker of prognosis in breast cancer patients.

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Acknowledgements

We are grateful to the patients in this study. We thank Mrs. Makino and Ms. Ueki for excellent technical assistance. We also thank H. Nikki March, PhD, from Edanz Group (https://en-author-services.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) KAKENHI Grant Number 16K10468.

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Authors and Affiliations

  1. Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Sayaka Nishikawa, Yasuaki Uemoto, Tae-Sun Kim, Tomoka Hisada, Naoto Kondo, Yumi Wanifuchi-Endo, Takashi Fujita, Tomoko Asano, Yusuke Katagiri, Mitsuo Terada, Akiko Kato, Yu Dong & Tatsuya Toyama

  2. Advanced Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 647-8601, Japan

    Hiroshi Sugiura

  3. Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Katsuhiro Okuda

  4. Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Hiroyuki Kato & Satoru Takahashi

  5. Clinical Research Management Center, Nagoya City University Hospital, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Satoshi Osaga

  6. Department of Breast and Endocrine Surgery, Toyokawa City Hospital, 23 Noji, Yawata-cho, Toyokawa, 442-8561, Japan

    Sayaka Nishikawa

Authors
  1. Sayaka Nishikawa
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  2. Yasuaki Uemoto
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  3. Tae-Sun Kim
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  4. Tomoka Hisada
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  6. Yumi Wanifuchi-Endo
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  12. Yu Dong
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  15. Hiroyuki Kato
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  16. Satoshi Osaga
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  17. Satoru Takahashi
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  18. Tatsuya Toyama
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Corresponding author

Correspondence to Tatsuya Toyama.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Institutional Review Board of Nagoya City University Graduate School of Medical Sciences. All tissue samples were provided by a biobank that is maintained by the Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, which conforms to the guidelines of the Declaration of Helsinki.

Informed consent

Written informed consent for the comprehensive research use of clinical samples was obtained from all patients involved in this study.

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Nishikawa, S., Uemoto, Y., Kim, TS. et al. Low RAI2 expression is a marker of poor prognosis in breast cancer. Breast Cancer Res Treat 187, 81–93 (2021). https://doi.org/10.1007/s10549-021-06176-w

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  • DOI: https://doi.org/10.1007/s10549-021-06176-w

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