Sayaka Nishikawa1,2, Yasuaki Uemoto1, Tae-Sun Kim1, Tomoka Hisada1, Naoto Kondo1, Yumi Wanifuchi-Endo1, Takashi Fujita1, Tomoko Asano1, Yusuke Katagiri1, Mitsuo Terada1, Akiko Kato1, Yu Dong1, Hiroshi Sugiura3, Katsuhiro Okuda4, Hiroyuki Kato5, Satoshi Osaga6, Satoru Takahashi5, Tatsuya Toyama7. 1. Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. 2. Department of Breast and Endocrine Surgery, Toyokawa City Hospital, 23 Noji, Yawata-cho, Toyokawa, 442-8561, Japan. 3. Advanced Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 647-8601, Japan. 4. Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. 5. 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. 6. Clinical Research Management Center, Nagoya City University Hospital, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. 7. Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. t.toyama@med.nagoya-cu.ac.jp.
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.
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.
Authors: Stefan Werner; Benedikt Brors; Julia Eick; Elsa Marques; Vivian Pogenberg; Annabel Parret; Dirk Kemming; Antony W Wood; Henrik Edgren; Hans Neubauer; Thomas Streichert; Sabine Riethdorf; Upasana Bedi; Irène Baccelli; Manfred Jücker; Roland Eils; Tanja Fehm; Andreas Trumpp; Steven A Johnsen; Juha Klefström; Matthias Wilmanns; Volkmar Müller; Klaus Pantel; Harriet Wikman Journal: Cancer Discov Date: 2015-02-25 Impact factor: 39.397
Authors: S M Walpole; K T Hiriyana; A Nicolaou; E L Bingham; J Durham; M Vaudin; M T Ross; J R Yates; P A Sieving; D Trump Journal: Genomics Date: 1999-02-01 Impact factor: 5.736