Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Department of Breast and Endocrine Surgery, Toyokawa City Hospital, 23 Noji, Yawata-cho, Toyokawa, 442-8561, Japan.
Breast Cancer Res Treat. 2021 May;187(1):81-93. doi: 10.1007/s10549-021-06176-w. Epub 2021 Mar 29.
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.
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).
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.
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.
视黄酸诱导基因 2（RAI2）已被证明是乳腺癌中肿瘤细胞早期血源性播散到骨髓的潜在抑制因子。在这里，我们研究了 RAI2 mRNA 和蛋白表达与乳腺癌患者长期随访的临床病理因素和预后的关系。
分析了 604 例浸润性乳腺癌组织的 RAI2 mRNA 表达。我们检查了这些样本中 RAI2 mRNA 表达与临床病理因素的关系。我们还通过免疫组织化学分析了 422 例浸润性乳腺癌组织中的 RAI2 蛋白表达。
我们发现 RAI2 mRNA 低表达与乳腺癌患者无病生存（DFS）、乳腺癌特异性生存（BCSS）和总生存（OS）较短显著相关。我们还发现 RAI2 蛋白表达阴性与乳腺癌患者 DFS、BCSS 和 OS 较短显著相关。低 RAI2 mRNA 和 RAI2 蛋白表达阴性与肿瘤较大、肿瘤分级较高和 ERα 阴性呈正相关。多变量分析表明，不仅 RAI2 mRNA，而且 RAI2 蛋白表达都是乳腺癌患者 DFS 和 BCSS 的独立危险因素。RAI2 mRNA 和蛋白表达分析的中位随访时间分别为 10.3 年和 9.3 年。
我们的研究结果表明，RAI2 在乳腺癌的转移中起作用，RAI2 表达可能是乳腺癌患者预后有前途的候选生物标志物。
