Nishimoto Mayumi, Nishikawa Sayaka, Kondo Naoto, Wanifuchi-Endo Yumi, Hato Yukari, Hisada Tomoka, Dong Yu, Okuda Katsuhiro, Sugiura Hiroshi, Kato Hiroyuki, Takahashi Satoru, Toyama Tatsuya
Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences.
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences.
Jpn J Clin Oncol. 2019 Jun 1;49(6):567-575. doi: 10.1093/jjco/hyz029.
Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a key stress protein with tumor suppressor function. Several studies have demonstrated TP53INP1 downregulation in many cancers. In this study, we investigated the correlations of TP53INP1 mRNA expression in breast cancer tissues with prognosis and the correlations of microRNAs that regulate TP53INP1 expression in breast cancer patients with long follow-up.
A total of 453 invasive breast cancer tissues were analyzed for TP53INP1 mRNA expression. We examined correlations of clinicopathological factors and expression levels of TP53INP1 mRNA in these samples. The expressions of miR-155, miR-569 and markers associated with tumor-initiating capacity were also analyzed. The median follow-up period was 9.0 years.
We found positive correlations between low expression of TP53INP1 mRNA and shorter disease-free survival and overall survival in breast cancer patients (P = 0.0002 and P < 0.0001, respectively), as well as in estrogen receptor α (ERα)-positive patients receiving adjuvant endocrine therapy (P = 0.01 and P = 0.0008, respectively). No correlations were found in ERα-negative patients. Low TP53INP1 mRNA levels positively correlated with higher grade and ERα-negativity. Multivariate analysis indicated that TP53INP1 mRNA level was an independent risk factor for overall survival both in overall breast cancer patients (hazard ratio, 2.13; 95% confidence interval, 1.17-3.92) and ERα-positive patients (hazard ratio, 2.34; 95% confidence interval, 1.18-4.64).
We show that low expression of TP53INP1 is an independent factor of poor prognosis in breast cancer patients, especially ERα-positive patients. TP53INP1 might be a promising candidate biomarker and therapeutic target in ERα-positive breast cancer patients.
肿瘤蛋白53诱导核蛋白1（TP53INP1）是一种具有肿瘤抑制功能的关键应激蛋白。多项研究已证实TP53INP1在多种癌症中表达下调。在本研究中，我们调查了乳腺癌组织中TP53INP1 mRNA表达与预后的相关性，以及在长期随访的乳腺癌患者中调节TP53INP1表达的微小RNA之间的相关性。
共分析了453例浸润性乳腺癌组织的TP53INP1 mRNA表达。我们检查了这些样本中临床病理因素与TP53INP1 mRNA表达水平的相关性。还分析了miR-155、miR-569的表达以及与肿瘤起始能力相关的标志物。中位随访期为9.0年。
我们发现TP53INP1 mRNA低表达与乳腺癌患者较短的无病生存期和总生存期呈正相关（分别为P = 0.0002和P < 0.0001），在接受辅助内分泌治疗的雌激素受体α（ERα）阳性患者中也呈正相关（分别为P = 0.01和P = 0.0008）。在ERα阴性患者中未发现相关性。TP53INP1 mRNA低水平与更高的分级和ERα阴性呈正相关。多变量分析表明，TP53INP1 mRNA水平是总体乳腺癌患者（风险比，2.13；95%置信区间，1.17 - 3.92）和ERα阳性患者（风险比，2.34；95%置信区间，1.18 - 4.64）总生存期的独立危险因素。
我们表明TP53INP1低表达是乳腺癌患者，尤其是ERα阳性患者预后不良的独立因素。TP53INP1可能是ERα阳性乳腺癌患者有前景的候选生物标志物和治疗靶点。
