Transforming acidic coiled-coil-containing protein 2 (TACC2) in human breast cancer, expression pattern and clinical/prognostic relevance.
Transforming acidic coiled-coil-containing protein 2 (TACC2) in human breast cancer, expression pattern and clinical/prognostic relevance.
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DOI：
10.1158/0008-5472.sabcs-09-3159
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发表时间：
2009-12
影响因子：
2.5
通讯作者：
Shan Cheng;A. Douglas-Jones;Xiaomei Yang;R. Mansel;W. Jiang
中科院分区：
文献类型：
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作者：
Shan Cheng;A. Douglas-Jones;Xiaomei Yang;R. Mansel;W. Jiang
TACC 2是转化酸性卷曲螺旋蛋白家族的成员，在细胞周期中与中心体-纺锤体装置相关。TACC 2基因主要在有丝分裂后组织中以各种剪接形式表达，包括心脏、肌肉、肾脏和脑。最近的研究表明，这个家族的成员，包括TACC 2，可能参与某些实体瘤的进展。本研究的目的是确定TACC 2在乳腺癌中的作用，并确定是否存在预后相关性。使用新鲜冷冻的原发性人乳腺癌组织（n=127）和非肿瘤性乳腺组织（n=33）。使用免疫组织化学染色（IHC）评估TACC 2的分布和位置。使用定量实时PCR测定TACC 2的转录水平。根据临床、病理和随访（10年）数据分析结果。统计学分析采用双样本t检验和Kaplan-Meier法。TACC 2蛋白在乳腺组织中的正常上皮细胞和癌细胞中均可见染色。TACC 2转录物的定量分析显示，与正常组织相比，肿瘤中的表达水平更高。与较低级别肿瘤相比，TACC 2表达在较高级别肿瘤中显著增加（3级对1级，p=0.046）。使用诺丁汉预后指数（NPI），TACC 2转录物在中度预后患者的肿瘤中显著高于预后良好的患者（p=0.045）。来自具有不良临床结果（具有转移、复发和乳腺癌相关死亡）的患者的样品中的表达高于来自保持无疾病的患者的那些。这反映在具有高TACC 2的患者的较短无病生存期（107（95%置信区间：91-122.8）个月）与具有低TACC 2转录物的患者的137（125-150.6）个月相比（p=0.019）。这项研究表明，TACC 2的表达增加与乳腺癌患者的预后不良相关。这表明TACC 2可能介导对乳腺癌细胞的致癌作用，并表明TACC 2可能是潜在的治疗靶点。
TACC2 is a member of the transforming acidic coiled-coil-containing protein family and is associated with the centrosome-spindle apparatus during cell cycling. The TACC2 gene is expressed in various splice forms predominantly in postmitotic tissues, including heart, muscle, kidney, and brain. Recent work has shown that members of this family, including TACC2, may be involved in the progression of certain solid tumours. The aim of the current study was to identify the role of TACC2 in breast cancer and to establish if a prognostic relevance existed. Fresh frozen primary human breast cancer tissues (n=127) and non-neoplastic mammary tissues (n=33) were used. The distribution and location of TACC2 was assessed using immunohistochemical staining (IHC). The transcript levels of TACC2 were determined using quantitative real-time PCR. The results were analyzed against the clinical, pathological and follow-up (10 years) data. Statistical analysis was by two-sample t-test and Kaplan-Meier method. TACC2 protein staining was seen in both normal epithelial cells and cancer cells in mammary tissues. Quantitative analysis of the TACC2 transcript revealed a higher level of expression in tumours compared with normal tissues. TACC2 expression was significantly increased in higher grade tumours compared to that in lower grade tumours (grade 3 vs. grade 1, p=0.046). Using the Nottingham Prognostic Index (NPI), TACC2 transcript was significantly higher in tumours from patients with a moderate prognosis than from those with a good prognosis (p=0.045). The expression in samples from patients with poor clinical outcome (with metastasis, recurrence and breast cancer related death) was higher than that in those from patients who remained disease free. This was reflected by a shorter disease-free survival for patients with high TACC2 (107 (95% confidence interval: 91-122.8) months compared with 137 (125-150.6) months for patients with low TACC2 transcripts (p=0.019). This study shows that increased expression of TACC2 correlates with poor prognosis in patients with breast cancer. This suggests that TACC2 may mediate an oncogenic effect on breast cancer cells and indicates that TACC2 may be a potential therapeutic target.