Metastasis and Angiogenesis Research Group, University Department of Surgery, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, U.K.
Cancer Genomics Proteomics. 2010 Mar-Apr;7(2):67-73.
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.
TACC2 是转化酸性卷曲螺旋蛋白家族的成员，与细胞周期中的中心体-纺锤体装置有关。TACC2 基因以主要在有丝后组织（包括心脏、肌肉、肾脏和大脑）中表达的各种剪接形式表达。最近的工作表明，该家族的成员，包括 TACC2，可能参与某些实体瘤的进展。本研究的目的是确定 TACC2 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 TACC2 的分布和位置。使用定量实时 PCR 确定 TACC2 的转录水平。结果与临床、病理和随访（10 年）数据进行分析。统计分析采用两样本 t 检验和 Kaplan-Meier 法。在乳腺组织中，TACC2 蛋白染色可见于正常上皮细胞和癌细胞中。TACC2 转录本的定量分析显示，肿瘤中的表达水平高于正常组织。与低级别肿瘤相比，TACC2 在高级别肿瘤中的表达显著增加（3 级与 1 级，p=0.046）。使用诺丁汉预后指数（NPI），TACC2 转录本在预后中等的肿瘤中明显高于预后良好的肿瘤（p=0.045）。在临床预后不良（转移、复发和乳腺癌相关死亡）患者的样本中表达高于无病患者。对于高 TACC2 患者，无病生存期较短（107（95%置信区间：91-122.8）个月，而低 TACC2 转录本患者为 137（125-150.6）个月（p=0.019）。本研究表明，TACC2 的表达增加与乳腺癌患者的不良预后相关。这表明 TACC2 可能对乳腺癌细胞具有致癌作用，并表明 TACC2 可能是一个潜在的治疗靶点。
