Expression of TACC3 and its relationship with epithelial mesenchymal transformation in gastric adenocarcinoma
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摘要:
目的 探讨转录相关酸性卷曲蛋白3(TACC3)在胃腺癌(GAC)中的表达及其与临床病理学参数间的关系，并研究TACC3在胃腺癌中与上皮-间质转化(EMT)间的关系。 方法 采用免疫组织化学方法对2013年10月—2014年10月蚌埠医学院第一附属医院病理科存档的113例胃腺癌标本及相应的癌旁组织标本进行TACC3、E-钙黏附蛋白(E-cadherin)和波形蛋白(Vimentin)的表达分析。 结果 TACC3、E-cadherin、Vimentin在胃腺癌标本和相应癌旁组织中的阳性表达率分别为67.3%、45.1%、50.4%和17.7%、69.9%、27.4%，差异有统计学意义。Kaplan-Meier生存分析表明，TACC3和Vimentin阳性表达的患者生存时间(OST)比阴性表达的患者短，差异有统计学意义(均P < 0.001)。E-cadherin表达阳性的患者生存时间高于阴性表达组(P < 0.001)。多因素分析显示TACC3和Vimentin的阳性表达及E-cadherin阴性表达是GAC的独立预后因素(均P < 0.05)；Spearman相关分析显示TACC3与Vimentin的表达呈正相关，E-cadherin与TACC3的表达呈负相关，E-cadherin和Vimentin的表达呈负相关(均P < 0.001)。 结论 TACC3的高表达在胃腺癌中与EMT及不良预后相关。TACC3有望成为胃腺癌靶向治疗的新靶点，同时TACC3早期检测结果有望成为评估胃腺癌患者转移和预后的指标之一。 -
关键词:
- 转录相关酸性卷曲蛋白3 /
- 上皮-间质转化 /
- 胃腺癌 /
- 预后
Abstract:Objective To investigate the expression of transforming acidic coiled-coil protein-3 (TACC3) in gastric adenocarcinoma (GAC) and explore the relationship between the expressions of TACC3 and epithelial-mesenchymal transition (EMT) and the clinicopathological parameters of patients. Methods A total of 113 GAC specimens and corresponding matched normal tissue specimens filed in Departments of Pathology, the First Affiliated Hospital of Bengbu Medical College from October 2013 to October 2014 were analysed for TACC3, E-cadherin and vimentin protein expressions by immunohistochemical staining. Results The positive expression rates of TACC3, E-cadherin and vimentin in GAC specimens and normal gastric tissues were 67.3%, 45.1%, 50.4% and 17.7%, 69.9%, 27.4%, respectively. The difference was statistically significant. Kaplan-Meier survival analysis showed that the survival time of patients with positive expression of TACC3 and vimentin was lower than that of patients with negative expression, and the difference was statistically significant (all P < 0.001). Patients who had positive expression of E-cadherin had a significantly higher OST than those with negative expression (P < 0.001). Multivariate analysis demonstrated that the positive expression of TACC3 and vimentin and the negative expression of E-cadherin were independent prognostic factors for GAC (all P < 0.05). Spearman correlation coefficient analysis showed that the expressions of TACC3 and vimentin were positively related. The relationship between E-cadherin and TACC3 was negatively correlated. The relationship between E-cadherin and vimentin was negatively correlated (all P < 0.001). Conclusion High expression of TACC3 is found to be related to EMT and poor prognosis in GAC. TACC3 is expected to become a new target for GAC targeted therapy, and early detection of TACC3 expression can be used to evaluate the metastasis and prognosis of GAC patients. -
图 1 TACC3在胃腺癌或相应癌旁组织中的免疫组化染色结果(ElivisionTM法，×200)
注：A为胃腺癌组织中的弱染色(浅黄色)；B为胃腺癌组织的中度染色(黄棕色)；C为胃腺癌组织中的强染色(棕色)；D为胃腺癌相应癌旁组织中的阴性表达。
Figure 1. TACC3 in gastric carcinoma and corresponding adjacent tissues of immunohistochemical staining results (Elivision TM method, ×200)
图 2 TACC3、E-cadherin和Vimentin的Kaplan-Meier生存分析曲线
注：A为胃腺癌患者生存时间与TACC3表达间的关系；B为胃腺癌患者生存时间与E-cadherin表达间的关系; C为胃腺癌患者生存时间与Vimentin表达间的关系。
Figure 2. Survival analysis curves of TACC3, E-cadherin, and Vimentin with Kaplan-Meier
表 1 不同临床特征胃腺癌患者胃腺癌组织中TACC3、E-cadherin、Vimentin表达情况比较(例)
Table 1. Different clinical features of gastric carcinoma patients with gastric adenocarcinoma tissues TACC3, E - cadherin, Vimentin expression in comparison (cases)
项目 TACC3 χ2值 P值 E-cadherin χ2值 P值 Vimentin χ2值 P值 + - + - + - 性别 1.963 0.161 1.713 0.191 0.169 0.681 男性 57 32 43 46 44 45 女性 19 5 8 16 13 11 年龄(岁) 0.459 0.498 2.086 0.149 0.003 0.953 ≤56 20 12 11 21 16 16 >56 56 25 40 41 41 40 分化程度 8.686 0.034 16.978 0.001 12.285 0.006 Ⅰ 2 2 2 2 1 3 Ⅱ 28 20 31 17 16 32 Ⅲ 15 10 11 14 16 9 差分化 31 5 7 29 24 12 TNM分期 8.164 0.004 8.740 0.003 8.882 0.003 0~Ⅱ 22 21 27 16 14 29 Ⅲ~Ⅳ 54 16 24 46 43 27 淋巴结转移 9.975 0.002 4.669 0.031 4.943 0.026 是 56 16 27 45 42 30 否 20 21 24 17 15 26 
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表 2 单因素生存分析结果
Table 2. Results of univariate survival analysis
项目 例数 术后总生存时间(x±s，月) log-rank χ2值 P值 TACC3 21.959 < 0.001 阴性 37 40.8±3.1 阳性 76 24.0±1.4 Vimentin 27.119 < 0.001 阴性 57 37.3±2.4 阳性 56 21.9±1.4 E-cadherin 27.889 < 0.001 阴性 51 22.5±1.5 阳性 62 37.5±2.4 性别 1.402 0.236 男 89 30.7±1.9 女 24 24.5±2.2 年龄(岁) 0.002 0.965 ≤56 32 28.7±2.3 >56 81 29.7±2.0 分化程度 26.267 < 0.001 Ⅰ 4 50.8±9.7 Ⅱ 48 33.3±2.1 Ⅲ 25 30.5±3.7 差分化 36 20.1±1.3 淋巴结转移 19.227 < 0.001 否 41 38.2±2.9 是 72 24.2±1.4 TNM分期 29.818 < 0.001 0~Ⅱ 43 40.8±3.0 Ⅲ~Ⅳ 70 22.7±1.6
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表 3 多因素生存分析结果
Table 3. Results of multivariate survival analysis
项目 B SE Wald χ2 P值 RR值 95% CI TACC3 -0.591 0.257 5.307 0.021 0.554 0.335~0.916 E-cadherin 0.491 0.242 4.120 0.042 1.635 1.017~2.628 Vimentin -0.520 0.236 4.849 0.028 0.594 0.374~0.944 分化程度 0.624 0.307 4.129 0.042 0.536 0.293~0.978 淋巴结转移 -0.523 0.257 4.419 0.021 0.554 0.335~0.916 TNM分期 0.746 0.254 6.621 0.003 2.108 1.281~3.467
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表 4 胃腺癌组织中TACC3、E-cadherin和Vimentin间的相关性分析
Table 4. Correlation analysis of TACC3, E-cadherin and Vimentin in gastric adenocarcinoma
项目 TACC3(例) r值 P值 E-cadherin(例) r值 P值 阴性 阳性 阴性 阳性 Vimentin 0.402 < 0.001 -0.488 < 0.001 阴性 29 27 17 39 阳性 8 49 45 12 E-cadherin -0.352 < 0.001 阴性 11 51 阳性 26 25
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