The combination of strong immunohistochemical mtTFA expression and a high survivin index predicts a shorter disease-specific survival in pancreatic ductal adenocarcinoma
The combination of strong immunohistochemical mtTFA expression and a high survivin index predicts a shorter disease-specific survival in pancreatic ductal adenocarcinoma
复制标题
DOI：
10.14670/hh-30.193
复制
发表时间：
2015-02-01
影响因子：
2
通讯作者：
Yamada, Sohsuke
中科院分区：
文献类型：
--
作者：
Kimura, Tomoko;Kitada, Shohei;Yamada, Sohsuke
线粒体转录因子A （mtTFA）在线粒体DNA的转录和维持中起着至关重要的作用。mtTFA在多种实体肿瘤中高表达，并与癌细胞存活/凋亡和生长密切相关。然而，其在胰腺导管腺癌（PAC）中的表达模式尚不清楚。此外，我们的研究小组最近发现，凋亡相关基因的一个子集受到mtTFA的强烈调控，并且在survivin基因的启动子区域存在两个假定的mtTFA结合位点，survivin基因是凋亡抑制蛋白家族的成员。因此，我们利用70例手术切除PAC患者的石蜡包埋肿瘤样本，研究了免疫组化mtTFA表达和survivin指数与各种临床病理变量和预后的相关性。当>= 30%或10%的PAC细胞呈阳性染色时，mtTFA表达或survivin指数分别为强或高。强mtTFA表达和/或高survivin指数与病理上高肿瘤分级和晚期肿瘤分期有显著关系。此外，mtTFA与survivin的共表达量显著增高。单因素和多因素分析表明，mtTFA高表达组和高生存指数组的生存率都明显较短，尤其是在术后头两年。强mtTFA表达和高survivin指数的结合可能预示PAC患者预后不良，这些新的生物标志物可能为早期临床管理提供有用的信息。
Mitochondrial transcription factor A (mtTFA) plays a crucial role in both the transcription and maintenance of mitochondrial DNA. A high expression of mtTFA has been demonstrated in several solid tumors, and is closely associated with cancer cell survival/apoptosis and growth. However, its expression pattern in pancreatic ductal adenocarcinoma (PAC) remains to be elucidated. Additionally, our groups have recently revealed that a subset of apoptosis-related genes is strongly regulated by mtTFA, and that two putative mtTFA binding sites are present in the promoter region of the survivin gene, which is a member of the inhibitor-of-apoptosis protein family. We therefore investigated the correlation of the immunohistochemical mtTFA expression and the survivin index with various clinicopathological variables and the prognosis, using 70 paraffin-embedded tumor samples from patients with surgically-resected PAC. The mtTFA expression or survivin index was considered to be strong or high when >= 30% or 10% of the PAC cells showed positive staining, respectively. Strong mtTFA expression and/or a high survivin index was revealed to have a significant relationship to a pathologically high tumor grading and advanced tumor stage. Moreover, mtTFA showed significantly high co-expression with survivin. Univariate and multivariate analyses demonstrated that both the strong mtTFA expression and high survivin index groups had significantly shorter survival rates, especially within the first two years postoperatively. The combination of strong mtTFA expression and a high survivin index may predict a poor prognosis in patients with PAC, and these new biomarkers might offer useful information for the early clinical management.