Correlation between transcriptional expression of survivin isoforms and clinicopathological findings in human colorectal carcinomas.
Correlation between transcriptional expression of survivin isoforms and clinicopathological findings in human colorectal carcinomas.
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DOI：
10.3892/or.13.5.891
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发表时间：
2005-05
期刊：
影响因子：
4.2
通讯作者：
K. Suga;Tetsuhisa Yamamoto;Yoshitaka Yamada;S. Miyatake;T. Nakagawa;N. Tanigawa
中科院分区：
文献类型：
--
作者：
K. Suga;Tetsuhisa Yamamoto;Yoshitaka Yamada;S. Miyatake;T. Nakagawa;N. Tanigawa
Survivin是凋亡抑制蛋白（IAP）家族的新成员，在大多数类型的人类癌症中显著过表达，并被认为是抗癌治疗的潜在靶点。此外，最近还发现了survivin的两种剪接变体——survivin- 2b和survivin- deltaex3。然而，其剪接变异体在结直肠癌中的表达分析尚未见报道。因此，我们研究了survivin及其剪接变异体在人类结直肠癌中的转录水平，并分析了转录表达水平与病理结果的相关性。肿瘤组织样本来自1995年至1996年在大阪医科大学切除的52例结直肠癌患者。转录水平通过定量逆转录聚合酶链反应（RT-PCR）测量，使用survivin及其剪接变体特异性的引物对，然后通过甘油醛6-磷酸脱氢酶进行归一化。survivin及其剪接变异体的转录水平在肿瘤组织样本中显著较高，在正常组织样本中显著较低。此外，大约40%的正常组织样本没有任何survivin表达。survivin- 2b对survivin的相对表达量（survivin- 2b /survivin）在肿瘤组织中明显高于正常组织。相比之下，survivin- deltaex3 /survivin在肿瘤和正常样本中没有差异。当比较组织学疾病分期（I期和II期与III期和IV期）时，survivin及其剪接变异体的表达水平无显著差异。survivin- 2b /survivin在ⅲ期和ⅳ期的表达水平低于ⅰ期和ⅱ期。此外，高水平的survivin- 2b /survivin与较好的预后显著相关。本研究发现survivin及其剪接变异体在肿瘤组织中高表达，具有相对特异性，提示其在人类结直肠癌的进展中具有重要作用。
Survivin, a novel member of the inhibitor of apoptosis protein (IAP) family, has been markedly overexpressed in most types of human carcinoma, and recognized as a potential target in anticancer therapy. In addition, two splice variants of survivin, survivin-2B and survivin-deltaEx3, have recently been identified. However, expression analysis on its splice variants has not been reported in colorectal carcinomas. Therefore, we investigated the transcription levels of survivin and its splice variants in human colorectal carcinomas, and the correlation between transcript expression levels and pathological findings was analyzed. Tumor tissue samples were provided from 52 cases with colorectal adenocarcinoma resected at the Osaka Medical College from 1995 to 1996. Transcription levels were measured by performing quantitative reverse transcription-polymerase chain reaction (RT-PCR) using primer pairs specific for survivin and either of its splice variants, then normalized by the glyceraldehyde 6-phosphate dehydrogenase. The transcription levels of survivin and its splice variants were significantly higher in the tumor tissue samples, and significantly lower in the normal tissue samples. In addition, approximately 40% of the normal tissue samples did not have any survivin expression. The relative expression level of survivin-2B to survivin (survivin-2B/survivin) was significantly higher in the tumor tissue samples than in the normal ones. In contrast, survivin-deltaEx3/survivin revealed no difference between tumor and normal samples. When Comparing the histological disease stages (stage I and II vs. stage III and IV), there were no significant differences in the expression levels of survivin and its splice variants. The expression level of survivin-2B/survivin for stage III and IV was lower than the one for stage I and II. In addition, a higher level of survivin-2B/survivin significantly correlated with a better prognosis in the present series. The present study demonstrates high expression level of survivin and its splice variants, which is relatively specific in tumor tissue and suggests that they have important roles in the progression of human colorectal carcinomas.