Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Oncology. 2012;82(2):114-8. doi: 10.1159/000336479. Epub 2012 Feb 11.
The development of colorectal cancer (CRC) is characterized by multiple genetic alterations. Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed. It has recently been proven in cancer systems that differentially expressed T-UCRs could alter the functional characteristics of malignant cells. Genome-wide profiling revealed that T-UCRs have distinct signatures in human leukemia and carcinoma.
In our study, we examined the expression levels of uc.43, uc.73, uc.134, uc.230, uc.339, uc.388 and uc.399 in 54 samples of primary colorectal carcinomas and 15 samples of non-tumoral adjacent tissues by real-time PCR. T-UCR expression levels were also correlated with commonly used clinicopathological features of CRC.
Expression levels of uc.73 (p = 0.0139) and uc.388 (p = 0.0325) were significantly decreased in CRC tissue, and uc.73 indicated a positive correlation with overall survival (p = 0.0315). The lower expression of uc.388 was associated with the distal location of CRC (p = 0.0183), but no correlation of any evaluated T-UCR with clinical stage, grade and tumor diameter was observed.
Our preliminary results suggest that uc.73 and uc.388 could be potential diagnostic and prognostic biomarkers in CRC patients.
结直肠癌(CRC)的发生发展伴随着多种基因改变。转录超保守区(T-UCRs)是指在人类、大鼠和小鼠基因组的同源区域之间绝对保守且能被转录的长度超过 200bp 的 481 个序列的一个子集。最近在癌症系统中已经证实,差异表达的 T-UCR 可以改变恶性细胞的功能特征。全基因组分析显示 T-UCR 在人类白血病和癌中有独特的特征。
在我们的研究中,通过实时 PCR 检测了 54 例原发性结直肠癌组织和 15 例非肿瘤邻近组织样本中 uc.43、uc.73、uc.134、uc.230、uc.339、uc.388 和 uc.399 的表达水平。T-UCR 的表达水平也与 CRC 的常用临床病理特征相关。
uc.73(p=0.0139)和 uc.388(p=0.0325)在 CRC 组织中的表达水平显著降低,uc.73 与总生存期呈正相关(p=0.0315)。uc.388 的低表达与 CRC 的远端位置有关(p=0.0183),但没有观察到任何评估的 T-UCR 与临床分期、分级和肿瘤直径有关。
我们的初步结果表明,uc.73 和 uc.388 可能是 CRC 患者潜在的诊断和预后生物标志物。