Overexpression of long noncoding RNA PCAT-1 is a novel biomarker of poor prognosis in patients with colorectal cancer

Overexpression of long noncoding RNA PCAT-1 is a novel biomarker of poor prognosis in patients with colorectal cancer
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DOI:
10.1007/s12032-013-0588-6
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发表时间:
2013-06-01
期刊:
影响因子:
3.4
通讯作者:
Jia, Weihua
Jia, Weihua
中科院分区:
医学4区
文献类型:
--
作者:
Ge, Xiaosong;Chen, Yuanbin;Jia, Weihua

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长非编码RNA(LncRNA)正在成为人类癌症的关键分子。前列腺癌相关核糖核糖核酸转录因子1(PCAT-1)是最近发现的与人类前列腺癌进展有关的一种核糖核糖核酸。然而,PCAT-1能否作为预测结直肠癌(CRC)预后的新生物标志物尚不清楚。因此,我们开展了这项研究,以探讨PCAT-1的表达与结直肠癌进展的相关性。本研究采用实时定量聚合酶链式反应技术检测108例大肠癌组织和81例癌旁正常组织中PCAT-1的表达。此外,还检测了17例肿瘤组织和配对的正常组织中PCAT-1基因的拷贝数变化。结果显示,PCAT-1在结直肠癌组织中的表达显著高于正常组织(p<0.001),%(62/81)的结直肠癌组织中存在PCAT-1的过度表达(上调幅度超过50%)。此外,PCAT-1基因拷贝数的变化只解释了观察到的几个百分点的过度表达。此外,PCAT-1的表达与远处转移显著相关(p=0.04),但与其他临床特征无关。更重要的是,pCAT-1高表达的结直肠癌患者的总体生存率明显低于pCAT-1低表达的患者(p<0.001)。多变量COX回归分析显示PCAT-1过度表达是结直肠癌的独立预后因素(P=0.007,HR=3.12,95%CI=1.355-7.185)。综上所述,我们的结果提示PCAT-1的高表达与结直肠癌的进展有关,并可能成为结直肠癌患者预后不良的新的生物标志物。
Long noncoding RNAs (lncRNA) are emerging as key molecules in human cancer. Prostate cancer-associated ncRNA transcripts 1 (PCAT-1), a lncRNA, has been recently revealed involving in human prostate cancer progression. However, whether PCAT-1 could serve as novel biomarker to predict prognosis in colorectal cancer (CRC) or not is unknown. We therefore carried out the present study to explore the correlation between PCAT-1 expression and the progression of CRC. In this study, the expression of PCAT-1 in 108 cases of CRC tissues and matched 81 adjacent normal tissues were determined by quantitative real-time PCR. Furthermore, the copy number variation of PCAT-1 was also measured in 17 tumor tissues and matched normal tissues. Our results showed that PCAT-1 expression in CRC tissues was significantly upregulated compared with the matched normal tissues (p < 0.001) and the overexpression of PCAT-1(upregulated by more than 50 %) was found in 64 % (62/81) of CRC. Moreover, PCAT-1 gene copy number variation explains only a few percent of observed overexpression. In addition, there was a significant association between PCAT-1 expression and distant metastasis (p = 0.04), but not other clinical characteristics. More important, CRC patients with PCAT-1 higher expression have shown significantly poorer overall survival than those with lower PCAT-1 expression (p < 0.001). Also, multivariable Cox regression analysis identified PCAT-1 overexpression as an independent prognostic factor for CRC (p = 0.007, HR = 3.12 95 % CI = 1.355-7.185). In conclusion, our results suggest that high expression of PCAT-1 is involved in CRC progression and could be a novel biomarker of poor prognosis in patient with colorectal cancer.