HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients
HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients
复制标题
DOI：
10.1093/carcin/bgu055
复制
发表时间：
2014-07-01
期刊：
影响因子：
4.7
通讯作者：
Vodicka, Pavel
中科院分区：
文献类型：
--
作者：
Svoboda, Miroslav;Slyskova, Jana;Vodicka, Pavel
结直肠癌是导致死亡的主要肿瘤之一。对逆转这一趋势的预测和预后标志物的需求正在增加。长链非编码RNA HOTAIR（同源框转录反义基因间RNA）在肿瘤中的过度表达与不同癌症的预后不良和死亡率较高有关。我们分析了散发性CRC患者肿瘤和血液中HOTAIR的表达水平与其总生存期的关系，旨在评估CRC的替代预后标志物。组织供体组包括73例CRC患者的肿瘤和正常组织样本。献血员组为84例结直肠癌患者和40例健康对照者。患者的特征在于肿瘤淋巴结转移阶段，肿瘤分级，微卫星不稳定性和基质细胞的肿瘤渗透。通过实时定量PCR评估HOTAIR水平。CRC患者血液中HOTAIR的表达高于健康对照组（P = 0.0001），而CRC患者肿瘤和癌旁粘膜中HOTAIR水平无差异。HOTAIR水平与肿瘤呈正相关（R = 0.43，P = 0.03）。肿瘤中高HOTAIR水平与患者死亡率较高相关[考克斯比例风险，风险比= 4.4，95%置信区间：1.0-19.2，P = 0.046]。当考虑血液HOTAIR水平时，风险比甚至更高（风险比= 5.9，95%置信区间：1.3-26.1，P = 0.019）。原发肿瘤和CRC患者血液中HOTAIR相对表达上调与预后不良相关。我们的数据表明，HOTAIR血液水平可能作为一个潜在的替代预后标志物在散发性大肠癌。
Colorectal cancer (CRC) is one of the main causes of death of neoplasia. Demand for predictive and prognostic markers to reverse this trend is increasing. Long non-coding RNA HOTAIR (Homeobox Transcript Antisense Intergenic RNA) overexpression in tumors was previously associated with poor prognosis and higher mortality in different carcinomas. We analyzed HOTAIR expression levels in tumor and blood of incident sporadic CRC patients in relation to their overall survival with the aim to evaluate surrogate prognostic marker for CRC. Tissue donor group consisted of 73 CRC patients sampled for tumor and normal tissue. Blood donor group was represented by 84 CRC patients compared with 40 healthy controls. Patients were characterized for tumor-node-metastasis stage, tumor grade, microsatellite instability and tumor penetration by stromal cells. HOTAIR levels were assessed by real-time quantitative PCR. CRC patients had higher HOTAIR expression in blood than healthy controls (P = 0.0001), whereas there was no difference in HOTAIR levels between tumor and adjacent mucosa of CRC patients. HOTAIR levels positively correlated between blood and tumor (R = 0.43, P = 0.03). High HOTAIR levels in tumors were associated with higher mortality of patients [Cox's proportional hazard, hazard ratio = 4.4, 95% confidence interval: 1.0-19.2, P = 0.046]. The hazard ratio was even higher when blood HOTAIR levels were taken into account (hazard ratio = 5.9, 95% confidence interval: 1.3-26.1, P = 0.019). Upregulated HOTAIR relative expression in primary tumors and in blood of CRC patients is associated with unfavorable prognosis. Our data suggest that HOTAIR blood levels may serve as potential surrogate prognostic marker in sporadic CRC.