Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, hahid Beheshti University of Medical Sciences, Tehran, Iran.
Colorectal Division of Department of Surgery, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Cell Biochem. 2019 Sep;120(9):14780-14790. doi: 10.1002/jcb.28739. Epub 2019 Apr 16.
Like other noncoding RNAs (ncRNAs), dysregulation of long ncRNAs (lncRNAs) has been associated with various clinicopathological features of colorectal cancer (CRC) patients such as lymph node metastasis (LNM). Recently, three aberrant expressed oncogenic lncRNA (onco-lncRNAs), including HOXA transcript at the distal tip (HOTTIP), plasmacytoma variant translocation 1 (PVT1), and urothelial carcinoma associated 1 (UCA1) have been reported in LNM. Herein, we compared the diagnostic performance of these lncRNAs as individual biomarkers and as a discriminating panel between LNM CRC patients, nonmetastatic lymph nodes (NLN) and normal healthy subjects. The lncRNAs expression level was measured by quantitative real-time PCR and analyzed by the Mann-Whitney U test. The receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic power. The Kaplan-Meier survival analysis was performed to outline the overall survival (OS) of CRC patients with an abnormal level of lncRNAs. The area under the ROC curve (AUC) of the overexpressed HOTTIP (0.7817; 95% CI, 0.6809-0.8824), PVT1 (0.8559; 95% CI, 0.7737-0.9382), and UCA1 (0.8135; 95% CI, 0.722-0.9051) introduced them as individual CRC biomarkers. As a predictive panel, the AUC values of the HOTTIP, PVT1, and UCA1 for training set were 0.9256 (95% CI, 0.8634-0.9879; all CRCs), 0.8708 (95% CI, 0.7709-0.9378; NLN) and 0.9804 (95% CI, 0.9585-0.9998; LNM), and for validation set were 0.9286 (95% CI, 0.8752-0.9820; all CRCs), 0.8911 (95% CI, 0.8238-0.9585; NLN), and 0.9833 (95% CI, 0.9642-1.002; LNM), respectively. Also, HOTTIP/PVT1/UCA1 panel dysregulation had a marked correlation with patient's OS in training set (logrank test P = 0.0121; hazard ratio [HR], 0.1225; 95% confidence interval [CI], 0.02376-0.6312), and in validation set (logrank test P < 0.0001, HR, 0.2003; 95% CI, 0.08942-0.4486). These data showed that the combination of HOTTIP, PVT1, and UCA1 as a predictive panel, has a better diagnostic performance than each of these lncRNAs individually, and could be used for the screening of patients with advanced CRC.
像其他非编码 RNA(ncRNAs)一样，长链非编码 RNA(lncRNAs)的失调与结直肠癌(CRC)患者的各种临床病理特征有关，如淋巴结转移(LNM)。最近，三种异常表达的致癌 lncRNA(oncogenic-lncRNAs)，包括 HOXA 转录远端末端(HOTTIP)、浆细胞瘤变异易位 1(PVT1)和尿路上皮癌相关 1(UCA1)，已在 LNM 中报道。在此，我们比较了这些 lncRNAs 作为个体生物标志物和作为区分 LNM CRC 患者、非转移性淋巴结(NLN)和正常健康受试者的鉴别面板的诊断性能。通过定量实时 PCR 测量 lncRNAs 的表达水平，并通过曼-惠特尼 U 检验进行分析。应用受试者工作特征(ROC)曲线分析评估诊断能力。Kaplan-Meier 生存分析用于概述 lncRNAs 水平异常的 CRC 患者的总生存期(OS)。过表达 HOTTIP(0.7817；95%置信区间，0.6809-0.8824)、PVT1(0.8559；95%置信区间，0.7737-0.9382)和 UCA1(0.8135；95%置信区间，0.722-0.9051)的 ROC 曲线下面积(AUC)将它们作为个体 CRC 生物标志物引入。作为预测性面板，HOTTIP、PVT1 和 UCA1 的 AUC 值对于训练集分别为 0.9256(95%置信区间，0.8634-0.9879；所有 CRC)、0.8708(95%置信区间，0.7709-0.9378；NLN)和 0.9804(95%置信区间，0.9585-0.9998；LNM)，对于验证集分别为 0.9286(95%置信区间，0.8752-0.9820；所有 CRC)、0.8911(95%置信区间，0.8238-0.9585；NLN)和 0.9833(95%置信区间，0.9642-1.002；LNM)。此外，HOTTIP/PVT1/UCA1 面板失调与训练集患者的 OS 具有显著相关性(logrank 检验 P=0.0121；风险比[HR]，0.1225；95%置信区间[CI]，0.02376-0.6312)，以及验证集(logrank 检验 P<0.0001，HR，0.2003；95%CI，0.08942-0.4486)。这些数据表明，HOTTIP、PVT1 和 UCA1 的组合作为一个预测性面板，比每个 lncRNA 单独具有更好的诊断性能，可用于筛选晚期 CRC 患者。
