First People's Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, China (mainland).
Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (mainland).
Med Sci Monit. 2019 Sep 19;25:7042-7051. doi: 10.12659/MSM.916314.
BACKGROUND Late diagnosis and metastasis are leading causes of the high mortality of colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) have been reported to play a critical role in the development and progression of CRC. This study aimed to explore the clinical significance of 2 novel lncRNAs - RP11-296E3.2 and LEF1-AS1 - including their expression pattern, as well as diagnostic and prognostic values, for metastatic CRC patients. MATERIAL AND METHODS lncRNAs expression was examined in tissues (91 cases) and plasma (60 cases) from CRC patients by real-time quantitative PCR (qRT-PCR), and the correlations between its expression and clinicopathological features and diagnosis values in metastasis were analyzed. TCGA datasets were further used to analyze their utility in prediction of overall survival (OS) and disease-free survival (DFS). ATP-based tumor chemosensitivity assay (ATP-TCA) was used to evaluated tumor chemoresistance. RESULTS Compared with adjacent normal tissues, RP11-296E3.2 was significantly downregulated while LEF1-AS1 was significantly upregulated in cancer tissues (p=0.0143, p=0.0322, respectively). High levels of RP11-296E3.2 and LEF1-AS1 in tissues and plasma were correlated with tumor metastasis (p=0.0488, p=0.0252 in tissues, p=0.0331, p=0.1862 in plasma, respectively). Further analysis showed that RP11-296E3.2 sensitivity and specificity in diagnosis of CRC metastasis is better than CEA in plasma (0.690 and 0.621, and 0.621 and 0.500, respectively), and the OS of metastatic CRC patients with higher LEF1-AS1 expression levels in tissues was short (log-rank p<0.05). CONCLUSIONS Our findings suggest that RP11-296E3.2 and LEF1-AS1 could separately serve as potential novel diagnosis and prognostic markers for CRC metastasis.
结直肠癌（CRC）死亡率高的主要原因是诊断延迟和转移。长链非编码 RNA（lncRNA）已被报道在 CRC 的发展和进展中发挥关键作用。本研究旨在探讨 2 种新型 lncRNA - RP11-296E3.2 和 LEF1-AS1 的临床意义，包括它们的表达模式以及对转移性 CRC 患者的诊断和预后价值。
通过实时定量 PCR（qRT-PCR）检测 CRC 患者组织（91 例）和血浆（60 例）中的 lncRNA 表达，并分析其表达与临床病理特征的相关性以及转移诊断价值。进一步使用 TCGA 数据集分析其在预测总生存期（OS）和无病生存期（DFS）中的应用。基于 ATP 的肿瘤化疗敏感性测定（ATP-TCA）用于评估肿瘤耐药性。
与相邻正常组织相比，癌组织中 RP11-296E3.2 明显下调，而 LEF1-AS1 明显上调（p=0.0143，p=0.0322）。组织和血浆中 RP11-296E3.2 和 LEF1-AS1 水平高与肿瘤转移相关（p=0.0488，p=0.0252 组织；p=0.0331，p=0.1862 血浆）。进一步分析表明，RP11-296E3.2 在诊断 CRC 转移中的敏感性和特异性优于血浆中的 CEA（分别为 0.690 和 0.621，0.621 和 0.500），组织中 LEF1-AS1 表达水平较高的转移性 CRC 患者的 OS 较短（对数秩检验 p<0.05）。
我们的研究结果表明，RP11-296E3.2 和 LEF1-AS1 可能分别作为 CRC 转移的潜在新型诊断和预后标志物。
