Department of Clinical Laboratory, Shandong Provincial Third Hospital, Jinan 250031, Shandong Province, China.
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China.
Aging (Albany NY). 2020 Apr 4;12(7):6067-6088. doi: 10.18632/aging.103006.
Recurrence is a major cause of cancer-related deaths in colorectal cancer (CRC) patients, but the current strategies are limited to predict this clinical behavior. Our aim is to develop a recurrence prediction model based on long non-coding RNAs (lncRNAs) in exosomes of serum to improve the prediction accuracy. In discovery phase, 11 lncRNAs were found to be associated with CRC recurrence in tissues using high-throughput lncRNAs microarray and reverse transcription quantitative real-time PCR. And, 9 of them were correlated with their expression levels of serum exosomes. In training phase, a model based on 5-exosomal lncRNAs (exolncRNAs) panel was constructed, and showed high distinguish capability for recurrent CRC patients. ROC showed the panel was superior to serum CEA and CA19-9 in prediction of CRC recurrence. In both training and test sets, high-risk patients defined by the 5-exolncRNAs panel had poor recurrence free and overall survival. And, COX model showed it was an independent factor for CRC prognosis. Moreover, there was a significant relationship in detection of 5-exolncRNAs between plasma samples and paired serum samples. In summary, the 5-exolncRNAs panel robustly stratifies CRC patients' risk of recurrence, enabling more accurate prediction of prognosis.
复发是结直肠癌(CRC)患者癌症相关死亡的主要原因,但目前的策略仅限于预测这种临床行为。我们的目的是开发一种基于血清外泌体中长链非编码 RNA(lncRNA)的复发预测模型,以提高预测准确性。在发现阶段,使用高通量 lncRNA 微阵列和逆转录定量实时 PCR 发现 11 个 lncRNA 与组织中的 CRC 复发相关,其中 9 个与血清外泌体的表达水平相关。在训练阶段,构建了基于 5 个外泌体 lncRNA(exolncRNA)面板的模型,该模型对复发性 CRC 患者具有较高的鉴别能力。ROC 表明该模型在预测 CRC 复发方面优于血清 CEA 和 CA19-9。在训练集和测试集中,由 5-exolncRNA 面板定义的高危患者无复发生存率和总体生存率较差。COX 模型显示其是 CRC 预后的独立因素。此外,在检测血浆样本和配对血清样本中的 5-exolncRNAs 之间存在显著关系。总之,5-exolncRNA 面板能够可靠地区分 CRC 患者的复发风险,从而更准确地预测预后。