Research Paper Volume 12, Issue 7 pp 6067—6088

Identification of an exosomal long non-coding RNAs panel for predicting recurrence risk in patients with colorectal cancer

Yanli Zhang 2, , Hui Liu 1, , Xinfeng Liu 2, , Yulian Guo 3, , Yanlei Wang 4, , Yonggang Dai 2, , Jinhua Zhuo 2, , Bing Wu 2, , Hongchun Wang 1, , Xin Zhang 1, ,

  • 1 Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
  • 2 Department of Clinical Laboratory, Shandong Provincial Third Hospital, Jinan 250031, Shandong Province, China
  • 3 Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
  • 4 Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China

received: November 11, 2019 ; accepted: February 24, 2020 ; published: April 4, 2020 ;

https://doi.org/10.18632/aging.103006
How to Cite

Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.

Abbreviations

CRC: colorectal cancer; TNM: tumor-node-metastasis; AJCC: American Joint Committee on Cancer; lncRNAs: long non-coding RNAs; GLCC1: glycolysis-associated lncRNA of CRC 1; LNRRIL6: long non-coding RNA regulating IL-6 transcription; NEAT1: nuclear-enriched abundant transcript 1; exolncRNAs: exosomal lncRNAs; RT-qPCR: reverse transcription real-time quantitative polymerase chain reaction; cDNA: complementary DNA; CEA: carcinoembryonic antigen; CA19-9: carbohydrate antigen 19-9; ROC: receiver operating characteristic; RFS: recurrence free survival; OS: overall survival; AUC: area under the ROC curve; TAT: turn-around time.