J Cancer 2020; 11(3):630-637. doi:10.7150/jca.33022

Research Paper

Serum exosomal miR-122 as a potential diagnostic and prognostic biomarker of colorectal cancer with liver metastasis

Li Sun1,2*, Xiangxiang Liu1*, Bei Pan1, Xiuxiu Hu1, Yefei Zhu2, Yingying Su2, Zhirui Guo2, Guoying Zhang1, Mu Xu1, Xueni Xu1, Huiling Sun1, Shukui Wang1✉

1. Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
2. Department of Laboratory Medicine, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
*These authors contribute to the study equally.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Sun L, Liu X, Pan B, Hu X, Zhu Y, Su Y, Guo Z, Zhang G, Xu M, Xu X, Sun H, Wang S. Serum exosomal miR-122 as a potential diagnostic and prognostic biomarker of colorectal cancer with liver metastasis. J Cancer 2020; 11(3):630-637. doi:10.7150/jca.33022. Available from http://www.jcancer.org/v11p0630.htm

File import instruction

Abstract

Background: Liver is the most common site for metastatic spread of CRC at the time of diagnosis which leads to high mortality. This study aimed to identify novel circulating exosomal miRNAs as biomarkers of colorectal cancer (CRC) with liver metastasis (LM).

Materials and methods: Candidate miRNAs were selected through integrated analysis of Gene Expression Omnibus (GEO) database as well as clinical samples. Exosomes isolated from serum and cultured media were identified by using transmission electron microscopy (TEM) and western blot. The expression levels and diagnostic value of candidate miRNAs were further tested and validated through qRT-PCR and receiver operating characteristic curve (ROC) analysis. The association of candidate miRNA expressions with patients' prognosis was analyzed with logistic regression and Cox proportional hazards regression models.

Results: After integrated analysis of three GEO datasets and clinical samples, miR-122 was discovered to be remarkably overexpressed in tissues of CRC patients. Then we revealed that elevated serum miR-122 was tumor-derived by being packaged into exosomes. The expressions of serum exosomal miR-122 were significantly upregulated in CRC patients, especially in those with LM. Serum exosomal miR-122 expressions could differentiate CRC patients with LM from healthy controls and patients without LM with area under the ROC curve (AUC) of 0.89 and 0.81. Uni- and multivariate logistic regression showed that serum exosomal miR-122 was an independent prognostic indicator of CRC patients.

Conclusions: Serum exosomal miR-122 was a novel potential diagnostic and prognostic biomarker in CRC patients with LM.

Keywords: colorectal cancer, serum, exosomes, miRNA, diagnosis, prognosis.