J Cancer 2018; 9(15):2631-2639. doi:10.7150/jca.24978 This issue

Research Paper

Serum and exosome long non coding RNAs as potential biomarkers for hepatocellular carcinoma

Li Sun1,2, Yingying Su2, Xiangxiang Liu1, Mu Xu1, Xiaoxiang Chen1, Yefei Zhu2, Zhirui Guo2, Tingting Bai2, Lin Dong1, Chenchen Wei2, Xiaoxiao Cai2, Bangshun He1, Yuqin Pan1✉, Huiling Sun1, Shukui Wang1✉

1. Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, China;
2. The Second Affiliated Hospital , Nanjing Medical University, Nanjing 210011, Jiangsu, China.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Sun L, Su Y, Liu X, Xu M, Chen X, Zhu Y, Guo Z, Bai T, Dong L, Wei C, Cai X, He B, Pan Y, Sun H, Wang S. Serum and exosome long non coding RNAs as potential biomarkers for hepatocellular carcinoma. J Cancer 2018; 9(15):2631-2639. doi:10.7150/jca.24978. Available from https://www.jcancer.org/v09p2631.htm

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Background: Hepatocellular carcinoma (HCC) is one of the most aggressive cancers, with limited new diagnostic and therapeutic measures. This study aimed to investigate the utility of specific serum and exosome lncRNAs as biomarkers for early diagnosis of HCC.

Methods: The relative expression levels of eight selected lncRNAs in serum were evaluated by quantitative reverse transcription-PCR (qRT-PCR) in the training and validation sets of HCC patients and matched healthy controls. Additionally, the stability, specificity and diagnostic efficiency of these lncRNAs were evaluated to determine their potential as biomarkers. The levels of the final validated lncRNAs in exosome and urine samples of 15 HCC patients and 15 healthy controls were examined for source and path analysis.

Results: LINC00161 was significantly upregulated in serum samples of HCC patients and showed excellent stability and specificity (P< 0.001, fold change=2.85). The area under the receiver operating characteristic (ROC) curve of the validated lncRNA signature was 0.794 (95% CI, 0.712-0.877). LINC00161 expression was detected in serum exosome, exosome-free, and urine samples, and its levels in serum exosome were upregulated in patients with HCC as compared to controls (P= 0.011, fold change=4.27).

Conclusions: Our results indicated that circulating exosomal LINC00161 in serum may be a novel biomarker for HCC. LINC00161 is derived from exosomes into serum and may at least be partly metabolized through urine.

Keywords: serum, exosome, long non coding RNAs, biomarker, hepatocellular carcinoma