Research Papers:

This article has been corrected. Correction in: Oncotarget. 2019; 10:6398-6399.

MicroRNA-34a expression levels in serum and intratumoral tissue can predict bone metastasis in patients with hepatocellular carcinoma

Zuo-Lin Xiang, Xiao-Mei Zhao, Li Zhang, Ping Yang, Jia Fan, Zhao-You Tang and Zhao-Chong Zeng _

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Oncotarget. 2016; 7:87246-87256. https://doi.org/10.18632/oncotarget.13531

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Zuo-Lin Xiang1,*, Xiao-Mei Zhao1,*, Li Zhang1, Ping Yang1, Jia Fan2, Zhao-You Tang2, Zhao-Chong Zeng1

1Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China

2Department of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China

*These authors have contributed equally to this work

Correspondence to:

Zhao-Chong Zeng, email: [email protected]

Keywords: hepatocellular carcinoma, bone metastasis, microRNA-34a, serum, tissue microarray

Received: July 05, 2016     Accepted: November 07, 2016     Published: November 23, 2016


Hepatocellular carcinoma (HCC) patients with bone metastasis (BM) suffer from pain and other symptoms that significantly reduce their quality of life. We screened a microRNA (miRNA) microarray to identify potential serum biomarkers for BM in HCC patients. A miRNA microarray was used to screen for BM-related miRNAs in paired serum samples from HCC patients with BM and from HCC patients without BM. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to quantify candidate miRNAs in serum samples from 106 independent HCC patients. Levels of candidate miRNAs in tissue samples from an independent cohort of 296 HCC patients were evaluated by in situ hybridization and intratumoral tissue microarray. The migration and invasion capabilities of HCCLM3 and SMMC-7721 cells were evaluated following treatment with a mimic and an inhibitor of miR-34a. Ninety miRNAs were differentially expressed in sera from HCC patients with BM when compared with sera from non-BM HCC patients (P < 0.05). Only miR-34a and miR-498 had false discovery rates (FDRs) < 0.05. In cohorts of 106 and 296 HCC patients, we found that reduced serum and intratumoral miR-34a expression levels were independent risk factors for developing BM. Migration and invasion experiments indicated that a reverse correlation existed between miR-34a and HCC tumor migration and invasion. This study demonstrates the potential for the use of miR-34a as a serum and intratumoral tissue biomarker for predicting the risk of BM in HCC patients.

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