title: MicroRNA-34a expression levels in serum and intratumoral tissue can predict bone metastasis in patients with hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Zuo-Lin
authors.initials: ZL
authors.lastname: Xiang
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.affiliation: Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhao-Chong
authors.initials: ZC
authors.lastname: Zeng
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000209:etiology / Q000556:secondary*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000097:blood / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness
chemical_list: D014408:Biomarkers, Tumor; C522425:MIRN34 microRNA, human; D035683:MicroRNAs
keywords: bone metastasis; hepatocellular carcinoma; microRNA-34a; serum; tissue microarray