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.
Highlights
Hepatocellular carcinoma (HCC) has an extremely poor prognosis and is the fifth most common cancer in men and the ninth in women worldwide
MiR-34a and miR498 were further analyzed in an independent cohort of 106 HCC patients to determine whether they could serve as potential serum biomarkers to predict bone metastasis (BM)
The results of the univariate analyses revealed that serum miR-34a (P=0.002), serum miR-498 (P=0.038), tumor differentiation (P=0.011), tumor number (P=0.035), vascular invasion (P=0.005), and Barcelona Clinic Liver Cancer (BCLC) stage (P=0.002) were risk factors for BM in HCC patients (Table 1)
Summary
Hepatocellular carcinoma (HCC) has an extremely poor prognosis and is the fifth most common cancer in men and the ninth in women worldwide. It is the second leading cause of cancer death in men and the sixth in women worldwide [1]. Bone is destroyed by osteoclasts, which can cause pathological fractures, severe pain, and other nerve compression syndromes [5]. If we can identify biomarkers to predict BM in HCC patients, we could take measures to reduce the probability that BM will develop and potentially enhance the quality of life for HCC patients
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