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By using an expressed sequence tag bioinformatic algorithm, we identified that  Lin28 homolog B  ( Lin28B ) may have an oncofetal expression pattern which may facilitate detecting cancer cells in adults. It is also reported to be a potential marker for cancer stem cells. Therefore, we sought to verify oncofetal-stemness characters of  Lin28B  and test its potential as a circulating cancer stem cell-like marker in adult HCC patients.  Lin28B  mRNA was examined in a panel of fetal tissue, adult tissue and tumors.  Lin28B  was over-expressed or knocked down in HepG2 cells to evaluate its potential as a stem cell-like marker. RT-qPCR for  Lin28B  was performed in the peripheral blood mononuclear cells from patients with HCC receiving surgery (n=96) and non-HCC controls (n=60) and analyzed its clinical significance.  Lin28B  showed an oncofetal expression pattern. Its overexpression could upregulate stemness markers (OCT4, Nanog and SOX2) and enhance tumorsphere formation  in vitro .  Lin28B  knockdown had opposite effects. Circulating  Lin28B  was detected in peripheral blood mononuclear cells in 3 cases (5%) of non-HCC controls and 32 cases (33.3%) of HCC patients. In HCC patients, circulating  Lin28B  was associated with high tumor grade (P=0.046), large size (P=0.005), high AJCC stage (P=0.044) and BCLC stage (P=0.017). Circulating  Lin28B  was significantly associated with decreased recurrence-free survival (P<0.001). Circulating  Lin28B  separated early stage HCC into 2 recurrence-free survival curves (P=0.003). In multivariate analysis, circulating  Lin28B  was an independent variable associated with early recurrence (P=0.045) and recurrence in early stage HCC (P=0.006). In conclusion, the oncofetal gene  Lin28B  is a potential oncofetal cancer-stem-cell-like circulating tumor cell marker that correlates with HCC recurrence after hepatectomy. Circulating  Lin28B  could refine early AJCC stages. Our finding supports the possible use of a TNMC (C for circulating tumor cells) staging system in HCC.

Lin28B Is an Oncofetal Circulating Cancer Stem Cell-Like Marker Associated with Recurrence of Hepatocellular Carcinoma