LIN28 expression and prognostic value in hepatocellular carcinoma patients who meet the Milan criteria and undergo hepatectomy / 癌症

Stem cell marker LIN28, related closely with SOX2 and OCT4, has been studied as a biomarker for the maintainance of pluripotent cells in several malignancies. Our previous study showed that SOX2 and OCT4 were negative predictors for hepatocellular carcinoma (HCC). However, the predictive value of LIN28 in HCC outcome is still undetermined. We hypothesized that LIN28 may also play a role as a biomarker for HCC. To test this hypothesis, we examined the expression of LIN28 in 129 radically resected HCC tissues using reverse transcription-polymerase chain reaction and analyzed the association of LIN28 expression with clinicopathologic features and prognosis. Our study showed that LIN28 was expressed at a higher frequency in tumor tissues than in non-HCC tissues (45.0% vs. 21.7%, P = 0.020). Moreover, LIN28 expression was significantly increased in cases with large tumor size (P = 0.010). Univariate analysis did not reveal a significant correlation between LIN28 expression and overall survival or recurrence-free survival. For HCC patients who met the Milan criteria, stratified analysis revealed shorter overall survival (P = 0.007) and recurrence-free survival (P < 0.001) in those with detectable LIN28 expression compared to those with no detectable LIN28 expression. Furthermore, multivariate analysis revealed that LIN28 was a negative independent predictor for both overall survival (hazard ratio= 7.093, P = 0.017) and recurrence-free survival (hazard ratio=5.518, P = 0.004) in patients who met the Milan criteria. Taken together, our results suggest that LIN28 identifies low-risk and high-risk subsets of HCC patients meeting the Milan criteria who undergo hepatectomy.

OCT4 expression in hepatocellular carcinoma and its clinical significance / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Recently, many studies have focused on stem cells in hepatocellular carcinoma (HCC) and found some stem cell markers in HCC, which are associated with the prognosis. OCT4, as a member of the POU transcription factor family, is a key factor to maintain self-renewal and pluripotency of embryonic stem cells (ESCs). This study was to explore the expression of the ESCs marker OCT4A in HCC, and its correlations with clinicopathologic features and prognosis of HCC.</p><p><b>METHODS</b>OCT4A mRNA expression was detected in five liver cancer cell lines (SMMC-7721, BEL-7402, Hep-G2, MHCC97-L, and MHCC97-H), one immortalized liver cell line L-O2, tumor tissues with matched non-neoplastic liver tissues in 107 HCC patients, and normal liver tissues of 20 cases using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The correlations between OCT4A mRNA and clinicopathologic features and prognosis of HCC were analyzed.</p><p><b>RESULTS</b>OCT4A mRNA was detected in SMMC-7721, BEL-7402, Hep-G2, MHCC-97L, and MHCC-97H cells, but not in L-O2 cells. The positive rate of OCT4A mRNA expression was significantly higher in the HCC tissues than in the non-neoplastic liver tissues (72.0% vs. 30.8%, P<0.001). No OCT4A mRNA expression was found in the normal liver tissues. OCT4A mRNA expression was correlated with the tumor size, vascular invasion, and TNM stage (P<0.05). Kaplan-Meier survival curves showed that patients with positive expression of OCT4A mRNA had lower overall survival and disease-free survival rates.</p><p><b>CONCLUSIONS</b>OCT4A mRNA, which is highly expressed in a subset of liver cancer cell lines and HCC tissues, may be involved in the carcinogenesis of HCC. OCT4A mRNA may be a valuable biomarker for assessing the prognosis of HCC.</p>