Objective To summarize clinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC) expressing " stemness”-related markers. Method The clinical researches on HCC expressing " stemness”-related markers in recent years were reviewed. Results The HCC expressing " stemness”-related markers was the special subtype with the aggressive biological behavior as compared with the conventional HCC, which were associated with the increased serum α-fetoprotein level, vascular invasion, larger tumor, poor differentiation, and poor clinical outcome. The approved " stemness”-related markers included EpCAM, CD133, K19, and CD44, which often co-expressed and had their own characteristics. The presentation of " stemness”-related marker was heterogeneous and it increased the difficulty to carry on the research of therapeutic agents targeted against this aggressive HCC. Conclusion HCC expressing " stemness”-related marker is a special subtype with a strong invasiveness, which provides a new direction of targeting therapy for HCC.
ObjectiveTo investigate the expression change characteristic of stemness-related markers for recurrent hepatocellular carcinoma (HCC), and to discuss the relationship between stemness-related markers and clinicopathologic characteristics of HCC.MethodsWe collected 25 recurrent HCC patients who also had the first liver resection for HCC in Sichuan Cancer Hospital from Jan. 2010 to Oct. 2018. Immunohistochemistry was used to compare expressions of CD133, CD90, CD117, and epithelial cell adhesion molecule (EpCAM) in HCC tissues. Fluorescence in situ hybridization was used to detect telomere length.ResultsThe primary HCC had higher platelet count, larger tumor, less microvascular invasion (MVI), and less multiple HCC than the recurrent HCC (P<0.05), but the expressions of CD90, CD133, CD117, and EpCAM were not significantly differed after recurrence (P>0.05). The expressions of CD90, CD133, CD117, and EpCAM were not associated with tumor size, tumor number, Barcelona Clinic Liver Cancer Staging (BCLC staging), satellite nodules, and differentiation (P>0.05). The MVI-positive group had a significantly higher expression level of EpCAM (P=0.016) and longer telomere length (P=0.001). The telomere length was longer for tumors diameter less than 5 cm (P=0.038) and poor differentiation (P=0.046). Correlation analysis found that there was no relationship between telomere length and expression levels of EpCAM (r=–0.092, P=0.513), CD90 (r=–0.235, P=0.100), CD133 (r=0.024, P=0.867), and CD117 (r=–0.277, P=0.052), but an apparent positive correlation between expression levels of EpCAM and CD133 was found (r=0.358, P=0.011). Survival analysis found that poor differentiation (P=0.003) and BCLC B–C staging (P=0.040) were the risk factors of disease-free survival for patients after first HCC resection, and BCLC B–C staging (P=0.017) and tumor diameter more than 5 cm (P=0.035) were the risk factors for recurrent HCC.ConclusionsRecurrent HCC had similar stemness-related markers expression and longer telomere length. Expression level of EpCAM and telomere length were associated with MVI.
Objective To summarize the stemness regulation mechanism of microRNA on invasion, metastasis and chemoresistance of gastric cancer stem cells (GCSCs), and to explore the anti-tumor therapy based on miRNA targeting GCSCs. Method The literatures about the research progress of miRNA and GCSCs at home and abroad in recent years were collected and reviewed. Results MiRNA could regulate a series of important cellular processes such as proliferation, apoptosis, differentiation and epithelial-mesenchymal transition of GCSCs by participating in the expression of related target genes, which was associated with poor prognosis and high mortality of gastric cancer patients. Silencing or restoring the expression of candidate miRNA of GCSCs could provide a novel and promising approach for the treatment of gastric cancer. Conclusions GCSCs have an important relationship with the malignant biological behavior of gastric cancer, and studies have confirmed that miRNA play an important regulatory role in GCSCs. Therefore, miRNA can be used as a potential target for the treatment of gastric cancer. By regulating the expression of specific miRNA, it can inhibit tumor invasion and metastasis, and improve the sensitivity of chemotherapy drugs.
ObjectiveTo study the effect of Tangeretin on non-small cell lung cancer (NSCLC) and the tumor stemness, and to find the molecular mechanism of its effect. MethodsWe used cell counting and cell cloning experiments to study the effect of Tangeretin on the proliferation of NSCLC cells in vitro. The effect of Tangeretin on the invasion of NSCLC cells was detected by transwell assay. We detected the effect of Tangeretin on the proliferation of NSCLC cells in vivo by nude mouse tumor-bearing experiment. The effect of Tangeretin on tumor stemness of NSCLC cells was detected by self-renew assay, and CD133 and Nanog protein expressions. The expressions of PI3K/AKT/mTOR signaling pathway-related proteins were detected by Western blotting (WB). ResultsTangeretin had a good inhibitory effect on the proliferation of NSCLC cells in vivo and in vitro. Cell counting experiment, clonal formation experiment and nude mouse tumor-bearing experiment showed that Tangeretin could inhibit the proliferation activity, clonal formation ability, and tumor size of NSCLC cells in vivo. Self-renew experiments showed that Tangeretin could inhibit the self-renew ability of NSCLC cells. WB experiments showed that Tangeretin inhibited the expressions of tumor stemness markers CD133 and Nanog in NSCLC cells. Tangeretin could inhibit the activation of PI3K/AKT/mTOR signaling pathway-related proteins in NSCLC cells, and the activation of PI3K/AKT/mTOR signaling pathway could partially remit the inhibitory effect of Tangeretin on tumor stemness of NSCLC cells. ConclusionTangeretin can inhibit the tumor stemness of NSCLC cells, which may be related to the regulation of PI3K/AKT/mTOR signaling pathway.