| Objective: Primary liver cancer is one of the most common malignanttumors in China. The annual number of deaths due to primary liver cancer isabout0.11million, which accounts for roughly45%of the death toll of livercancer worldwide. Primary liver cancer is highly malignant and of rapidprogression, from having clinical symptoms to death, usually covering4to6months, sometimes even1to2months, and hepatocellular carcinomaaccounts for90%of this disease. Currently, comprehensive treatment ofsurgical excision is the most effective method towards hepatocellularcarcinoma. However, the5-year recurrence rate of hepatocellular carcinomapatients after radical resection is up to61.5%, and even for smallhepatocellular carcinoma, the recurrence rate after5years is up to43.5%,which becomes the problem of the clinical treatment of hepatocellularcarcinoma. If metastasis and recurrence of hepatocellular carcinoma can notbe solved, the postoperative long-term efficacy will be difficult to enhance,thus affecting the entire hepatocellular carcinoma prognosis. With thedevelopment of molecular biology techniques and the deepening of thetumor-related research, it was discovered that there exists a class of tumorcells with stem cell characteristics in many tumors, namely cancer stem cells.The cancer stem cells are closely related to tumor growth, development,recurrence and metastasis. The present study showed that cancer stem cellshave the self-renewal, unlimited proliferation and multilineage differentiationability. Although cancer stem cells in tumor tissue account for only a verysmall proportion, they play a decisive role in the tumorigenesis process. Dueto the fact that most of these tumor stem cells are in a quiescent state, they canescape the killing of radiotherapy and chemotherapy. The proposal of thecancer stem cell concept for the treatment of the tumor provides a new direction. The research on some core regulatory factors of maintaining stemcells' self-renewal and proliferation mechanism in tumor is an important partof the cancer stem cell research. OCT4, SOX2and NANOG are now publiclyrecognized as the stem cell regulatory factors, and play an important role inthe maintenance of stem cells' self-renewal, proliferation and multi-directionaldifferentiation potential. Nowadays there have been many reports on therelationship between OCT4, SOX2, NANOG and such cancers as gastriccancer, colon cancer, breast cancer, pancreatic cancer, glioma, bladder cancer,and so on. However, there has been little report concerning their relationshipto hepatocellular carcinoma(HCC). In this research, according to the detectionof OCT4, SOX2and NANOG in hepatocellular carcinoma tissue,paracancerous tissue and normal liver tissue, we analyzed the expressionlevels of OCT4, SOX2and NANOG in hepatocellular carcinoma, studied theirrealtionship with the patients' clinical pathological features, and explored therole and clinical significance of OCT4, SOX2and NANOG in the occurrenceand development of hepatocellular carcinoma.Methods: The tissue samples collected were surgical resectionspecimens of the Hepatobiliary Surgery of the Fourth Hospital of HebeiMedical University from March2010to December2011, with50cases ofhepatocellular carcinoma specimens,44cases of paracancerous tissuespecimens and14cases of normal liver tissue specimens. We detected theexpression levels of the stem cell transcription factors OCT4, SOX2andNANOG in terms of protein and nucleic acid in cancerous tissue,paracancerous tissue and normal liver tissue by immunohistochemistrystaining (SP method) and RT-PCR respectively. The obtained data wereanalyzed with SPSS13.0statistical software for statistical analysis, usingchi-square test, t-test and spearman grade analysis methods to study theirrealtionship with Liver cancer clinical and biological characteristics and theirmutual relations.Results:1OCT4, SOX2and NANOG were all expressed in HCC tissue and paracancerous tissue, with almost no expression in normal liver tissue. In HCCtissue, paracancerous tissue and normal liver tissue, the positive expressionrates of OCT4protein were76%(38/50),54.5%(24/44) and7.1%(1/14)respectively, and the expression levels of OCT4mRNA were1.002士0.180,0.807士0.187and0.029士0.007respectively; In HCC tissue, paracanceroustissue and normal liver tissue, the positive expression rates of SOX2proteinwere62.0%(31/50),40.9%(18/44) and0%(0/14) respectively, and theexpression levels of SOX2mRNA were0.283士0.075,0.181士0.036and0.022士0.002respectively; In HCC tissue, paracancerous tissue and normalliver tissue, the positive expression rates of NANOG protein were82%(41/50),63.6%(28/44) and0%(0/14) respectively, and the expressionlevels of NANOG mRNA were0.410士0.148,0.291士0.07and0.026士0.007respectively. The expression levels of OCT4, SOX2and NANOG inHCC tissue were significantly higher than those in paracancerous tissue andnormal liver tissue.(P<0.05).2In HCC tissue, the positive expression rates of OCT4, SOX2, andNANOG protein were90.0%(27/30),80.0%(24/30) and96.7%(29/30)respectively for the TNM stage (III-IV) patients with hepatocellular carcinoma,and the expression levels of OCT4, SOX2, and NANOG mRNA were1.106士0.123,0.327士0.049and0.489士0.124respectively; the positiveexpression rates of OCT4, SOX2, and NANOG protein were55.0%(11/20),35.0%(7/20) and60.0%(12/20) respectively for the TNM stage (I-II) patientswith hepatocellular carcinoma, and the expression levels of OCT4, SOX2, andNANOG mRNA were0.813士0.083,0.201士0.02and0.270士0.051respectively.The expression levels of OCT4, SOX2, and NANOG for theTNM stage (III-IV) patients with hepatocellular carcinoma were significantlyhigher than those for the TNM stage (I-II) patients.(P<0.05).The positiveexpression rates of OCT4, SOX2and NANOG protein in poorly differentiatedcarcinoma group (III, IV level) were92.6%(25/27),85.2%(23/27) and100%(27/27) respectively, and the expression levels of OCT4, SOX2, andNANOG mRNA were1.177士0.079,0.359士0.021and0.544士0.112 respectively; The positive expression rates of OCT4, SOX2and NANOGprotein in well-differentiated carcinoma group (I,II level) were56.5%(13/23),34.8%(8/23) and60.9%(14/23) respectively, and the expressionlevels of OCT4, SOX2, and NANOG mRNA were0.870士0.104,0.230士0.043and0.306士0.064respectively.The expression levels of OCT4, SOX2,and NANOG in poorly differentiated carcinoma group (III, IV level) weresignificantly higher than those in well-differentiated carcinoma group (I,IIlevel)(P<0.05). The expression levels of OCT4, SOX2and NANOG wereunrelated to the patients' gender, age and tumor size (P>0.05).Immunohistochemistry and RT-PCR experiments were consistent in theresults.3In HCC tissue, the expression levels of OCT4and SOX2, SOX2andNANOG, OCT4and NANOG all had positive correlation (P<0.05).Conclusion:1The expression levels of stem cell transcriptional regulatory factorsOCT4, SOX2and NANOG in HCC tissue were all significantly higher thanthose in paracancerous tissue and normal liver tissue, indicating that OCT4,SOX2, NANOG are closely related to the occurance and development ofhepatocellular carcinoma.2The expression levels of OCT4, SOX2, NANOG were closely relatedto the clinical stage and degree of tumor differentiation of patients withhepatocellular carcinoma, but had nothing to do with factors such as age,gender, tumor size, and so on, indicating that OCT4, SOX2, NANOG arerelated to the biological characteristics of HCC.3In HCC tissue, the expression levels of OCT4and SOX2, SOX2andNANOG, OCT4and NANOG all have positive correlation, indicating that inhepatocellular carcinoma there may be have interactions and linkages amongOCT4, SOX2and NANOG to jointly promote the occurance and developmentof hepatocellular carcinoma.4In hepatocellular carcinoma combined detection of OCT4, SOX2andNANOG can accurately reflect the biological characteristics of HCC. |
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