| Objective:In recent years,the incidence of laryngeal cancer is increasing,it is a common malignant tumor in otolaryngology head and neck surgery.the mortality rate accounts for about 0.75% of malignant tumors.More than 95%is a squamous cell carcinoma(SCC),which is the most common pathological type in laryngeal malignant tumor.As well as other malignant tumors,the occurrence and development of laryngeal cancer involves multiple factors,and the process is very complicated.The regulation disorder of the cell cycle is closely related to the occurrence of tumor.Cell cycle protein(cyclin),cyclin dependent kinase(CDK)and cyclin dependent kinase inhibitors(CKI)are the three large molecules in the regulation of cell cycle,CKIs negatively regulates cell cycle.p27 as one members of the cyclin dependent kinase inhibitor family,mainly inhibits the activity of cyclin/CDK,which leads to the failure of the cell cycle through the G1/S restriction and the termination of the cell cycle.Bmi-1 can up-regulate the expression of cyclin D1 and downregulate the expression of p27 in the nucleus via PTEN-AKT-GSK3? signal pathway,which promotes the cell cycle to cross the restriction point of G1/S,and accelerate the process of cell division.Sal like gene-4(SALL4)can activate the classic Wnt signal transduction pathway,this pathway can induce transcription and translation of its downstream target gene c-myc,the C terminal of c-myc can combine with Max to form c-myc/Max,which can bind to the promoter sequence of p27 to inhibit the transcription and expression of p27,which leds to the cell cycle regulation disorder.This study used the immunohistochemical method to mainly detecte the expression of SALL4,Bmi-1 and p27 in laryngeal squamous cell carcinoma(LSCC)and clarify the role of the three protein in the process oflaryngeal carcinogenesis and development,and analyze the correlation of the three proteins.We try to explore the carcinogenesis,invasion and metastasis mechanism of laryngeal carcinoma and provide reliable basis and clues for laryngeal cancer molecularly targeted therapy.Methods:1 We selected 51 cases of LSCC tissue as experimental group and 21 cases of adjacent normal tissues as control group,which were undergone surgical treatment and confirmed by postoperative pathology from the department of Otolaryngology Head and neck surger in fourth hospital of Hebei Medical University from March 2015 to October 2016.we used immunohistochemistry(IHC)(S-P method)to evaluate the expression of Bmi-1,SALL4,and p27 in the two groups and to further analyze the correlation of the three in LSCC.2 The experimental data were analyzed by using statistical software SPSS21.0,P<0.05 indicating statistical differences.Results:1 The expression of SALL4The positive expression of SALL4 mainly concentrated in the nucleus,showed brown yellow or brown granules in the nucleus,but also a small amount of cytoplasm appeared pale yellow or brown.The positive expression rate of SALL4 in LSCC and adjacent tissues were 64.7% and 47.6%,respectively,the expression rate of SALL4 in the former was significantly higher than that in the latter,and the difference was statistically significant(P<0.05).The positive expression rate of SALL4 was closely related with the clinical stage in LSCC,the SALL4 positive expression in I + II stage laryngeal carcinoma group was 53.3%,and was 81% in III + IV stage laryngeal carcinoma group,the SALL4 positive expression rate in the latter was significantly higher than that in the former,the later clinical stage,the positive expression of SALL4 was higher(P<0.05).The SALL4 expression was closely related with differentiation in laryngeal carcinoma,the positiveexpression rate of SALL4 in well differentiated,moderately differentiated,poorly differentiated carcinoma tissues were 33.3%,70.8%,80%,respectively,with the higher degree of malignancy of laryngeal carcinoma,the positive expression of SALL4 level also increased gradually(P<0.05).The positive expression rate of SALL4 in the group with lymph node metastasis(84.2%)was higher than that without lymph node metastasis(53.1%),and the two groups expression rates were statistically significant(P<0.05).The positive expression of SALL4 in laryngeal carcinoma was not correlated with age,sex,amount of smoking,tumor size and clinical classification(P>0.05).2 The expression of Bmi-1The positive expression of Bmi-1 mainly concentrated in the nucleus,showed brown yellow or brown granules in the nucleus,but also a small amount of cytoplasm appeared brown.The positive expression rate of Bmi-1in LSCC group(66.7%)was significantly higher than that in the adjacent tissue group(9.5%),the difference of the two groups had statistical significance(P<0.05).The positive expression rate of Bmi-1 in III + IV stage case(87.5%)was significantly higher than that in I+II stage case(58.6%),the Bmi-1 positive expression rate was closely related with the clinical stage in LSCC(P<0.05).The Bmi-1 positive expression rates in well differentiated,moderately differentiated,poorly differentiated carcinoma tissues were 33.3%,75% and80%,respectively,the expression of Bmi-1 was gradually increased with the decrease of the differentiation degree of laryngeal carcinoma(P<0.05).The Bmi-1 expression was closely correlated with lymph node metastasis,and the positive expression rate in lymph node metastasis group was higher than that without lymph node metastasis group(84.2% vs,56.3%,P<0.05).The Bmi-1expression was not significantly correlated with age,sex,amount of smoking,tumor size and clinical classification in laryngeal carcinoma(P>0.05).3 The expression of p27The positive expression of p27 mainly concentrated in the nucleus,showed brown yellow or brown granules in the nucleus.The p27 positiveexpression rates in LSCC and adjacent tissues were 47.1% and 71.4%,respectively.The difference between the two groups was statistically significant(P<0.05).The p27 expression was closely related with the tumor differentiation in laryngeal carcinoma,the p27 positive expression in well differentiated,moderately differentiated,poorly differentiated carcinoma tissues were 66.7%,45.8%,13.3%,respectively,the difference was statistically significant(P<0.05).The positive expression rate of p27 in the group with lymph node metastasis and the group without lymph node metastasis were 31.6% and65.6%,respectively,the difference between the two groups was statistically significant(P<0.05).The positive expression rate of p27 in I+II stage case40% and was 57.1% in III + IV stage case,but there was no statistical significance(P>0.05).The p27 expression in laryngeal carcinoma was not significantly correlated with age,sex,amount of smoking,tumor size and clinical classification(P>0.05)4 Relationships of SALL4,Bmi-1 and p27It showed that the expression of SALL4,Bmi-1 and p27 in LSCC was correlated with each other by analyzing the experimental data.There was a positive relationship between the expression of Bmi-1and SALL4 in LSCC(r=0.383,P=0.006),there was a negative relationship between the expression of Bmi-1 and p27 in LSCC(r=-0.374,P=0.007).there was a negative relationship between the expression of p27 and SALL4 in LSCC(r=-0.314,P=0.025).Conclusion:1 The SALL4 protein was expressed in LSCC tissues and adjacent normal tissues,but the expression level of SALL4 in laryngeal carcinoma group was higher than that in the adjacent normal tissues,which suggested that SALL4 may be closely related to the occurrence of laryngeal carcinoma.2 The positive expression of SALL4 and Bmi-1 protein in LSCC was correlated with tumor differentiation,clinical stage and lymph node metastasis,which suggested that both proteins may be closely related to the occurrence,development,invasion and metastasis of LSCC.3 In LSCC,there was a positive correlation between the expression of Bmi-1 and SALL4,there was a negative correlation between the expression of p27 and SALL4,there was a negative correlation between the expression of Bmi-1 and p27.4 Detecting the expression of SALL4,Bmi-1 and p27 protein may help to understand the relationship and role of the three in the development of laryngeal carcinoma and provide theoretical basis about molecular targeted therapy for laryngeal cancer. |
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