The Correlations Among EZH2 Expression, MMP-28 Expression And EGFR Mutation And Clinical Significance In Lung Adenocarcinoma

Background and objectivesWith the aggravation of environmental pollution, the incidence of lung cancer is increasing year by year, which has become a serious threat to human health. More than 80% of lung cancer is non small cell carcinoma, the main part of which is adenocarcinoma.In recent years, the targeted drugs(EGFR-TKIs, etc) for lung adenocarcinoma has achieved good effect, but the drug comes into being resistance near furthure, then the efficacy decreased.EZH2 belongs to Pc G family, a histone lysine methyltransferase, which may affect the expression of tumor related genes by histone methylation. EZH2 plays a key role in tumorigenesis, invasion and metastasis.MMPs, a kind of proteolytic enzymes, plays an important role in tumor invasion and metastasis by disintegrating the extracellular matrix and promoting the formation of tumor blood vessels. MMP-28 is the newest member of MMPs family, and its research is very few. The role of EZH2 and MMP-28 in lung adenocarcinoma is not really clear, and the study of their relationships with EGFR mutation has not yet been reported.In this study, we detect EGFR mutation by real-time fluorescence PCR and tested the expressions of EZH2 and MMP-28 with Immunohistochemistry. Furthermore, the relationships among EZH2 expression and MMP-28 expression and EGFR mutation were investigated in order to provide a theoretical basis for finding more effective remedy and reducing patients EGFR-TKIs resistance.Methods50 surgical resections of lung adenocarcinoma were collected in the second hospital of Jilin University. All specimens were detected EGFR mutation by real-time fluorescence PCR, and examined the expression of EZH2 and MMP-28 with Immunohistochemistry in normal lung tissues, lung benign lesions and lung adenocarcinoma. Then we investigate the relationships among expression of EZH2 and MMP-28 and EGFR mutation, and analysis clinical significance.Results1. The most common locations of the EGFR mutation were in exon 19 and 21.2. The expression of EZH2 in lung adenocarcinom significantly greater than that in normal lung tissues and benign lung disease(P<0.05). The expression of EZH2 had no significant difference between the normal lung tissue and lung benign lesion tissues(P>0.05).EZH2 expression was significantly different among different histological subtypes of adenocarcinoma(P=0.007). The expression of EZH2 in adherent type was significantly lower than that in the acinar type and solid type(P=0.014; P=0.009), the expression of EZH2 had no significant difference between acinar type and solid type(P>0.05), the expression of EZH2 had no statistical significance in other subtypes(P> 0.05). EZH2 expression was related with tumor size and T stage. With the increase of tumor size and T stage, the positive rate of EZH2 expression was higher. EZH2 express was not associated with the lymph node metastasis, gender and age(P>0.05).3. The expression of MMP-28 in lung adenocarcinom significantly greater than that in normal lung tissues and benign lung disease(P<0.05). The expression of MMP-28 had no significant difference between the normal lung tissue and lung benign lesion tissues(P>0.05).MMP-28 expression was significantly different among different histological subtypes of adenocarcinoma(P=0.015). The expression of MMP-28 in adherent type was significantly lower than that in the acinar type and solid type(P=0.023; P=0.009), the expression of MMP-28 had no significant difference between acinar type and solid type(P>0.05), the expression of MMP-28 had no statistical significance in other subtypes(P>0.05). MMP-28 expression was related with tumor size, T stage and lymph node metastasis. With the increase of tumor size and T stage, the positive rate of MMP-28 expression was higher. MMP-28 express was not associated with the gender and age(P>0.05).4. The expression of EZH2 and MMP-28 were not associated with TTF-1 expression(P>0.05). The expression of EZH2 and MMP-28 were not associated with EGFR mutation(P>0.05).5. TTF-1 expression was positively correlated with EGFR mutation(P<0.05).6. MMP-28 expression was positively correlated with EZH2 expression(P<0.05).Conclusions1. EZH2 and MMP-28 may involve in lung oncogenesis and development. It is likely to be a new target for the treatment of lung adenocarcinoma.2. The expression of EZH2 and MMP-28 were not associated with TTF-1 expression and EGFR mutation.3. There was synergized effect between EZH2 and MMP-28 in the occurrence and development of lung adenocarcinoma. We speculated that EZH2 promotes the invasion of tumor by upregulated MMP-28.