Expression And Correlation Of EZH2 And SMYD3 In Colorectal Cancer Tissues

Background:Colorectal cancer?CRC?is a malignant tumor of the mucosal epithelium and glands in colon and rectum.With the improvement of living standards and lifestyle changes of Chinese residents,the incidence of colorectal cancer has remained high^[1].At present,the pathogenesis of colorectal cancer is still not completely clear,which makes it more difficult to treat colorectal cancer^[2],although the level of treatment such as surgery,chemotherapy,and targeted therapies continues to increase,the overall efficacy is still poor.In the process of diagnosis and treatment of colorectal cancer,TNM staging is usually an important basis for the clinical development of treatment programs and prognosis^[3],but the prognosis of patients with the same stage is very different,there is still a lack of effective early diagnosis and prognosis judgment methods.At present,the treatment methods are similar for most patients with the same disease condition.For example,the same drugs and standard doses are used,but the actual curative effects and adverse reactions are very different.The existence of these individual differences is mostly due to genetic polymorphisms.The EZH2?Enhancer of Zeste Hamologue 2?protein,the core component of the epigenetic regulatory factor PcG?Ploycomb Group?protein,is involved in cell growth regulation and is highly expressed in various malignancies.Studies abroad have found that^[5,6]EZH2 gene mediates tumor progression by enhancing histone H3K27 methylation,while SMYD3?Histone Methyltransferase 3?protein is a histone lysine methyltransferase that promotes chromosome Histone H3K4forms dimethylated or trimethylated,which promotes cell proliferation and metastasis.Its oncogenic effects have been confirmed in different malignant tumors.However,little is known about the expression and mechanism of EZH2 and SMYD3 proteins in colorectal cancer.Objectives:To detect the expression of EZH2 and SMYD3 protein in colorectal cancer tissues,analyze the expression of EZH2 and SMYD3 protein and their correlation with different pathological features and prognosis of colorectal cancer.To investigate the role of EZH2 and SMYD3 proteins in the development of colorectal cancer and to provide new molecular markers and targets for the diagnosis,treatment and prognosis of colorectal cancer.Materials and Methods:Colorectal cancer tissues?experimental group?and paracancer tissues?control group?were collected from paraffin-embedded specimens of patients undergoing radical resection of colorectal cancer at the Department of General Surgery,Affiliated Tumor Hospital of Zhengzhou University.Altogether 60 cases were included.Immunohistochemistry was used to detect the expression of EZH2 and SMYD3 protein in colorectal cancer tissues and adjacent tissues.Combining the postoperative pathology of patients with colorectal cancer,completed the TNM staging according to the 2017edition of the NCCN guidelines.The?2 test was used to analyze the expression differences of EZH2 and SMYD3 proteins in colorectal cancer tissues and adjacent tissues,The relationship between the expression of EZH2 and SMYD3 protein and pathological parameters of colorectal cancer.Kaplan-Meier method and Log-rank test were used to analyze the relationship between EZH2 and SMYD3 protein and disease-free survival?DFS?and overall survival?OS?after radical resection in patients with colorectal cancer.Pearson correlation was used to analyze the correlation of EZH2and SMYD3 protein expression in colorectal cancer tissues.Results:1.Among 60 cases of colorectal cancer,46 cases?76.67%?were positive for EZH2 protein,and 24 cases were positive?40.00%?in adjacent tissues?P=0.000<0.05?;In rectal cancer tissues,35 cases?58.33%?of SMYD3 protein were positive,and 21cases?35.00%?were positive in adjacent tissues?P=0.010<0.05?.2.In 31 cases of stage?and stage?colorectal cancer tissues,17 cases of EZH2 protein expression were positive,the expression rate was 54.83%.In 29 cases of stage?and stage?colorectal cancer tissues,28 cases of EZH2 protein were positive expression.The rate was 96.55%,and the difference was statistically significant?P=0.000<0.05?.In29 colorectal cancer tissues with lymph node metastases,26 were positive for EZH2protein expression,the expression rate was 89.66%,In 31 cases of colorectal cancer without lymph node metastasis,there were 20 cases of EZH2 protein positive expression,the expression rate was 64.52%?P=0.021<0.05?.There was no significant difference in the expression of EZH2 protein in age,gender,tumor location,differentiation degree and infiltration depth?P>0.05?.3.In 31 cases of stage?and stage?colorectal cancer tissues,173 cases of SMYD3protein expression were positive,the expression rate was 41.94%.In 29 cases of stage?and stage?colorectal cancer tissues,22 cases of SMYD3 protein were positive and expressed,The rate was 75.86%?P=0.008<0.05?.In 29 colorectal cancer tissues with lymph node metastasis,21 SMYD3 protein expression was positive,and the expression rate was 72.41%.In 31 colorectal cancer tissues without lymph node metastasis,14SMYD3 protein expression was positive,the expression rate was 45.16%?P=0.010<0.05?.In 28 cases of right colon cancer tissues,21 cases of SMYD3 protein expression was positive,the expression rate was 75.00%,while in 32 cases of left colorectal cancer tissue,14 cases of SMYD3 protein expression was positive,the expression rate was 43.75%?P=0.014<0.05?.There was no significant difference in the expression of SMYD3 protein in age,gender,differentiation degree and infiltration depth?P>0.05?.4.The 60 patients with colorectal cancer were followed up by telephone.Starting from the day of surgery,death,loss of follow-up,or cut-off time?September 1,2017?was the end point.A total of 56 follow-up data were obtained?93.33%?.The median postoperative DFS was 26.59 months in patients with EZH2 protein expression and 42.79 months in EZH2 protein negative patients?P=0.002<0.05?.The median postoperative DFS was24.49 months in patients with positive expression of SMYD3 protein,and the median postoperative DFS was 38.73 months in patients with negative SMYD3 protein expression?P=0.003<0.05?.There was no significant difference in postoperative median OS between EZH2 and SMYD3 protein positive patients and negative patients?P>0.05?.5.Among the 60 colorectal cancer tissues,31?51.67%?were EZH2 positive and SMYD3positive,15?25.00%?were EZH2 positive,SMYD3 negative,and 4?6.67%?EZH2negative.SMYD3 protein was positive,there were 10 cases?16.66%?EZH2 negative,SMYD3 protein negative,EZH2 and SMYD3 protein expression showed a positive correlation?r=0.333 P<0.05?.Conclusion:1.The positive rate of EZH2 and SMYD3 protein in colorectal cancer tissue was significantly higher than that in paracancer tissue,indicating that both of them are up-regulated in the development of colorectal cancer.2.The expression of EZH2 protein was significantly correlated with TNM stage and lymph node metastasis.The expression of SMYD3 protein was significantly correlated with TNM stage,lymph node metastasis and tumor site,indicating that the expression of both may be related to the invasion and metastasis of colorectal cancer.3.Patients with EZH2,SMYD3 protein positive colorectal cancer had a shorter postoperative DFS,suggesting that both two expression may indicate poor prognosis in patients with colorectal cancer.4.In colorectal cancer tissues,there was a positive correlation between the expression of EZH2 and SMYD3 proteins,indicating that they may have a synergistic effect in the development of colorectal cancer.