The Expression And Significance Of KLF9 In Esophageal Carcinoma And Dysplasia Of Esophagus

ObjectivesEsophageal cancer is is one of the most common malignant tumors in the world, which is a serious threat to human health. The occurrence of esophageal cancer is generally through dysplasia, carcinoma in situ, invasive cancer and metastasis. All patients of esophageal cancer had insidious onset, and they had not any symptom in early stages. When the symptoms are obvious, most of patients were in the middle or the late stages. At present, the patients of dysplasia and carcinoma in situ can be completely cured.The treatment effect of early cancer is good, and the prognosis of early cancer is better than other stages. But the treatment of patients with advanced esophageal cancer is very limited. When the disease is discovered, most of the patients were not suitable for surgery, and the 5 year survival rate is less than 20%. Therefore, the early diagnosis of esophageal cancer is very important. KLF9 is thought to be an important tumor suppressor gene,and it plays an inhibition role during the course of tumors. The objective of the present study is to investigate the expression of KLF9 gene in protein and mRNA levels in human esophageal carcinoma and dysplasia,to explore the role of KLF9 in the development of esophageal carcinoma and the value of the gene expression detection in discovery of patients with high cancer risk and the early diagnosis of esophageal cancer. Materials and methods1. specimen source 40 cases of fresh specimen were collected from september 2014 to march 2015 in the second affiliated hospital of zhengzhou university, including 20 cases of esophageal carcinoma and 20 normal esophageal(away at least from the tumor edge 3cm). Put the fresh sample in the-80°C refrigerator quickly. 90 cases of wax block were collected in the pathology archive of the second affiliated hospital of zhengzhou university, including 30 cases of esophageal carcinoma, 30 cases of dysplasia and 30 cases of normal esophageal tissues. All specimens were confirmed by pathology, and the patients had not got any radiotherapy, chemotherapy and biological therapy, immune therapy and biological chemical toxicity. All the patients had complete clinical and pathological data. The ATM stageing is according to the seventh edition of esophageal cancer TNM staging of AJCC and UICC.2. Methods Immuno histochemical method was used to detect the expression of KLF9 protein in esophageal cancer tissues, dysplasia tissues and normal esophageal tissues.Fluorescence quantitative PCR(RTQ-PCR) method was used to detect the expression of KLF9 mRNA in esophageal cancer tissues and normal esophageal tissues.3. Statistics processing Statistical analysis was performed with SPSS 17 software. Scores of immuno histochemistry were refered to the IRS score method. The difference of the expression of KLF9 in normal esophageal tissue, dysplasia tissue and esophageal cancer tissues was analyzed by fourfold table c2 test. The difference between positive expression of esophageal carcinoma and its clinical parameters was analyzed by fourfold table c2 test fisher exact probability method. △△Ct method were used to compare the difference of the expression of KLF9 mRNA between esophageal carcinoma tissues and normal esophageal tissues. Results1. The positive expression rate of KLF9 in normal esophageal tissue, dysplasia and esophageal carcinoma were 90%(27 / 30), 80%(32 / 40), 45%(18 / 40), and it showed a gradual downward trend. Compared with normal esophageal tissue, the expression of dysplasia tissues was significantly decreased(p=0.002). Compared with normal esophageal tissue, the expression of esophageal cancer tissues was significantly decreased(P<0.001). The positive expression of KLF9 protein in esophageal cancer was not significantly related to the sex, age, location, histological type, lymph node metastasis of the patients(P > 0.05). But it was significantly related to the the depth of tumor invasion, tumor differentiation and tumor size(P < 0.05).2.We calculated the relative expression level of KLF9 mRNA using 2-△△ct method,and it showed the level of mRNA KLF9 in esophageal dysplasia was significantly lower than that in normal esophageal tissue, and the difference was statistically significant(P < 0.01). Conclusions1.The expression of KLF9 was decreased in protein and mRNA level in esophageal cancer tissues which sugected that the abnormal expression of the KLF9 was closely related to the occurrence of esophageal cancer.2.The expression of KLF9 in esophageal cancer was downregulated, and the dysplasia with decreased expression of KLF9 may be more likely to have malignant potensial.3.The expression of KLF9 in esophageal carcinoma was related to the size,differentiation degree and depth of invasion of esophageal cancer, which suggested that abnormal expression of KLF9 was related to the malignant progression of esophageal cancer.