The Expressions And Significance Of Oct4 And TGF-β/BMP Signaling Pathway In The Occurrence And Development Of Gastric Carcinoma And The Relationship Among Them

Objective:To discuss the Oct4, Smad1 and Smad2 expressions in gastric cancer and normal gastric tissue and the interactions of them. Analyze test data of Oct4, Smad1 and Smad2 protein and m RNA to discover the potential relationship among Oct4, Smad1 and Smad2. It might provide a new mentality for the pathogenesis of gastric cancer, as well as provide potential drug targets for gastric cancer.Methods:We has collected 60 cases of the gastric cancer and 25 cases of normal gastric tissues that10 cm away from cancer edge in Chengde Medical College Affiliated Hospital from July 2011 to December 2013, all cases has been confirmed by postoperative pathological examination, there were no cancer adjacent to carcinoma tissue. Use Immunohistochemistry detection and Western blotting technology to test Oct4, Smad1 and Smad2 protein expression,apply QReal- Time PCR technique to detect Oct4, Smad1 and Smad2 m RNA expression. And then we combine the experimental data with clinical pathology data to carry out statistical analysis. We use the Person correlation analysis of measurement data, with P<0.05 for the difference had statistically significant.Results:1. Results of Immunohistochemistry1.1 Protein expression of Oct4, Smad1 and Smad2 in gastric normal and cancer tissuesIn gastric cancer tissues expression of Oct4 was obviously higher than that of normal gastric tissue(P<0.05), expression of Smad1 and Smad2 in gastric cancer tissue is obviously lower than that in normal gastric tissue(P<0.05).1.2 The relationship between the protein expression of Oct4, Smad1 and Smad2 with the pathological features of patientsThe protein expression of Oct4, Smad1 and Smad2 with gender and age have no statistical significance, the results between male and female, > 56 years old and ≤56 years old both had no difference.Oct4 protein expression in high-middle differentiation gastric cancer tissue is lower than poor differentiated group(P<0.05), Smad1 and Smad2 protein expression in high-middle differentiation gastric cancer tissue is higher than poor differentiated group(P<0.05).In Ⅰ&Ⅱ period of TNM staging in gastric cancer Oct4 protein is less positive than Ⅲ&Ⅳ period(P<0.05), In Ⅰ&Ⅱ period of TNM staging in gastric cancer Smad1 and Smad2 protein is more positive than Ⅲ&Ⅳ period(P<0.05).In gastric cancer tissue with no serous invasion Oct4 protein expression is lower than with serous invasion(P<0.05), In gastric cancer tissue with no serous invasion Smad1 and Smad2 protein expression is higher than the tissue with serous invasion(P<0.05).In gastric cancer with no lymph node metastasis expression of Oct4 protein is lower than the tissue with lymph node metastasis(P<0.05), in gastric cancer with no lymph node metastasis expression of Smad1 and Smad2 protein is higher than the tissue with lymph node metastasis(P<0.05).2. Results of Western Blotting2.1 Protein expression of Oct4, Smad1 and Smad2 in gastric normal and cancer tissuesIn gastric cancer tissues expression of oct4 was obviously higher than that of normal gastric tissue(P<0.05), expression of Smad1 and Smad2 in gastric cancer tissue is obviously lower than that in normal gastric tissue(P<0.05).2.2 The relationship between the protein expression of Oct4, Smad1 and Smad2 with the pathological features of patientsThe protein expression of Oct4, Smad1 and Smad2 with gender and age have no statistical significance, the results between male and female, > 56 years old and ≤56 years old both had no difference.Oct4 protein expression in high-middle differentiation gastric cancer tissue is lower than poor differentiated group(P<0.05), Smad1 and Smad2 protein expression in high-middle differentiation gastric cancer tissue is higher than poor differentiated group(P<0.05).In Ⅰ&Ⅱ period of TNM staging in gastric cancer Oct4 protein is less positive than Ⅲ&Ⅳ period(P<0.05), In Ⅰ&Ⅱ period of TNM staging in gastric cancer Smad1 and Smad2 protein is more positive than Ⅲ&Ⅳ period(P<0.05).In gastric cancer tissue with no serous invasion Oct4 protein expression is poorer than with serous invasion(P<0.05), In gastric cancer tissue with no serous invasion Smad1 and Smad2 protein expression is higher than the tissue with serous invasion(P<0.05).In gastric cancer with no lymph node metastasis expression of Oct4 protein is lower than the tissue with lymph node metastasis(P<0.05), in gastric cancer with no lymph node metastasis expression of Smad1 and Smad2 protein is higher than the tissue with lymph node metastasis(P<0.05).3. Results of QReal-Time PCR3.1 The m RNA expression of Oct4, Smad1 and Smad2 in gastric normal and cancer tissuesIn gastric cancer tissues expression of oct4 was obviously higher than that of normal gastric tissue(P<0.05), expression of Smad1 and Smad2 in gastric cancer tissue is obviously lower than that in normal gastric tissue(P<0.05).3.2 The relationship between the m RNA expression of Oct4, Smad1 and Smad2 with the pathological features of patientsThe m RNA expression of Oct4, Smad1 and Smad2 with gender and age have no statistical significance, the results between male and female, > 56 years old and ≤56 years old both had no difference.Oct4 m RNA expression in high-middle differentiation gastric cancer tissue is lower than poor differentiated group(P<0.05), Smad1 and Smad2 m RNA expression in high-middle differentiation gastric cancer tissue is higher than poor differentiated group(P<0.05).In Ⅰ&Ⅱ period of TNM staging in gastric cancer Oct4 m RNA is less positive than Ⅲ&Ⅳ period(P<0.05), In Ⅰ&Ⅱ period of TNM staging in gastric cancer Smad1 and Smad2 m RNA is more positive than Ⅲ&Ⅳ period(P<0.05).In gastric cancer tissue with no serous invasion Oct4 m RNA expression is lower than with serous invasion(P<0.05), In gastric cancer tissue with no serous invasion Smad1 and Smad2 m RNA expression is higher than the tissue with serous invasion(P<0.05).In gastric cancer with no lymph node metastasis expression of Oct4 m RNA is lower than the tissue with lymph node metastasis(P<0.05), in gastric cancer with no lymph node metastasis expression of Smad1 and Smad2 m RNA is higher than the tissue with lymph node metastasis(P<0.05).4. Correlation analysis of Oct4, Smad1 and Smad2Correlation analysis of Immune histochemical data: Oct4 correlated negatively with Smad1: r =-0.882(P<0.05); Oct4 correlated negatively with Smad2: r =-0.859(P<0.05); Smad1 correlated positively with Smad2: r =0.905(P<0.05).Correlation analysis of Western Blotting data: Oct4 correlated negatively with Smad1: r =-0.769(P<0.05); Oct4 correlated negatively with Smad2: r =-0.812(P<0.05); Smad1 correlated positively with Smad2: r = 0.911(P<0.05).Correlation analysis of QReal Time-PCR data: Oct4 correlated negatively with Smad1: r =-0.892(P<0.05); Oct4 correlated negatively with Smad2: r=-0.909(P<0.05); Smad1 correlated positively with Smad2: r=0.778(P<0.05).Conclusion:1. Smad1 and Smad2 are components of TGF-β/BMP signaling pathway, and have synergistic effect on the incidence of gastric cancer cells’ biology process. They synergistic lead to abnormal changes of TGF-β/BMP signaling pathway, thus promote the occurrence, development and metastasis of gastric cancer.2. Oct4 negatively related Smad1 and Smad2 which are components of TGF-β/BMP signaling pathway, therefore, inhibiting Oct4 overexpression can inhibit the occurrence development, invasion and metastasis of gastric cancer, which provides a new train of thought for potential drug targets of stomach cancer targeted therapy.3. Oct4 is an important regulatory factor to TGF-β/BMP signaling pathway.