The Study Of The Relationship Between FoxO3a As Well As FoxP4 And Colorectal Carcinoma’s Occurrence And Development

Objectives To detect the expressions of FoxO3 a and FoxP4 as well as four mismatch repair proteins(MLH1、PMS2、MSH2、MSH6)in the colorectal carcinoma tissues and it’s sideward intestinal mucosal tissues without tumor,and through the joint detection of KRAS,NRAS,BRAF,PIK3CA(referred as the genes detection of KNBP)four genes type states in some colorectal cancer patients,and explore FoxO3 a and FoxP4’s expressions as well as their internal correlational relationships.Furthermore,detecting the expression of four MMR proteins with USA Roche automatic immunohistochemist,to study the relationships of their expressions and clinicopathological features as well as the absence of mismatch repair protein expression,to analysis the relationships between KRAS gene mutation and the two factors expressions as well as clinicopathological features.Methods The clinicopathological data of 1025 patients who had received radical resection of colorectal carcinoma,during 2019.1 to 2021.12 in the Nroth China University of Science and Technology’s attched hospital—Tangshan Gong Ren Hospital,were screened out from all postoperative immunohistochemistry results as a total of 48 patients with mismatch repair protein expression loss,three of the inline KNBP genetic testers were excluded,and the remaining 45 cases were selected as the dMMR /MSI-H group,the remaining 977 patients with complete mismatch repair protein expression were randomly selected as a total of 45 patients named p MMR/MSS group.Besides,as a total of 42 patients who agreed to undergo joint testing of KNBP genes in colorectal cancer were collected,due to the hightest mutation rate was KRAS gene,which made us study the relationship between KRAS gene status and clinicopathogical characteristics as well as the expressions of the two antibodies,which named KRAS group.The number of 132 cases above,including the wax blocks of postoperative cancer tissues and their sideward intestinal mucosal tissues without tumor,were collected,by using immunohistochemistry En Vsion two-step method to detect the expressions of the two antibodies in all wax blocks by of immunohistochemical staining.Meanwhile,using ARMS-PCR method to detect 42 patients undergoing genetic testin.The clinicopathology data and experimental data of 132 patients to sort out and analyzed timely.Results 1 dMMR/MSI-H group,the positive rates of FoxO3 a and FoxP4 in colorectal cancer were 26.7% and 84.4% as well as in paracellular carcinomatous intestinal mucosal tissues were 86.7% and 11.1%.p MMR/MSS group,the positive rates of FoxO3 a and FoxP4 in colorectal cancer tissues were 31.1% and 80.0%,and in the paracous intestinal mucosal tissue were 84.4% and 20.0%.KRAS group,the positive rates of FoxO3 a and FoxP4 in colorectal tumors were 28.6% and 85.7%,and in the paracous carcinomatous intestinal mucosal tissue were 90.5% and 9.5%.The data above all have statistically significance(p=0.000).2 In 132 cases,FoxO3 a positive rate was 28.8% and FoxP4 positive rate was 83.3%,the expression of them in colorectal cancer showed a weak negative correlation(r=-0.299,p=0.000).3 In the dMMR/MSI-H group and p MMR/MSS group respectively,the expression of FoxO3 a in colorectal cancer tissues was both related to clinical stage(p=0.015,p=0.010)and presence or absence of lymph node metastases(p=0.023,p=0.023),which both not associated with sex(p=0.685,p=0.920)、age(p=0.982,p=0.173)、tumor site(p=0.356,p=1.000)、maximum tumor diameter(p=0.339,p=0.763)、 histological type(p=0.308,p=0.295)、 degree of differentiation(p=0.561,p=1.000)、 depth of infiltration(p=0.651,p=0.637)and distant metastases(p=1.000,p=1.000);The expression of FoxP4 in colorectal cancer tissues was related to clinical stage(p=0.016,p=0.014)and presence or absence of lymph node metastases(p=0.031,p=0.031),which both not related to sex(p=0.847,p=0.941)、age(p=0.115,p=1.000)、 tumor site(p=0.240,p=1.000)、 maximum tumor diameter(p=0.087,p=0.331)、histological type(p= 0.468,p=0.934)、degree of differentiation(p=1.000,p=1.000),depth of infiltration(p=0.613,p=0.939)and distant metastases(p=0.156,p=0.569).In colorectal cancer tissues,there were no significant differences between dMMR/MSI-H group and p MMR/MSS group in FoxO3 a positive rates(p=0.642)and FoxP4 positive rates(p=0.581).4 The results of genes test of KNBP showed that 21 cases had KRAS gene mutations with exon 2 mutations,NRAS and BRAF and PIK3 CA gene mutations were 0.KRAS gene mutations were related with FoxO3a’s expression in colorectal cancer tissues(p=0.017),the presence or absence of mucosal adenocarcinoma(p=0.005),and the exist of distant metastasis(p=0.049),which not associated with sex(p=0.217)、age(p=0.533)、tumor site(p=0.352)、maximum tumor diameter(p=0.217)、degree of differentiation(p=1.000)、 depth of infiltration(p=0.872)、 lymph node metastasis(p=1.000)and the expression of FoxP4(p=0.186).Conclusions 1 Decreased FoxO3 a expression and elevated FoxP4 expression play a catalytic role in the development of colorectal caicinoma,and the two are negatively correlated.2 The expression of FoxO3 a and FoxP4 in colorectal cancer was associated with clinical staging and lymph node metastasis,and was not associated with the absence or existence of mismatch repair proteins.3 The mutation rate of the KRAS gene in colorectal cancer tissues was high in patients with tubular adenocarcinoma,distant metastases,and FoxO3a-negative expression,independent of FoxP4 expression.Figure 6;Table 8;Reference 136...