The Combined Detection Of CDX2，COX-2and NF-κB/P65in Gastric Carcinoma And Their Clinical Significance

BackgroundGastric Cancer, as a common malignant gastrointestinal cancer, has a high incidence inChina. Due to the latent onset, this disease is difficult to be detected in early stage and isoften diagnosed at advanced stage, most of cancers appear serosal invasion, lymph nodemetastasis even distant organ metastasis and lose the best opportunity for surgicaltreatment. Although the practices according to multimodality therapy philosophy (suchas chemotherapies before and after surgery) extend the patient’s survival, the effect isstill not satisfactory. Therefore, early diagnosis, early assessment and treatment hasimportant clinical significance for the prognosis of gastric cancer.Caudal-type homeobox transcription factor2(CDX2) belongs to homeobox gene family,and acts as a key transcription factor in the maintenance and differentiation of thecharacteristics of intestinal epithelial cells; in addition to its control action in theembryonic development and differentiation, it also controls adult tissue differentiationand proliferation. Cyclooxygenase-2(COX-2), as a key enzyme for inflammationinitiation, can catalyze the arachidonic acid to be converted into thromboxane A2andprostaglandin; this enzyme, as a induced expression gene, is almost undetectable innormal tissue, but it can be rapidly synthesized under the actions of growth factors,cancer-promoting agents and inflammatory cytokines. Nuclear transcription factorκB/P65(NF-κB/P65), a widespread cell nuclear transcription factor, can regulate thetranscription ability of many genes in tumors so as to regulate tumor cell proliferationand apoptosis. Researches in recent years suggested that CDX2, COX-2and NF-κB/P65were abnormally expressed in a variety of tumors, moreover, they were associated totumorigenesis, progression and migration and other biological behaviors and can beused for tumor diagnosis and prognosis prediction, some studies also proposed that these three as the targets for cancer prevention. Therefore, by analyzing the positiveexpression rates of gastric CDX2, COX-2and NF-κB/P65as well as their relevancewith the clinical pathological features and follow-up data, this paper aims to provide areference value for the diagnosis and prognosis prediction of gastric cancer, and toclarify their important theoretical significance and clinical value.ObjectiveThis paper aims to explore the expressions of CDX2, COX-2and NF-κB/P65in gastrictissue, so as to analyze the relevance between their expressions and common clinicaland pathological features&follow-up data.Methods1.42cases of patients admitted into this hospital from Jan.,2008to Dec.,2008underwent surgeries and were postoperatively and pathologically diagnosed as gastriccancer. Their paraffin--embedded samples (including adjacent tissues) were collected,and all these patients had a complete clinical, pathological and follow-up data, in thesame period, the healthy gastric mucosa of20cases confirmed by gastroscope biopsywere also collected as control.2. The two-step immunohistochemical SP method was used for the staining of CDX2,COX-2and NF-κB/P65in gastric cancer tissues, corresponding adjacent tissues andnormal gastric tissues; the duplex scoring method combing staining intensity andpositive cells was used to identify the positive and negative staining expression ofstaining, and to analyze the expressions in different tissues.3. The relevance among different expression levels of CDX2, COX-2and NF-κB/P65ingastric cancer with the common clinicopathological parameters (include age, gender,Lauren’s histological type, histological grade, tumor diameter, tumor location, depth ofinvasion, lymph node metastasis and TNM staging), and the prognosis were analyzed.Results1. In the gastric cancer tissues, adjacent tissues and normal tissues, the high expression rates of CDX2were57.14%,78.57%and10.00%respectively, the positive rates ofCOX-2were61.90%,7.14%and0%respectively, the positive rates of NF-κB/P65were71.43%,19.05%and30.00%respectively; the positive rate of COX-2in adjacenttissues was significantly higher than that in the gastric cancer tissues and normal tissues,and that in the gastric cancer tissues was higher than that in normal tissues (P <0.05);the positive rates of COX-2and NF-κB/P65were higher than those in adjacent tissuesand normal tissues (P <0.05), and the differences between adjacent tissues and normaltissues were not statistically significant (P>0.05).2. The distributions of positive expression of CDX2in different Lauren’s histologicaltypes, histological grades, tumor diameters, depths of invasion, lymph node metastasisand TNM staging were statistically significant (P <0.05), but the distributions of that indifferent ages, genders and tumor locations were not statistically significant (P>0.05);the distributions of positive expression of COX-2in different histological grades, tumordiameters, depths of invasion, lymph node metastasis and TNM staging werestatistically significant (P <0.05), but the distributions of that in different ages, genders,Lauren’s histological types and tumor locations were not statistically significant (P>0.05); the distributions of positive expression of NF-κB/P65in different lymph nodemetastasis and TNM staging were statistically significant (P <0.05), but the distributionsof that in different ages, genders, Lauren’s histological types, histological grades, tumordiameters, depths of invasion and tumor locations were not statistically significant (P>0.05).3. The expression of CDX2was negatively correlated with that of COX-2(r=0.672, P=0.041); the expression of CDX2was negatively correlated with that of NF-κB/P65(r=-0.335, P=0.030); while the expression of COX-2was positively correlated with thatof NF-κB/P65(r=0.372, P=0.015).4. The Kaplan-Meier survival curve showed that the patients with positive expression ofCDX2had higher survival rate compared with the patients with negative expression of CDX2, and the patients with high expressions of COX-2and NF-κB/P65had lowersurvival rate than the patients with low expressions of COX-2and NF-κB/P65. Theresults of Log Rank test showed that the differences were statistically significant (P<0.05).Conclusion1. The expressions of CDX2, COX-2and NF-κB/P65have distribution differences ingastric cancer tissues, the positive expression rates of COX-2and NF-κB/P65in gastriccancer tissues are higher than those in adjacent tissues, while the positive expressionrates of CDX2is lower than that in adjacent tissues.2. All of those three indicators are related with the clinicopathological features of gastriccancer, but the relevance among those three indicators and a specific clinicopathologicalfeature were not identical; in addition, the expression of CDX2was negativelycorrelated with that of both COX-2and NF-κB/P65, and the expression of COX-2waspositively correlated with that of NF-κB/P65, those suggest that they may work jointlyin the occurrence and development of gastric cancer.3. The expression levels of CDX2, COX-2and NF-κB/P65are related with survival rate,the patients with positive CDX2, negative COX-2and NF-κB/P65have significantlyhigher survival rates compared with the patients with negative CDX2, positive COX-2and NF-κB/P65, which suggests that the joint detection of those three indicators ishelpful for prediction of prognosis.