The Expression And Clinical Significance Of SOCS-1、NF-κB And COX-2in Colorectal Carcinoma

Objective: Colorectal carcinoma(CRC) is one of the common digestivetract malignant tumours. With the improvement of society, the morbidity andmortality of the colorectal carcinoma increased year by year, it does greatharm to human’s health.The pathogenetic mechanism of colorectal carcinomainvolving multiple elements,it includes oncogenes,tumor suppressor genes andmismatch repair genes.To study mechanisms of colorectal carcinoma hasgreat significance to clinical treatment.In the suppressor of cytokine signaling family, SOCS-1is a newtumour suppressor gene that had been in-depth studied. It could inhibit theproliferation of tumour cells and its abnormal expression was closely relatedto malignant tumor.SOCS-1can not only negatively regulate JAK/STAT signaltransduction pathway,but also could inhibit other signal pathways activated byvarious cytokines.So far,the study of SOCS-1on acute and chronicleukemias、 nephropathy、 gastric carcinoma、 liver cancer were moreconcentrated, but about colorectal rare. It was also found that there wasabnormal expression in colorectal tumors, suggesting that SOCS-1expressionmay be associated with tumor progression.NF-κB belongs to the family of Rel transcription factors,afteractivated it could take part in the formation of tumor，also control of theexpression of target genes，including COX-2. It is found that NF-κB wasclosely related to breast cancer, colon cancer, stomach cancer, liver cancer andso on. This shows, NF-κB could up-regulate the expression of COX-2, thecombination of the two mediated the occurrence and development of tumorCOX-2is an important rate-limiting enzyme of prostaglandin (PG)synthesis process.When cell had been stimulated, COX-2could quicklyexpressed,to participate in a variety of pathophysiological process. There are positive correlation between COX-2and pathogenetic, proliferation,differentiation, invasion, metastasis of tumour.In this experiment by detecting the expression of SOCS-1、NF-κB andCOX-2in colorectal carcinoma and normal colorectal tissue,this paperdiscussed the relationship between the SOCS-1、NF-κB and COX-2,anddiscussed the role of SOCS-1、NF-κB and COX-2played in the developmentof colorectal carcinoma.Methods: Selection45cases colorectal carcinoma tissues asexperimental group,25cases normal colorectal tissues as control group.Usingimmunohistochemical (SP) method、Western blot detected the expression ofSOCS-1、NF-κB and COX-2,and they were compressive analyzed accordingto the patient’ s sex，age，location，differentiation degree，lymph nodemetastasis and infiltration depth.SPSS13.0statistical data processing,countwith 2test, measurement data with t test,P＜0.05is statisticallysignificant.Using Spearman rank corrdlationg analysed the relationshipbetween SOCS-1、NF-κB and COX-2.Results:1. Immunohistochemical staining results1.1SOCS-1protein expressed in cytoplasm, positive expression wereyellow.The positive rate of SOCS-1in normal colorectal tissues was68%（17/25）,significantly higher than the positive rate in colorectal carcinoma24.4%（11/45）,the difference was significantly(P＜0.05).1.2NF-κB protein located in cytoplasm and nucleus，positive expression wasbrownish yellow. The positive rate of NF-κB in normal colorectal tissues was12%（3/25）, significantly lower than the positive rate in colorectal carcinoma64.4%（29/45）,there was a significant difference(P＜0.05).1.3COX-2protein located in nucleus, positive expression was brownishyellow. The positive rate of COX-2in normal colorectal tissues was16%（4/25）, significantly lower than the positive rate in colorectal carcinoma82.2%（37/45）, there was a significant difference(P＜0.05).2Western blot resultsWestern blot detected different levels of SOCS-1，NF-κB and COX-2protein expression in colorectal carcinoma and normal colorectal tissues. β-actin asthe internal protein,using LabWorks4.5protein bands analysis softwareanalysis all bands,we found that the protein relative strength of SOCS-1innormal colorectal tissues was（35.4694±8.04）,higher than the the proteinrelative strength in colorectal carcinoma, there was a significant difference(t=-11.926，P＜0.05）. In contrast,the relative expression intensity of NF-κBand COX-2were（23.8899±16.62）and（28.7915±10.23）,lower than thereexpression in colorectal carcinoma（68.0449±15.22）and（87.1742±17.94）,there were significant difference（t=-9.798，P＜0.05）、（t=-12.684，P＜0.05）.3The relationship among the expression of SOCS-1、NF-κB and COX-2incolorectal carcinoma and the clinicopathologic features of colorectalcarcinoma.The positive expression of SOCS-1in differentiated and well-differentiatedcolorectal carcinoma was56.25%（9/16）, significantly higher than the rate ofpoorly differentiated group6.9%（2/29）（P＜0.05）.The positive expression ofNF-κB among high-medium differentiation,not invading the serosa andwithout lymph node metastasis were31.3%（5/16）、31.6%(6/19)、26.7%(4/15),significantly lower than poorly differentiated,infiltrating serosa and withlymph node metastasis group82.8%（24/29）、84.6%(22/26)、80%(24/30),there were significant difference P＜0.05. The positive expression of COX-2among high-medium differentiation,not invading the serosa and withoutlymph node metastasis group were62.5%（10/16）、63.2%（12/19）、60%（9/15）,significantly lower than poorly differentiated,infiltrating serosa and withlymph node metastasis group93.1%（27/29）、96.2%（25/26）93.33%（28/30）,there were significant difference P＜0.05.The positive expression of SOCS-1had no significant relationship with patient’s sex,age,location and depth ofinvasion（P＞0.05）. The positive expression of NF-κB and COX-2had nosignificant relationship with patient’s sex,age and location（P＞0.05）.4The correlation among the expression of SOCS-1, NF-κB, COX-2incolorectal carcinoma.Using Spearman rank corrdlationg analysed the relationship between SOCS-1、NF-κB and COX-2,we found that SOCS-1and NF-κB protein incolorectal cancer was negative correlated (r=-0.376，P＜0.01), NF-κB andCOX-2was positively correlated (r=0.549，P＜0.01), SOCS-1and COX-2was negative correlated (r=-0.421，P＜0.01).Conclusions: The abnormal expression of SOCS-1, NF-κB and COX-2in colorectal carcinoma were very common.SOCS-1showed low expression incolorectal carcinoma, The positive expression of SOCS-1in differentiated andwell-differentiated colorectal carcinoma were significantly higher than the rateof poorly differentiated group.The positive expression of NF-κB andCOX-2among high-medium differentiation,not invading the serosa andwithout lymph node metastasis group were significantly lower than poorlydifferentiated,infiltrating serosa and with lymph node metastasis group.In thecolorectal carcinoma, SOCS-1and NF-κB was negative correlated, NF-kB andCOX-2was positively correlated,SOCS-1and COX-2was negativecorrelated.All of them play an important part in the occurrence and thedevelopment of colorectal carcinoma.