Expression Of CYLD And IL-8 In Gastric Cancer And Precancerous Lesions

BACKGROUND:As one of the most common malignant tumors,gastric cancer(GC)has a high morbidity and mortality in China.Its precancerous lesion is gastric intraepithelial neoplasia(GIN),which can be divided into low-grade(LGIN)and high-grade intraepithelial neoplasia(HGIN),the risk of canceration increases with grade.CYLD(the cylindromatosis gene)encodes a deubiquitinase(DUB)that mediates reversible ubiquitination reactions and is widely involved in inflammatory responses,cell proliferation,differentiation and apoptosis.Recent studies have generally proved that CYLD plays an anti-cancer role in tumors and is related to the occurrence,development,metastasis and prognosis of tumors.Interleukin-8(IL-8)is an inflammatory chemokine with various biological functions,which can chemotactic inflammatory cells,induce cell proliferation,etc.It is produced by paracrine and autocrine pathways in tumor tissues,affecting tumor microenvironment,promoting angiogenesis and metastasis,even participating in the mechanism of tumor recurrence and drug resistance.CYLD and IL-8 may play a role in the pathogenesis of gastric cancer.Exploring and understanding the molecular mechanism of the occurrence and development of gastric cancer can provide theoretical basis for diagnosis and treatment.OBJECTIVE:To detect the expression of CYLD and IL-8 in GC and GIN,and to explore the correlation between them.METHODS:From January 1,2017 to May 31,2018,87 cases of newly diagnosed and resected gastric adenocarcinoma and 87 cases of paracancerous normal tissues were selected from Department of Gastroenterology or General Surgery,Huaihe Hospital,Henan University.During the same period,52 cases of intraepithelial neoplasia were confirmed pathologically by gastric mucosal biopsy,including 24 cases of low-grade intraepithelial neoplasia and 28 cases of high-grade intraepithelial neoplasia.Immunohistochemistry(S-P)was used to detect the expression of CYLD and IL-8 in gastric cancer,adjacent normal tissues,low-grade and high-grade gastric intraepithelial neoplasia.The correlation between the expression in gastric adenocarcinoma and clinicopathological data(age,sex,tumor size,depth of invasion,lymph node metastasis,clinical TNM staging,CEA value and Ki-67 index)was analyzed,also the correlation between CYLD and IL-8.RESULTS:1.The positive expression rates of CYLD in gastric adenocarcinoma group,paracancerous tissues group,high grade intraepithelial neoplasia(HGIN)group and low grade intraepithelial neoplasia(LGIN)group were:paracancerous(80.5%)>LGIN(62.5%)>HGIN(53.6%)>gastric adenocarcinoma(32.2%).There were significant differences between the four groups(?~2=41.729,P<0.001).Chi-square segmentation tests showed:the expression of CYLD in gastric adenocarcinoma was significantly different from that in the paracancerous normal tissues(?~2=41.211,P<0.001)and that in LGIN(?~2=7.285,P=0.007),but the difference was not statistically significant compared with that in HGIN(?~2=4.139,P=0.042).The expression of CYLD in paracarcinoma normal tissues was different from that in HGIN(?~2=7.943,P=0.005),but not significantly different from that in LGIN(?~2=3.383,P=0.066).However,there was no difference between HGIN and LGIN(?~2=0.422,P=0.516).Further analysis of the relationship between the expression of CYLD in gastric adenocarcinoma and various clinicopathological indicators,showed that there were no difference among age,sex,CEA value and tumor diameter,but there were differences among different invasion depth,lymph node metastasis,clinical TNM stage and Ki-67 index:T1-T2 stage of tumor invasion,CSCO stage I-II,no lymph node metastasis and low Ki-67 index with low expression,T3-T4 stage of tumor invasion,advanced gastric cancer(CSCO stage III-IV),lymph node metastasis and high Ki-67 index with lower expression,the differences were statistically significant(P<0.05).2.The positive expression rates of IL-8 in gastric adenocarcinoma group,paracancerous tissues group,high grade intraepithelial neoplasia(HGIN)group and low grade intraepithelial neoplasia(LGIN)group were:gastric adenocarcinoma(64.4%)>HGIN(50%)>LGIN(41.7%)>paracancerous(12.6%).There were significant differences between the four groups(?~2=49.732,P<0.001).Chi-square segmentation tests showed:the expression of IL-8 in paracarcinoma normal tissues was significantly different from that in gastric adenocarcinoma(?~2=49.149,P<0.001),HGIN tissues(?~2=17.375,P<0.001),and LGIN tissues(?~2=10.329,P=0.001).In addition,the expression of IL-8 in gastric adenocarcinoma was not significantly different from that in HGIN(?~2=1.836,P=0.175),LGIN(?~2=4.022,P=0.045),or between HGIN and LGIN(?~2=0.361,P=0.548).Then the relationship between the expression of IL-8 in gastric adenocarcinoma and various clinicopathological indicators were analyzed,the results showed no difference among age,gender,tumor diameter;but there were differences among different depth of invasion,lymph node metastasis,clinical TNM staging,CEA value and the Ki-67 index:T1-T2 stage of tumor invasion,CSCO stage I-II,no lymph node metastasis,low CEA value and low Ki-67 index with high expression,T3-T4 stage of tumor invasion,advanced gastric cancer(CSCO stage III-IV),lymph node metastasis,high CEA value and high Ki-67 index with higher expression,as opposed to CYLD,the differences were statistically significant(P<0.05).3.Correlation analysis showed a negative correlation between CYLD and IL-8 expression in gastric adenocarcinoma(?~2=8.330,r=-0.309,P=0.004).CONCLUSION:1.CYLD plays an inhibitory role in the occurrence and development of gastric cancer.2.IL-8 promotes the occurrence,development and metastasis of gastric cancer.3.Inhibition of CYLD may promote the production of IL-8 and the progression of gastric cancer.