The Expression Of Chemokine CXCL5and Its Receptor CXCR2and Their Significance In Hepatocellular Carcinoma

Objective To detect the expression of C-X-C motif ligand5（CXCL5）, C-X-C motif receptor2（CXCR2）and microvessel density（MVD），analyze their mutual relationship, investigate their relationship between CXCL5,CXCR2and clinicopathologic features and the significance to the evaluation ofprognosis in hepatocellular carcinoma（HCC）. Methods ImmunohistochemicalEnvision method and real time fluorescence quantitative PCR（RT-qPCR）methodswere utilized to detect the expression of CXCL5and CXCR2, MVD andmicrolymphatic density（MLD）were marked by CD34and D2-40. The follow-up dataof the cases of HCC was analyzed by Kaplan-Merier method for survival with log-ranktest. Results In carcinoma and adjacent paraffin-embedded tissues of51cases ofHCC and30cases of frozen HCC carcinoma and adjacent tissues of them：（1）33casesoverexpressed the CXCL5protein in HCC, the high expression rate was64.7%, whichwas significantly higher than that in tumor-adjacent tissues （P<0.05）. Theoverexpression of CXCL5protein was statistically significant between different tumorsize, differentiation, TNM stage and with or without vascular invasion（P<0.05）, butwas not significant between different gender, age, alcohol intake history, HBsAg, HCV,AFP, GGT, tumor number and with or without liver cirrhosis（P＞0.05）. The quantityof CXCL5mRNA in carcinoma tissues was8.05±10.50, which was significantlyhigher than2.79±3.93in tumor-adjacent tissues（P<0.05）. The level of CXCL5mRNA had no significant difference between different gender, age, alcohol intakehistory, HBsAg, HCV, AFP, GGT, tumor number, TNM stage and with or without livercirrhosis, but was statistically significant between different tumor size, tumordifferentiation and with or without vascular invasion（P<0.05）（.2）Overexpression ofCXCR2protein was found in35cases of HCC, the high expression rate was significantly higher than those in tumor-adjacent tissues（68.6%vs15.7%）（P<0.05）.The overexpression of CXCR2protein was statistically significant between differenttumor grade and with or without vascular invasion（P<0.05）. The overexpression ofCXCR2protein between different gender, age, alcohol intake history, HBsAg, HCV,AFP, GGT, tumor number, tumor size, TNM stage and with or without liver cirrhosishad no significant difference（P＞0.05）. The level of CXCR2mRNA expression incarcinoma tissues and tumor-adjacent tissues was0.83±1.05,1.88±1.42respectively（P<0.05）. The level of CXCR2mRNA had no significant difference betweendifferent gender, age, alcohol intake history, HBsAg, HCV, AFP, GGT, tumor number,tumor size, tumor differentiation or TNM stage and with or without vascular invasionand liver cirrhosis（P＞0.05）.（3）The value of MVD was higher in HCC than that intumor-adjacent tissues （231.87±110.65vs146.08±64.68）（P<0.05）. The value ofMVD had no significant difference between different gender, age, alcohol intakehistory, HBsAg, HCV, AFP, GGT, tumor number, TNM stage and with or without livercirrhosis and vascular invasion, but was statistically significant between differenttumor size and tumor grade（P<0.05）. There was not microlymphatic staining whichmarked by D2-40in carcinoma nests, the value of MLD was0. The microlymphaticalmost distributed in stroma around carcinoma nest or near around liver blood sinus ofadjacent carcinoma.（4）By Spearman rank correlation analysis, the expression ofCXCL5protein and MVD had correlation（r=0.343，P=0.007）, as well as theexpression of CXCR2protein and MVD（r=0.267，P=0.029）; also as CXCL5andCXCR2protein（r=0.473，P＜0.001）in HCC.（5）By survival analysis of the44casesof HCC with follow-up data, the difference in terms of the rate of recurrence andmetastasis between the high and low expression of CXCL5and CXCR2protein wassignificant（P<0.05）, but had no difference in terms of the survival rate（P＞0.05）.The higher rate of recurrence and metastasis was in the group of higher expression ofCXCL5and CXCR2protein; It also showed significance difference in terms of the rateof recurrence and metastasis between the group of high and low value of MVD（P<0.05）, but had no difference in terms of the survival rate（P＞0.05）. Conclusions1. The expression of CXCL5and CXCR2protein and the mRNA levels of CXCL5in HCC tissues were higher than in tumor-adjacent tissues, and both of them wereassociated with the malignant degree of HCC, that suggust CXCL5and CXCR2maypromote the occurrence and development of HCC.2. The expression of CXCL5,CXCR2protein and MVD had correlation, it suggest CXCL5and CXCR2promote theneovasculation in HCC.3. The expression of CXCL5and CXCR2can be used as amarker to evaluate the prognosis of HCC.