Expression And Clinical Significance Of CXCL17 And GPR35 In Endometrial Adenocarcinoma

Endometrial cancer(EC)is one of the most common gynecologic malignancies,and the most common histological type is endometrial adenocarcinoma.The number of women diagnosed with endometrioid adenocarcinoma is increasing every year.Although the prognosis is good,the annual mortality rate is still rising,accounting for 6 per cent of new cancer cases and 3 per cent of cancer deaths per year.Endometrial adenocarcinoma includes risk factors such as unfertility,early menarche,advanced menopause,age>55 years,ovarian disease(such as polycystic ovary syndrome),tamoxifen treatment,chronic liver disease and obesity.At present,endometrial adenocarcinoma lacks specific markers,and clinical diagnosis still depends on endometrial pathological biopsy.More and more attention has been paid to targeted therapy.Specific molecular markers can make diagnosis more accurate,but effective biomarkers remain to be determined,which is expected to become a new therapeutic target for guiding clinical practice.CXCL17 was first discovered in 2006 and was a CXC chemokine.According to its functional characteristics,CXCL17 was named as dendritic cells and monocyte chemoattractant protein(DMC)or vascular endothelial growth factor-related chemokine-1(VCC-1).It has the functions of recruiting immune cells,strong anti-inflammatory and antibacterial ability,chemotaxis,immune dynamic balance regulation,and tumor immune response.Some scholars have detected high levels of CXCL17 mRNA in type I endometrial adenocarcinoma,but there is no further study.Probably related to the development of endometrioid adenocarcinoma.G protein-coupled receptor type A(GPCR)was found more than 20 years ago and was newly named CXCR8(C-X-C motif chemokine receptor 8).It was identified as CXCL17 receptor,the expression of GPR35(CXCR8)is not only related to inflammation,but also related to gastric cancer,breast cancer,colon cancer and other tumors.Studies have shown that the expression of CXCL17 and its receptor GPR35 in liver cancer,breast cancer and colon cancer is higher than that in adjacent tissues,and its high expression is related to prognosis.However,the expression and role of CXCL17/GPR35 axis in endometrial adenocarcinoma need further study.ObjectiveAt present,the clinical significance of CXCL17 and GPR35 in endometrial adenocarcinoma is not clear.In this study,the expression of mRNA and protein levels of the two factors in endometrial adenocarcinoma was studied.The purpose of this study was to explore the expression of CXCL17/GPR35 in endometrial adenocarcinoma and its relationship with clinical pathological parameters,survival prognosis and immune infiltration,so as to provide new ideas for the treatment of endometrial adenocarcinoma.MethodsCollection of 35 pairs of paired endometrial carcinoma tissues and adjacent endometrial tissues in our hospital.Quantitative real-time polymerase chain reaction(QRT-PCR)was used to examine the mRNA expression levels of CXCL17 and GPR35.Tissue microarrays were used in 50 endometrial carcinoma tissues,30 atypical hyperplasia endometrial tissues and 110 normal hyperplasia endometrial tissues.Immunohistochemical staining(IHC)was performed to determine the expression of CXCL17 and GPR35 proteins in endometrial tissues of the three groups.The correlation between CXCL17 and GPR35 in endometrial carcinoma and clinical pathological characteristics was analyzed.Results1.mRNA expression of CXCL17 and GPR35 in endometrial tissueThe expression of CXCL17 mRNA in endometrial adenocarcinoma and adjacent tissues was(4.30±1.19)and(3.49±0.97),respectively.The expression levels of GPR35 mRNA in endometrial adenocarcinoma and adjacent tissues were(9.73±3.70)and(5.26±2.03),respectively.The expression levels of CXCL17 and GPR35 in endometrial adenocarcinoma were significantly higher than those in adjacent tissues,and the difference was statistically significant(CXCL17:P=0.019;GPR35:P=0.024).2.Protein expression of CXCL17 and GPR35 in different endometrial tissuesCXCL17 is mainly expressed in the cytoplasm of endometrial adenocarcinoma cells.GPR35 was expressed not only in the nucleus of endometrial adenocarcinoma tissue,but also in the cytoplasm.The positive expression rates of CXCL17 in normal proliferative phase,atypical hyperplasia and endometrial adenocarcinoma were 13.3%,63.3%and 72%,respectively.There was no significant difference in the positive rate between endometrial carcinoma and atypical hyperplasia tissues(P>0.05).But significantly higher than normal proliferative endometrium(P<0.001).The positive expression rates of GPR35 in normal proliferative phase,atypical hyperplasia and endometrial adenocarcinoma were 20.0%,66.7%and 70.0%,respectively.There was no significant difference in the positive rate between endometrial adenocarcinoma and atypical hyperplasia endometrial tissue(P>0.05).But significantly higher than normal proliferative endometrium(P<0.001).The expression of CXCL17 and GPR35 in endometrioid adenocarcinoma was higher than that in normal proliferative endometrium.3.Relationship between CXCL17 and GPR35 protein expression and clinicopathological features of endometrioid carcinomaThe positive expression of CXCL17 and GPR35 protein was not correlated with age,menopause,differentiation,depth of invasion,tumor diameter and lymph node metastasis in patients with endometrioid carcinoma(P>0.05).But it was significantly associated with clinicopathological stages(P<0.05).In addition,the expression of GPR35 was significantly correlated with the high proliferation rate of Ki-67(P=0.037).4.Correlation between CXCL17 and GPR35 expression in endometrial adenocarcinomaAccording to Pearson correlation analysis,the results showed that the expression of CXCL17 and GPR35 was highly correlated in endometrioid carcinoma.(r=0.9123,P<0.0001)Conclusion1.The expression of CXCL 17 and GPR35 mRNA in endometrioid carcinoma was significantly higher than that in adjacent tissues.There was no significant difference in the positive expression rate of CXCL 17 and GPR35 protein between endometrioid carcinoma and atypical endometrial hyperplasia.But significantly higher than normal proliferative endometrium.2.The positive expression of CXCL 17 and GPR35 protein was significantly correlated with the clinicopathological stage of patients with endometrioid carcinoma.The expression of CXCL 17 and GPR35 was highly correlated in endometrioid carcinoma.The overall survival(OS)of patients with high expression of CXCL 17 was significantly higher than that of patients with low expression of CXCL17,and GPR35 was not statistically significant.COX analysis showed that the expression of GPR35 was an independent prognostic factor for OS in patients with endometrioid carcinoma.