The Expression Of TSLP In Epithelial Ovarian Cancer And Its Clinical Prognostic Analysis

Ovarian cancer is a common genital tumor which threatens women's health.Because of the difficulties of early diagnosis,patients with ovarian cancers often have poor prognosis.Although the pathogenesis of ovarian cancer remains unclear,people have made great progress in clinical pathology with the help of using molecular biology as a research tool.Because ovarian cancer lacks effective prognostic and diagnostic indicators,the corresponding molecular biomarkers are urgently needed to be discovered.Thymic stromal lymphopoietin(TSLP)is an IL-7-like cytokine originally identified in the culture supernatant of mouse thymic stromal cell lines,which initially thought to be a lymphocyte growth factor.Researchers later discovered that TSLP is a key factor in linking the balance of interfaces between body and environment(skin,airways,gut,ocular tissue,etc.)to Th2 cell responses.Recent studies have shown that TSLP plays a role in the development of malignant tumors,including Hodgkin's disease,pancreatic cancer,cervical cancer,breast cancer,and gastric cancer.Ovarian cancer has been considered to be a malignant tumor with a dominant Th2 cell response.Considering the role of TSLP in maintaining the barrier Th2 homeostasis such as mucosa and in al ergic diseases and some malignant tumors which Th2-type responses predominate,we speculate TSLP may be involved in the development of ovarian cancer and may be a biomarker of ovarian cancer or even a therapeutic target.This study aims to explore the value of TSLP as a potential molecular biomarker in the diagnosis and prognosis of ovarian cancer and provide a new method for the early diagnosis of ovarian cancer,and further explore the role of TSLP in mechanism of the development in ovarian cancer and whether it can be a potential therapeutic target for ovarian cancer.Objective: The objective of this study is to evaluate the relationship between the expression of TSLP in epithelial ovarian cancer cell lines and ovarian cancer tissues,and that of the expression of TSLP and the clinicopathological parameters of ovarian cancer cases and the prognosis of ovarian cancer patients.Further,it also includes that to determine the value of TSLP in diagnosis and prognosis epithelial ovarian cancer and to pave the way for further clinical transformation and basic research on the corresponding mechanisms of the pathogenesis and development of ovarian cancer.Methods: 1.We cultured human EOC cell lines SKOV3,HO8910 and immortalized ovarian epithelial cell line IOSE386,then extracted RNA from cel s of three cell lines and reverse-transcribed into c DNA and detected the m RNA expression level of TSLP of three cell line cel s by real-time quantitative PCR.We also used enzyme linked immunosorbent assay to detect the level of TSLP in cell culture supernatant of three cell lines.2.We collected cancer tissue and adjacent normal tissue samples from 27 patients with ovarian cancer affiliated to Nanjing Maternal and Child Health Hospital affiliated to Nanjing Medical University and extracted RNA and reverse-transcribed into c DNA.Real-time quantitative PCR was used to detect m RNA expression level of TSLP in ovarian cancer tissue and adjacent normal tissues.3.We collected 144 patients with primary epithelial ovarian cancer with different histological types,25 ones with ovarian benign tumors,38 ones with ovarian borderline tumors,25 ones with normal ovaries,29 ones with fal opian tubes and 38 ones with endometrial cancer having done attachment resection from the hospital affiliated to Nantong University as subjects,and their clinicopathological parameters were recorded in detail.Immunohistochemical tissue microarrays were prepared using all of the above patients' tissues to detect the expression of TSLP in these patient's tissues and to analyze the relationship between TSLP expression and the patient's clinicopathological parameters and prognosis.Results:1.The expression of TSLP m RNA and protein in the two human epithelial ovarian cancer cell lines SKOV3 and HO8910 was significantly higher than that in the immortalized ovarian epithelial cell line IOSE386(P<0.01),the expression of TSLP m RNA and protein in the two human epithelial ovarian cancer cell lines was significantly different from the immortalized ovarian epithelial cell lines.2.Compared with malignant tumors,the high expression of TSLP was significantly different between normal ovaries,normal fal opian tubes,benign tumors,borderline tumors,and malignant tumors(P<0.01),and TSLP was highly expressed in malignant tumors.3.High expression of TSLP in epithelial ovarian cancer was significantly associated with age at diagnosis(P = 0.009),histological type(P = 0.022),FIGO stage(P < 0.001),degree of tissue differentiation(P = 0.015),pelvic involvement(P < 0.001)and the presence or absence of lymph node metastasis(P = 0.034).No other significant association was observed between TSLP high expression and other clinicopathological features.4.Kaplan-Meier survival curves for overall survival and disease-free survival showed significantly shorter overall survival and disease-free survival in patients with high TSLP expression compared with patients in the low TSLP expression group.P values were less than 0.001,and the differences were statistically significant.By log-rank test for univariate analysis,we found that TSLP expression,age at diagnosis,FIGO stage,degree of tissue differentiation,presence or absence of pelvic metastases,and presence or absence of lymph node metastasis were significantly associated with prognosis in patients with epithelial ovarian cancer(P < 0.05).By multivariate Cox proportional hazard model analysis,we found that high expression of TSLP and pelvic involvement were independent predictors of prognosis in patients with epithelial ovarian cancer.Conclusion: 1.TSLP has high expression in epithelial ovarian cancer cel s and tissues 2.High expression of TSLP is significantly associated with some clinicopathological parameters of epithelial ovarian cancer.3.High expression of TSLP and pelvic involvement are independent predictors of prognosis in patients with epithelial ovarian cancer.4.In conclusion,TSLP might be a potential biomarker for the diagnosis and prognosis of epithelial ovarian cancer and a therapeutic target for epithelial ovarian cancer.