Expression And Correlation Of PPARγ And ERRα In Endometrial Carcinoma

Objective: Detection The expression of peroxisome proliferator-activated receptors γ(PPAR γ)and estrogen related receptor α(ERR α)in endometrial cancer(EC).The correlation between PPAR γ,ERR α and clinical prognosis of endometrial cancer was analyzed.To explore whether PPAR γ/ERR α was an independent risk factor for endometrial cancer.This study focus on the relationship between PPAR γ and ERR α in endometrial cancer and the role of this relationship in the development of endometrial cancer.Methods: 77 cases of endometrial cancer confirmed by surgical pathology were collected from the Fujian Provincial Maternal and Child Health Hospital as a case study group.Fractional curettage or endometrial biopsy were performed for other benign gynecological diseases.39 cases of tissue specimens confirmed as normal endometrium were used as control group.Clinical informations such as age,maternal parity,body mass index(BMI),serum biochemical index,and serum tumor index were collected.The expression of mRNA of PPAR γ and ERR α were detected by Q-PCR,and the expression of protein of PPAR γ and ERR α were detected by immunohistochemistry.Correlation between expression of PPAR γ and ERR α was analyzed by Spearman rank correlation analysis.The relationship between PPAR γ and ERR α was explored by Sting protein interaction,and the target genes common to PPAR γ and ERR α were predicted by CistromeMap database.The biological functions of the target genes shared by PPAR γ and ERR α were analyzed by Go enrichment,and the pathways in which PPAR γ and ERR α were explored by Kegg enrichment analysis.Results: 1.Compared with normal endometrium,the expression of PPAR γ mRNA in endometrial cancer was(0.3128±0.0904),P=0.001.There was no statistically significant difference in PPAR γ mRNA between stages.However,immunohistochemistry showed that II-IV endometrial cancer had a lower positive rate of PPAR γ than stage I endometrial cancer.The expression of ERR α mRNA was(5.3710±2.1330)compared with normal endometrium,P < 0.001.There was no statistically significant difference in ERR α mRNA between stages,consistent with immunohistochemistry results.2.The lower the degree of differentiation of endometrial cancer,the higher the expression of PPAR γ mRNA.However,the difference was not statistically significant.Immunohistochemistry showed that the higher the degree of differentiation of endometrial cancer,the lower the positive rate of PPAR γ,the difference was statistically significant(P=0.014).The expression of ERR α mRNA was not significantly correlated with the degree of differentiation of endometrial carcinoma,which was consistent with immunohistochemistry.3.Compared with type I endometrial cancer,the expression of PPAR γ mRNA in type II endometrial cancer was 0.3534±0.0745(P=0.014),which was consistent with the results of immunohistochemistry.PPAR γ was highly expressed in ER and PR positive endometrial cancer.Compared with type I endometrial cancer,the expression of type II endometrial cancer ERR α mRNA was 0.3495 ± 0.1205(P = 0.064),consistented with immunohistochemistry.ERR α mRNA was highly expressed in endometrial cancer with ER and PR positive.4.The expression of PPAR γ was negatively correlated with that of ERR α.The ratio of PPAR γ/ERR α was analyzed by ROC curve.The threshold of PPAR γ/ERR α was 1.86.AUC was 0.915.Youden index was 0.6633.Sensitivity was 74.03%.and Specificity was 92.31%.The probability of developing endometrial cancer was higher when PPAR γ/ERR α≤1.86.Logistic regression analysis found that PPAR γ/ERR α<1.86 population had a higher risk of endometrial cancer than PPAR γ/ERR α≥1.86 population(OR=33.024,95%CI:2.794-390.32,P=0.006).PPAR γ immunohistochemically positive compared with PPAR γ immunohistochemical negative patients with low risk of endometrial cancer(OR=0.044,95% CI: 0.003-0.582),ERR α immunohistochemical positive compared to ERR α immunohistochemistry Negative patients have a high risk of developing endometrial cancer(OR=7.441,95% CI: 1.331-41.61).5.The disease-free survival rate of PPAR γ-negative patients was lower than that of PPAR γ-positive patients(P=0.001).The disease-free survival rate of ERR α-positive patients was lower than that of ERR α-negative endometrial cancer.Hoever the difference was not statistically significant(P=0.472).The disease-free survival rate of PPAR γ-negative ERR α-positive patients was significantly lower than that of PPAR γ-positive ERR α-positive and PPAR γ-positive ERR α-negative patients(P=0.005).Conclusion: The expression of PPAR γ was lower in endometrial cancer than that in normal endometrium.On the contrary,The expression of ERR α was higher in endometrial cancer than that in normal endometrium.There was a negative correlation between the expression of PPAR γ and ERR α.PPAR γ/ERR α may be a sensitive indicator for the diagnosis of endometrial cancer.PPAR γ and ERR α were therapeutic targets for endometrial cancer,which were expected to be important means and effective way for the treatment of endometrial cancer.