孕激素治疗子宫内膜不典型增生症患者的有效性与TRIM22表达的相关性临床研究

Correlation between the effectiveness of progestogen therapy and TRIM22 expression in endometrial atypical hyperplasia

目的 探究孕激素治疗子宫内膜不典型增生症(AEH)患者的有效性及其与TRIM22表达的相关性。方法 (1)回顾性收集并分析本院收治的86例AEH患者的病历资料及病理组织。患者的治疗方案为口服醋酸甲羟孕酮250 mg,qd,或醋酸甲地孕酮160 mg,qd,疗程3个月。根据患者的病理组织结果分为治疗有效组(59例)和治疗无效组(27例)。用免疫组化法检测患者病理组织。(2)将子宫内膜Ishikawa细胞分为Ishikawa-空白组、Ishikawa-对照组和Ishikawa-低、中、高剂量实验组。Ishikawa-空白组培养基中不加药,Ishikawa-对照组加入50%的乙醇,Ishikawa-低、中、高剂量实验组分别加入20,40,80μmol·L^(-1)的醋酸甲羟孕酮溶液。将子宫内膜KLE细胞分为KLE-空白组,KLE-对照组和KLE-低、中、高剂量实验组。KLE-空白组培养基中不加药,KLE-对照组加入50%乙醇,KLE-低、中、高剂量实验组分别加入20,40,80μmol·L^(-1)的醋酸甲羟孕酮溶液。用细胞计数试剂盒-8法检测子宫内膜癌细胞增殖能力;用Transwell法检测细胞侵袭能力;用流式细胞术检测细胞凋亡情况。结果 (1)孕激素治疗有效组治疗后与治疗前比较,AEH患者子宫内膜组织中TRIM22表达显著增加,差异有统计学意义(P<0.05)。(2)子宫内膜癌细胞系KLE中空白组、对照组和低、中、高剂量实验组的细胞增殖能力分别为(2.00±0.15)%,(1.30±0.12)%,(1.96±0.11)%,(1.74±0.13)%和(1.82±0.17)%;细胞侵袭个数分别为159.35±16.32,98.01±11.25,169.14±18.74,149.18±11.32和127.93±14.23;细胞凋亡能力分别为(11.13±1.13)%,(30.72±1.43)%,(15.90±1.30)%,(20.95±2.53)%和(24.74±2.11)%。KLE-低、中、高剂量实验组与KLE-对照组的细胞增殖能力相比差异显著,差异有统计学意义(P<0.05)。子宫内膜癌细胞系Ishikawa中空白组、对照组和低、中、高剂量实验组的细胞增殖能力分别为(1.51±0.10)%,(1.23±0.16)%,(1.50±0.19)%,(1.39±0.24)%和(0.95±0.11)%;细胞侵袭个数分别为149.13±15.89,100.27±15.34,168.58±28.01,137.39±21.01和112.15±10.02;细胞凋亡能力分别为(10.47±1.19)%,(29.57±1.01)%,(18.94±1.04)%,(26.73±1.06)%和(40.46±1.25)%。Ishikawa-中、高剂量实验组与Ishikawa-低剂量实验组相比,差异均有统计学意义(均P<0.05)。结论 孕激素治疗AEH的有效性与TRIM22表达升高相关。

Objective To investigate the effectiveness of progestin treatment for atypical endometrial hyperplasia(AEH) and its correlation with TRIM22 expression. Methods(1)The medical records and pathological tissues of 86 patients with AEH our hospital were retrospectively collected and analyzed. Patients were treated with an oral medroxyprogesterone acetate 250 mg,qd,or medroxyprogesterone acetate 160 mg,qd,for 3months. According to their pathological tissue results,the patients were divided into a treatment effective group( 59patients) and a treatment ineffective group( 27 patients). The patients ’ pathological tissues were examined by immunohistochemistry.(2)The endometrial Ishikawa cells were divided into Ishikawa-blank,Ishikawa-control and Ishikawa-L,-M,-H groups. No drug was added to the medium of the Ishikawa-blank group;50% ethanol was added to the Ishikawa-control group;20,40,80 μmol·L-1of medroxyprogesterone acetate solution was added to the Ishikawa-L,-M,-H groups,respectively. The endometrial KLE cells were divided into Ishikawa-blank,KLE-control,KLE-L,-M,and-H groups. No drug was added to the medium of the KLE-blank group,50% ethanol was added to the KLE-control group,and 20,40,80 μmol·L^(-1)of medroxyprogesterone acetate solution was added to the KLE-L,-M and-H groups,respectively. The proliferation ability of endometrial cancer cells was detected by the cell counting kit-8 method;the invasion ability of cells was detected by the Transwell method,and the apoptosis of cells was detected by flow cytometry. Results(1)The expression of TRIM22 in endometrial tissues of AEH patients was significantly increased after treatment in the effective group of progestin therapy compared with that before treatment,and the difference was statistically significant( P < 0. 05).(2)The cell proliferation capacity of the KLE-blank,KLE-control,KLE-L,-M and-H groups were( 2. 00 ± 0. 15) %,( 1. 30 ± 0. 12) %,( 1. 96 ± 0. 11) %,( 1. 74 ± 0. 13) % and( 1. 82 ± 0. 17) %, respectively;the number of cells invaded were 159. 35 ± 16. 32,98. 01 ± 11. 25,169. 14 ± 18. 74,149. 18 ± 11. 32 and 127. 93 ± 14. 23, respectively;apoptotic capacity were( 11. 13 ± 1. 13) %,( 30. 72 ± 1. 43) %,( 15. 90 ± 1. 30) %,( 20. 95 ± 2. 53) % and( 24. 74 ± 2. 11) %,respectively. The difference in cell proliferation capacity between the KLE-L,-M,-H and the KLE-control group was significant( P < 0. 05). The cell proliferation capacity of the Ishikawa-blank,Ishikawa-control,and Ishikawa-L,-M and-H groups were( 1. 51 ± 0. 10) %,( 1. 23 ± 0. 16) %,( 1. 50 ± 0. 19) %,( 1. 39 ± 0. 24) % and( 0. 95 ±0. 11) %,respectively;the number of cells invaded were 149. 13 ± 15. 89,100. 27 ± 15. 34,168. 58 ±28. 01,137. 39 ± 21. 01 and 112. 15 ± 10. 02,respectively;apoptotic capacity were( 10. 47 ± 1. 19) %,( 29. 57 ± 1. 01) %,( 18. 94 ± 1. 04) %,( 26. 73 ± 1. 06) % and( 40. 46 ± 1. 25) %,respectively. All of these indicators were significantly different in the Ishikawa-M and-H groups compared to the Ishikawa-L group( P < 0. 05). Conclusion The effectiveness of progestogen therapy for AEH was associated with elevated TRIM22 expression.