Expression levels of peripheral blood circular RNA ATRNL1 and follistatin in patients with endometrial polyp and their predictive value for recurrence after hysteroscopic resection

doi:10.3877/cma.j.issn.1673-5250.2026.02.006

Objective

To investigate the expression levels of circular RNA (circRNA) ATRNL1 and follistatin (FST) in peripheral blood of patients with endometrial polyp (EP), and to evaluate their ability to predict recurrence within 6 months after hysteroscopic electrosurgical resection.

Methods

A total of 85 patients with EP who underwent hysteroscopic resection at the People′s Hospital of Danyang from January to April in 2024 were enrolled and followed up for 6 months postoperatively. A retrospective analysis was conducted. According to whether the patients experienced a recurrence of EP within 6 months after surgery, they were divided into recurrence group (n=12) and non-recurrence group (n=73). The t test and chi-square test were applied to compare the general clinical data and serum levels of circATRNL1 and FST between two groups. Additionally, serum follicle-stimulating hormone (FSH), estradiol, luteinizing hormone (LH), relative expression levels of transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF) in endometrial tissue, as well as endometrial thickness before and 6 months after surgery, were compared inter-group and intra-group. Multivariate unconditional logistic regression analysis was conducted to identify independent risk factors for postoperative recurrence. Receiver operating characteristic (ROC) curves were constructed to assess the predictive value of serum circATRNL1 and FST individually and in combination. This study was approved by the Ethics Committee of the People′s Hospital of Danyang (Approval No. 20250430), and informed consent was obtained from all participants.

Results

① Serum circATRNL1 and FST levels of EP patients in recurrence group were higher than those in non-recurrence group, and the differences were statistically significant (P<0.05). ② Inter-group comparison showed that at 6 months after surgery, the serum levels of FSH, estradiol, and LH, relative expression level of TGF-β in endometrial tissue, and endometrial thickness of EP patients in recurrence group were higher or thicker than those in non-recurrence group, and the differences were statistically significant (P<0.05). Intra-group comparison showed that, in both groups, these 5 parameters above as well as relative expression level of VEGF in endometrial tissue at 6 months after surgery were lower than those before surgery, and the differences were statistically significant (P<0.05). ③ Multivariate unconditional logistic regression analysis demonstrated that elevated serum circATRNL1 level (OR=4.080, 95%CI: 1.745-9.539, P=0.005), elevated serum FST level (OR=4.536, 95%CI: 1.939-10.605, P=0.004), elevated serum FSH level (OR=4.563, 95%CI: 1.952-10.669, P=0.006), elevated serum estradiol level (OR=5.028, 95%CI: 2.150-11.756, P=0.006), elevated serum LH level (OR=4.604, 95%CI: 1.969-10.765, P=0.003), higher expression level of TGF-β in endometrial tissue (OR=4.865, 95%CI: 2.081-11.374, P=0.002), and greater endometrial thickness (OR=4.914, 95%CI: 2.101-11.488, P=0.007) were all independent risk factors for EP recurrence within 6 months after surgery. ④ ROC curve analysis showed that the sensitivity of serum circATRNL1 level, serum FST level, and their combination in predicting EP recurrence within 6 months after hysteroscopic resection were 75.0%, 72.2%, and 75.0%, respectively, while the specificity values were 76.7%, 64.4%, and 84.9%, respectively. The corresponding area under the curve (AUC) were 0.819 (95%CI: 0.738-0.899), 0.724 (95%CI: 0.615-0.833), and 0.842 (95%CI: 0.759-0.925), respectively.

Conclusions

Abnormally elevated levels of circATRNL1 and FST in peripheral blood are associated with the progression of EP, and demonstrate potential value in predicting EP recurrence within 6 months after hysteroscopic resection.

Key words: Endometrial hyperplasia, RNA, circular, Follistatin, ROC curve, Recurrence, Risk factors, Female

表1 2组EP患者一般临床资料及术前血清circATRNL1、FST水平比较

组别	例数	年龄(岁，±s)	病程(月，±s)	息肉最大径(mm，±s)	息肉为单发[例数(%)]	剖宫产术分娩史[例数(%)]	术前血清circATRNL1相对表达量(±s)	术前血清FST(μg/L，±s)
复发组	12	32.1±4.6	13.1±2.5	16.1±2.8	5(41.7)	9(75.0)	2.4±0.4	3.7±0.5
未复发组	73	33.2±4.1	12.8±2.1	14.9±3.0	33(45.2)	48(65.8)	1.3±0.3	2.0±0.4
统计量		t＝0.86	t＝0.37	t＝1.22	χ²＝0.05	χ²＝0.40	t＝11.09	t＝13.74
P值		0.391	0.710	0.225	0.819	0.528	<0.001	<0.001

表1 2组EP患者一般临床资料及术前血清circATRNL1、FST水平比较

组别	例数	年龄(岁，±s)	病程(月，±s)	息肉最大径(mm，±s)	息肉为单发[例数(%)]	剖宫产术分娩史[例数(%)]	术前血清circATRNL1相对表达量(±s)	术前血清FST(μg/L，±s)
复发组	12	32.1±4.6	13.1±2.5	16.1±2.8	5(41.7)	9(75.0)	2.4±0.4	3.7±0.5
未复发组	73	33.2±4.1	12.8±2.1	14.9±3.0	33(45.2)	48(65.8)	1.3±0.3	2.0±0.4
统计量		t＝0.86	t＝0.37	t＝1.22	χ²＝0.05	χ²＝0.40	t＝11.09	t＝13.74
P值		0.391	0.710	0.225	0.819	0.528	<0.001	<0.001

表2 2组EP患者6项指标术前及术后6个月水平的组间及组内比较(

±s)

组别	例数	血清FSH(IU/L)				血清雌二醇(pg/mL)
组别	例数	术前	术后6个月	t值	P值	术前	术后6个月	t值	P值
复发组	12	7.4±1.6	5.4±1.2	3.56	0.005	164.3±26.3	105.0±12.4	6.99	<0.001
未复发组	73	7.3±1.5	4.2±1.2	13.61	<0.001	161.1±23.7	92.0±12.4	21.61	<0.001
t值		0.15	3.18			0.42	3.35
P值		0.885	0.002			0.675	0.001
组别	例数	血清LH(IU/L)				子宫内膜组织TGF-β相对表达量
组别	例数	术前	术后6个月	t值	P值	术前	术后6个月	t值	P值
复发组	12	6.9±1.3	5.7±2.0	3.51	0.010	139.1±26.5	118.5±19.1	2.57	0.043
未复发组	73	7.1±1.5	4.0±1.6	12.31	<0.001	138.4±25.7	104.2±18.7	8.82	<0.001
t值		0.47	3.22			0.08	2.44
P值		0.639	0.002			0.938	0.018
组别	例数	子宫内膜组织VEGF相对表达量				子宫内膜厚度(mm)
组别	例数	术前	术后6个月	t值	P值	术前	术后6个月	t值	P值
复发组	12	137.6±19.3	106.9±20.6	3.67	0.004	16.6±2.5	9.5±2.2	7.26	<0.001
未复发组	73	135.5±20.1	95.9±21.9	11.02	<0.001	16.0±2.1	8.3±1.7	24.13	<0.001
t值		0.34	1.62			0.83	2.22
P值		0.739	0.108			0.407	0.029

表2 2组EP患者6项指标术前及术后6个月水平的组间及组内比较(

±s)

组别	例数	血清FSH(IU/L)				血清雌二醇(pg/mL)
组别	例数	术前	术后6个月	t值	P值	术前	术后6个月	t值	P值
复发组	12	7.4±1.6	5.4±1.2	3.56	0.005	164.3±26.3	105.0±12.4	6.99	<0.001
未复发组	73	7.3±1.5	4.2±1.2	13.61	<0.001	161.1±23.7	92.0±12.4	21.61	<0.001
t值		0.15	3.18			0.42	3.35
P值		0.885	0.002			0.675	0.001
组别	例数	血清LH(IU/L)				子宫内膜组织TGF-β相对表达量
组别	例数	术前	术后6个月	t值	P值	术前	术后6个月	t值	P值
复发组	12	6.9±1.3	5.7±2.0	3.51	0.010	139.1±26.5	118.5±19.1	2.57	0.043
未复发组	73	7.1±1.5	4.0±1.6	12.31	<0.001	138.4±25.7	104.2±18.7	8.82	<0.001
t值		0.47	3.22			0.08	2.44
P值		0.639	0.002			0.938	0.018
组别	例数	子宫内膜组织VEGF相对表达量				子宫内膜厚度(mm)
组别	例数	术前	术后6个月	t值	P值	术前	术后6个月	t值	P值
复发组	12	137.6±19.3	106.9±20.6	3.67	0.004	16.6±2.5	9.5±2.2	7.26	<0.001
未复发组	73	135.5±20.1	95.9±21.9	11.02	<0.001	16.0±2.1	8.3±1.7	24.13	<0.001
t值		0.34	1.62			0.83	2.22
P值		0.739	0.108			0.407	0.029

表3 影响EP患者宫腔镜下电切术后6个月内复发的多因素非条件logistic回归分析结果

影响因素	B	SE	Wald值	P值	OR值	OR值95%CI
血清circATRNL1水平	1.406	0.672	4.378	0.005	4.080	1.745~9.539
血清FST水平	1.512	0.693	4.760	0.004	4.536	1.939~10.605
血清FSH水平	1.514	0.754	4.053	0.006	4.563	1.952~10.669
血清雌二醇水平	1.615	0.802	4.055	0.006	5.028	2.150~11.756
血清LH水平	1.527	0.683	4.998	0.003	4.604	1.969~10.765
子宫内膜组织TGF-β相对表达量	1.582	0.693	5.211	0.002	4.865	2.081~11.374
子宫内膜厚度	1.592	0.795	4.010	0.007	4.914	2.101~11.488
常数项	－1.787	1.259	2.015	0.156	－	－

表3 影响EP患者宫腔镜下电切术后6个月内复发的多因素非条件logistic回归分析结果

影响因素	B	SE	Wald值	P值	OR值	OR值95%CI
血清circATRNL1水平	1.406	0.672	4.378	0.005	4.080	1.745~9.539
血清FST水平	1.512	0.693	4.760	0.004	4.536	1.939~10.605
血清FSH水平	1.514	0.754	4.053	0.006	4.563	1.952~10.669
血清雌二醇水平	1.615	0.802	4.055	0.006	5.028	2.150~11.756
血清LH水平	1.527	0.683	4.998	0.003	4.604	1.969~10.765
子宫内膜组织TGF-β相对表达量	1.582	0.693	5.211	0.002	4.865	2.081~11.374
子宫内膜厚度	1.592	0.795	4.010	0.007	4.914	2.101~11.488
常数项	－1.787	1.259	2.015	0.156	－	－

图1 血清circATRNL1、FST水平单独及联合预测EP患者宫腔镜下电切术后6个月内复发的ROC曲线注：circATRNL1为环状RNA ATRNL1，FST为卵泡抑素，EP为子宫内膜息肉，ROC曲线为受试者工作特征曲线

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