目的:探究PTTG基因、Transgelin基因、SULT1A1基因、COMT基因在育龄期子宫肌瘤(Uterus Fibroid, UFs)患者的表达及临床意义,以期为临床上UFs的诊断和治疗提供新的思路和方法。方法:选择自2018年1月至2020年1月收入我院妇科的66例符合条件的子宫肌瘤患者为研究对象,并且选取同期32例因子宫脱垂而行子宫切除术的患者作为对照组,收集入组者的子宫组织和血清样本。利用RT-PCR检测样本中PTTG基因、Transgelin基因、SULT1A1基因、COMT基因的差异性表达,Logistic回归分析与子宫肌瘤相关的危险因素。结果:两组患者的BMI,妊娠史以及血清学指标雌激素(E2),促黄体生成素(LH),促卵泡激素(FSH)和孕酮(P)比较具有统计学差异(P < 0.05)。宫肌瘤组患者血清和子宫组织中PTTG基因、Transgelin基因、SULT1A1基因、COMT基因的mRNA相对表达量要明显低于正常对照组,比较具有统计学差异(P < 0.05)。Logistic分析结果显示,高BMI,有妊娠史,E2高水平,P高水平和PTTG基因、Transgelin基因、SULT1A1基因、COMT基因低表达是子宫肌瘤发生的高危因素(P < 0.05)。结论:雌激素(E2)和孕酮(P)含量的升高,PTTG基因、Transgelin基因、SULT1A1基因、COMT基因的降低与子宫肌瘤的发生密切相关,是临床上子宫肌瘤早期诊断和早期治疗新的靶点。 Objective: To explore the expression and clinical significance of PTTG gene, Transgelin gene, SULT1A1 gene and COMT gene in uterine leiomyoma (UFs), so as to provide new ideas and methods for clinical diagnosis and treatment of UFs. Methods: From January 2018 to January 2020, 66 patients with uterine fibroids in our hospital were selected as the research objects, and 32 patients who underwent hysterectomy due to uterine prolapse in the same period were selected as the control group. The uterine tissue and serum samples of the patients were collected. The RT-PCR was used to detect the differential expression of PTTG gene, Transgelin gene, SULT1A1 gene and COMT gene in the samples, and the basic information of patients was collected. Logistic regression analysis of risk factors associated with hysteromyoma. Results: There were significant differences in BMI, pregnancy history, serum estrogen (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone (P) between the two groups (P < 0.05). The relative mRNA expression levels of of PTTG gene, Transgelin gene, SULT1A1 gene and COMT gene in serum and uterine tissue of hysteromyoma group were significantly lower than those of normal control group (P < 0.05). The Logistic analysis showed that high BMI, history of pregnancy, high level of E2, high level of P and low expression of PTTG gene, Transgelin gene, SULT1A1 gene and COMT gene were the risk factors of uterine fibroids (P < 0.05). Conclusion: The increase of estrogen (E2) and progesterone (P), and the decrease of PTTG gene, Transgelin gene, SULT1A1gene and COMT gene are closely related to the occurrence of hysteromyoma. They are new targets for early diagnosis and treatment of hysteromyoma.
目的:探究PTTG基因、Transgelin基因、SULT1A1基因、COMT基因在育龄期子宫肌瘤(Uterus Fibroid, UFs)患者的表达及临床意义,以期为临床上UFs的诊断和治疗提供新的思路和方法。方法:选择自2018年1月至2020年1月收入我院妇科的66例符合条件的子宫肌瘤患者为研究对象,并且选取同期32例因子宫脱垂而行子宫切除术的患者作为对照组,收集入组者的子宫组织和血清样本。利用RT-PCR检测样本中PTTG基因、Transgelin基因、SULT1A1基因、COMT基因的差异性表达,Logistic回归分析与子宫肌瘤相关的危险因素。结果:两组患者的BMI,妊娠史以及血清学指标雌激素(E2),促黄体生成素(LH),促卵泡激素(FSH)和孕酮(P)比较具有统计学差异(P < 0.05)。宫肌瘤组患者血清和子宫组织中PTTG基因、Transgelin基因、SULT1A1基因、COMT基因的mRNA相对表达量要明显低于正常对照组,比较具有统计学差异(P < 0.05)。Logistic分析结果显示,高BMI,有妊娠史,E2高水平,P高水平和PTTG基因、Transgelin基因、SULT1A1基因、COMT基因低表达是子宫肌瘤发生的高危因素(P < 0.05)。结论:雌激素(E2)和孕酮(P)含量的升高,PTTG基因、Transgelin基因、SULT1A1基因、COMT基因的降低与子宫肌瘤的发生密切相关,是临床上子宫肌瘤早期诊断和早期治疗新的靶点。
子宫肌瘤,非编码RNA,性激素,相关性
Cuihua Lu
Department of Obstetrics and Gynecology, Shan County Central Hospital, Heze Shandong
Received: Jun. 17th, 2022; accepted: Jul. 21st, 2022; published: Jul. 28th, 2022
Objective: To explore the expression and clinical significance of PTTG gene, Transgelin gene, SULT1A1 gene and COMT gene in uterine leiomyoma (UFs), so as to provide new ideas and methods for clinical diagnosis and treatment of UFs. Methods: From January 2018 to January 2020, 66 patients with uterine fibroids in our hospital were selected as the research objects, and 32 patients who underwent hysterectomy due to uterine prolapse in the same period were selected as the control group. The uterine tissue and serum samples of the patients were collected. The RT-PCR was used to detect the differential expression of PTTG gene, Transgelin gene, SULT1A1 gene and COMT gene in the samples, and the basic information of patients was collected. Logistic regression analysis of risk factors associated with hysteromyoma. Results: There were significant differences in BMI, pregnancy history, serum estrogen (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone (P) between the two groups (P < 0.05). The relative mRNA expression levels of of PTTG gene, Transgelin gene, SULT1A1 gene and COMT gene in serum and uterine tissue of hysteromyoma group were significantly lower than those of normal control group (P < 0.05). The Logistic analysis showed that high BMI, history of pregnancy, high level of E2, high level of P and low expression of PTTG gene, Transgelin gene, SULT1A1 gene and COMT gene were the risk factors of uterine fibroids (P < 0.05). Conclusion: The increase of estrogen (E2) and progesterone (P), and the decrease of PTTG gene, Transgelin gene, SULT1A1gene and COMT gene are closely related to the occurrence of hysteromyoma. They are new targets for early diagnosis and treatment of hysteromyoma.
Keywords:Hysteromyoma, Non Coding RNA, Sex Hormone, Relevance
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子宫平滑肌瘤(UFs)是妇产科常见的一种良性肿瘤性疾病,其病理特点是平滑肌细胞增生和细胞外基质(ECM)过度沉积 [
近年来LncRNA与临床疾病相关性研究是目前的热点问题,比如有学者认为lncRNA与胚胎发育,胃肠肿瘤的侵袭和增殖以及组织纤维化等密切相关 [
本研究选择自2018年1月至2020年1月收入我院妇科的66例符合条件的子宫肌瘤患者为研究对象,并且选取同期32例因子宫脱垂而行子宫切除术的患者作为对照组,收集入组者的子宫组织和血清样本。所有患者均签署知情同意书,符合本院伦理学要求。
统计并记录患者的一般基准资料,比如性别,年龄,身高,体重,既往高血压病史,糖尿病病史,冠心病病史和血清学指标,包括雌激素(E2),促黄体生成素(LH),促卵泡激素(FSH)和孕酮(P)等。
① 经B超诊断为子宫肌瘤,瘤体大小 > 5 cm,并且伴有临床症状,比如月经的改变,腹痛,腹胀,肛门坠胀感等,就需要手术切除;
② 子宫脱垂的患者无其他子宫疾病,无炎症改变;
③ 入组者无明显的心肺功能疾病,比如肺功能不全,心功能不全,肾功能不全等疾病,可以耐受手术治疗;
④ 入组者患者无血液类疾病,比如再生障碍性贫血,白血病,凝血功能障碍等疾病,术后出血发生率极高;
⑤ 入组者无严重的心理疾病,包括人格分裂等心理疾病;
⑥ 入组者均对研究的内容和目的,同意研究方案,并签署知情同意书。
① 子宫肌瘤的瘤体大小 < 5 cm,并且不存在临床症状的患者,可以保守治疗;
② 诊断不明确的患者,比如子宫腺肌病患者;
③ 心肺功能不全的子宫肌瘤患者;
④ 不同意该研究方案,拒绝服从医护指导的患者;
⑤ 未签署知情同意书的患者。
收集子宫肌瘤患者的子宫肌瘤组织及样本,子宫脱垂患者的正常子宫组织和血清标本,置于液氮中迅速冷冻,然后置入−80℃低温冰箱中保存。
收集1 mg子宫肌瘤组织和正常子宫组织,加入1 mL Trizol溶剂,提取细胞总RNA,保证RNA纯度范围为1.8~2.1,然后利用TaKaRa逆转录试剂盒的要求,采用20 μL反应体系逆转录为cDNA,−80℃保存,采用TAKARA荧光定量PCR试剂盒的要求,采用FTC-2000 RT-PCR系统和50 μg反应体系对样本DNA进行分析,溶解曲线确定Tm值为53.7℃,统计并记录各组样本的CT值,采用2−ΔΔCT法对PTTG基因、Transgelin基因、SULT1A1基因、COMT基因的mRNA相对表达水平,见表1。
收集月经周期第6天的空腹静脉血,利用ELISA试剂盒检测血清中的激素(E2),促黄体生成素(LH),促卵泡激素(FSH)和孕酮(P)等。
靶基因 | 序列 | |
---|---|---|
PTTG基因 | 正义链 | 5’-CTTGACTGCATGCCTTTGTGGAACT-3’ |
反义链 | 5’-TTAGCGCAGCCAGGAGAAATCAAAC-3’ | |
Transgelin基因 | 正义链 | 5’-AGATTCGCCTGCGCGAGTTTGAGCCG-3’ |
反义链 | 5’-CCATCGGCTTGCAATGTCAGTCGTCCT-3’ | |
SULT1A1基因 | 正义链 | 5’-CCTAATGCTGCGTGCAGATGCGTTTCAT-3’ |
反义链 | 5’-GAGACACTTGCCGTGTGCAGCTTCTTG-3’ | |
COMT基因 | 正义链 | 5’-ATTGCGTGCATGTGCAAATGCGTTTCAT-3’ |
反义链 | 5’-GTGCGTGCGTGCGTGAATGCGTAACTTG-3’ | |
GAPDH | 正义链 | 5’-GCACCGTCTTGCGCTGCTGAGAGAAC-3’ |
反义链 | 5’-GCTGGTGTGTGGCAACGTGCAGTGGA-3’ |
表1. PTTG基因、Transgelin基因、SULT1A1基因、COMT基因和内参GAPDH的基因序列
利用SPSS 23.0软件进行分析,计量资料采用(x ± s),计数资料采用率进行比较。子宫肌瘤组子宫组织和对照组正常子宫组织以及血清中的PTTG基因、Transgelin基因、SULT1A1基因、COMT基因的mRNA相对表达量比较采用t检验。用Pearson法分析PTTG基因、Transgelin基因、SULT1A1基因、COMT基因与血清中的激素(E2),促黄体生成素(LH),促卵泡激素(FSH)和孕酮(P)的相关性;采用受试者工作特征曲线(ROC),计算曲线下面积(AUC)、灵敏度、特异度,预测PTTG基因、Transgelin基因、SULT1A1基因、COMT基因对子宫肌瘤的诊断价值,P < 0.05为差异有统计学意义。
结果显示,两组患者的年龄,吸烟饮酒史,高血压糖尿病史比较无统计学差异(P > 0.05),两组患者的BMI,妊娠史以及血清学指标雌激素(E2),促黄体生成素(LH),促卵泡激素(FSH)和孕酮(P)比较具有统计学差异(P < 0.05),见表2。
指标 | 子宫肌瘤组(n = 66) | 对照组(n = 32) | t/c2值 | P值 | ||
---|---|---|---|---|---|---|
年龄 | 53.34 ± 3.27 | 53.54 ± 4.56 | 0.329 | >0.05 | ||
BMI (Kg/m2) | 27.43 ± 2.09 | 22.08 ± 1.23 | 2.806 | <0.05 | ||
吸烟史 | 6/66 (9.09%) | 4/32 (12.50%) | 0.679 | >0.05 | ||
饮酒史 | 10/66 (15.15%) | 4/32 (12.50%) | 0.547 | >0.05 | ||
妊娠史 | 61/66 (92.42%) | 16/32 (50.00%) | 2.011 | <0.05 | ||
高血压病史 | 7/66 (10.61%) | 4/32 (12.50%) | 0.432 | >0.05 | ||
糖尿病史 | 4/66 (6.06%) | 2/32 (6.25%) | 0.244 | >0.05 | ||
E2(pmol/L) | 323.43 ± 89.45 | 123.54 ± 30.54 | 2.891 | <0.05 | ||
LH (IU/L) | 21.03 ± 1.05 | 12.08 ± 1.04 | 2.198 | <0.05 | ||
FSH (μg/L) | 32.14 ± 4.23 | 12.09 ± 3.89 | 3.902 | <0.05 | ||
P (nmol/L) | 24.35 ± 3.14 | 10.03 ± 4.22 | 2.893 | <0.05 | ||
表2. 子宫肌瘤组患者和正常对照组患者的一般基准资料比较结果
结果显示,子宫肌瘤组患者血清中PTTG基因、Transgelin基因、SULT1A1基因、COMT基因的mRNA相对表达量要明显低于正常对照组,比较具有统计学差异(P < 0.05),见表3。
指标 | 子宫肌瘤组(n = 66) | 对照组(n = 32) | t值 | P值 |
---|---|---|---|---|
LncRNA ATB | 0.41 ± 0.03 | 1.09 ± 0.23 | 2.426 | <0.05 |
LncRNA GAS5 | 0.25 ± 0.01 | 1.03 ± 0.14 | 2.873 | <0.05 |
LncRNA P21 | 0.33 ± 0.09 | 1.12 ± 0.35 | 2.735 | <0.05 |
LncRNA MEG3 | 0.32 ± 0.03 | 1.09 ± 0.16 | 2.208 | <0.05 |
表3. 子宫肌瘤组患者和正常对照组患者血清中PTTG基因、Transgelin基因、SULT1A1基因、COMT基因的mRNA相对表达水平
结果显示,高BMI,有妊娠史,E2高水平,P高水平和PTTG基因、Transgelin基因、SULT1A1基因、COMT基因低表达是子宫肌瘤发生的高危因素(P < 0.05),见表4。
指标 | β | SE | Wald | P | OR | 95%CI |
---|---|---|---|---|---|---|
BMI指数较高 | 0.863 | 0.579 | 5.009 | 0.016 | 2.897 | 1.044~3.215 |
存在妊娠史 | 0.914 | 0.633 | 3.228 | 0.011 | 3.144 | 2.004~4.746 |
E2高水平 | 0.998 | 0.459 | 2.289 | 0.029 | 2.934 | 1.290~4.903 |
LH高水平 | 0.927 | 0.533 | 1.078 | 0.098 | 2.223 | 2.894~2.914 |
FSH高水平 | 0.229 | 0.539 | 1.908 | 0.121 | 2.342 | 2.457~3.914 |
P高水平 | 0.198 | 0.674 | 3.908 | 0.021 | 3.902 | 0.887~3.998 |
LncRNA ATB低表达 | 0.593 | 0.776 | 4.998 | 0.017 | 2.398 | 1.543~4.367 |
LncRNA GAS5低表达 | 0.549 | 0.432 | 3.598 | 0.001 | 2.893 | 1.457~3.478 |
LncRNA P21低表达 | 0.608 | 0.409 | 5.559 | 0.000 | 2.239 | 1.479~2.923 |
LncRNA MEG3低表达 | 0.647 | 0.399 | 4.893 | 0.000 | 2.873 | 1.666~3.349 |
表4. 与子宫肌瘤发生相关的Logistic回归分析结果
子宫肌瘤(UFs)是临床上的常见疾病,与腹部的疼痛和月经量过多密切相关。同时,UFs是一种性类固醇激素依赖性良性肿瘤,一些观察性研究已经检验了肥胖和UFs风险之间的关系,在一项Meta分析研究中,根据纳入标准和排除标准,共选取了22篇文章,包括325,899名参与者和19,593例对照者。他们的研究结果表明,发现肥胖与UFs的风险/患病率呈正相关(OR:1.19;95%CI:1.09至1.29)。BMI最高的入组者与BMI正常的入组者相比,OR值为1.19 (1.09至1.31)。此外,他们的研究结果表明BMI与UFs风险的关系是一个逆J型模式。并且肥胖是子宫肌瘤发生的独立危险因素 [
也有研究表明,许多生物小分子物质与子宫肌瘤的发生密切相关,比如miRNA-217,miRNA-18a等 [
此外,在本研究中,我们发现子宫肌瘤患者血清中雌激素(E2),促黄体生成素(LH),促卵泡激素(FSH)和孕酮(P)的含量要明显高于对照组(P < 0.05)。从而证明性激素在子宫肌瘤发生和发展中起到十分重要的作用。更进一步,利用logistic分析与子宫肌瘤发生相关的因素,结果显示,高BMI,有妊娠史,E2高水平,P高水平和PTTG基因、Transgelin基因、SULT1A1基因、COMT基因低表达是子宫肌瘤发生的高危因素(P < 0.05)。
综上所述,雌激素(E2)和孕酮(P)含量的升高,PTTG基因、Transgelin基因、SULT1A1基因、COMT基因的降低与子宫肌瘤的发生密切相关,是临床上子宫肌瘤早期诊断和早期治疗新的靶点
卢翠华. PTTG基因、Transgelin基因、SULT1A1基因、COMT基因在育龄期子宫肌瘤患者中的表达及临床意义研究Expression and Clinical Significance of PTTG Gene, Transgelin Gene, SULT1A1 Gene and COMT Gene in Uterine Leiomyoma Patients in Child-Bearing Period[J]. 外科, 2022, 11(03): 95-101. https://doi.org/10.12677/HJS.2022.113016
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