中国全科医学

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类固醇生成因子1表达水平与垂体腺瘤患者激素水平的关系及对术后复发预测价值研究

董伟1,董晓柳2*,张利1,张欢1,张于3   

  1. 1.063000 河北省唐山市人民医院神经外科;2.063000 河北省唐山市人民医院神经内科;3.063000 河省唐山市人民医院重症医学科
  • 收稿日期:2025-04-28 修回日期:2025-08-22 接受日期:2025-09-26
  • 通讯作者: 董晓柳,副主任医师;E-mail:12128012@qq.com
  • 基金资助:
    2022年河北省自然科学基金资助项目(精准医学联合基金培育项目)(H2022105014)

Relationship between Steroidogenic Factor-1 Expression and Hormone Levels in Patients with Pituitary Adenoma and Its Predictive Value for Postoperative Recurrence

DONG Wei1, DONG Xiaoliu2*, ZHANG Li1, ZHANG Huan1, ZHANG Yu3   

  1. 1.Department of Neurosurgery, Tangshan People's Hospital, Tangshan 063000, China;2. Department of Neurology, Tangshan People's Hospital, Tangshan 063000, China;3. Department of Critical Care Medicine, Tangshan People's Hospital, Tangshan 063000, China
  • Received:2025-04-28 Revised:2025-08-22 Accepted:2025-09-26
  • Contact: DONG Xiaoliu, Deputy chief physician;E-mail: 12128012@qq.com

摘要: 背景 部分垂体腺瘤(PA)对药物不敏感,需要寻找针对垂体相关转录因子的干预手段;对于类固醇生成因子(SF-1)表达水平对PA全切术后的预测价值尚缺乏深入分享。目的 分析SF-1表达水平与激素水平的关系及二者对PA患者术后的预测价值。方法 前瞻性选取2022年5月—2023年3月在唐山市人民医院诊断为PA患者104例为研究对象,进行全切术治疗,检测PA组织及癌旁组织中SF-1 mRNA相对表达水平。根据患者SF-1 mRNA表达水平将患者分为SF-1 mRNA低表达组(n=49)与SF-1 mRNA高表达组(n=55),比较两组的基本资料及激素水平。以激素指标为自变量,以SF-1 mRNA水平为因变量进行分层回归分析,分析不同激素对SF-1 mRNA表达水平的影响。根据术后预后情况将患者分为复发组(n=40)与未复发组(n=64),分析SF-1 mRNA表达水平对术后复发的影响。绘制SF-1 mRNA表达水平预测PA患者术后复发的ROC。绘制限制性立方样条图并进行阈值效应分析。绘制Kaplan-Meier生存曲线,分析SF-1 mRNA表达水平与PA患者术后复发的关系。结果 SF-1mRNA在PA组织中的表达水平(1.05±0.21)高于癌旁组织(0.38±0.07)(t=30.867,P<0.05)。SF-1 mRNA高表达组生长激素(GH)、人前梯度蛋白2(AGR2)、催乳素(PRL)、促甲状腺激素(TSH)及促肾上腺皮质激素(ACTH)水平高于SF-1 mRNA低表达组(P<0.05)。分层回归分析显示,GH、AGR2、PRL、TSH及ACTH对SF-1 mRNA表达水平产生正向影响(P<0.05)。复发组与未复发组SF-1 mRNA表达水平、肿瘤分期、组织分化、GH、AGR2、PRL及ACTH比较,差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,调整各因素前后,SF-1 mRNA表达水平均是PA患者术后复发的影响因素(P<0.05)。SF-1 mRNA表达水平预测PA患者术后复发的AUC为0.705(95%CI=0.604~0.806,P<0.005),最佳截断值为0.87,灵敏度为0.806,特异度为0.634。限制性立方样条图显示,SF-1 mRNA表达水平影响PA患者术后复发的拐点为0.87,拐点前后的OR分别为1.006(95%CI=1.002~1.011,P=0.026)和1.007(95%CI=1.005-1.009,P=0.017),PA患者术后复发的风险随着SF-1 mRNA表达水平的增加而增加。Kaplan-Meier生存曲线显示,SF-1mRNA高表达组无复发生存期为15个月(95%CI=11.16~18.43),SF-1 mRNA低表达组SF-1 mRNA无复发生存期为28个月(95%CI=23.54~31.54),Log-rank检验结果显示两组组间差异有统计学意义(χ2=7.861,P<0.001)。结论 SF-1 mRNA在PA组织中表达显著上调,其高表达与患者GH、AGR2、PRL、TSH及ACTH水平升高独立相关。SF-1mRNA表达水平可作为评估PA患者激素分泌状态及预测术后复发风险的潜在生物标志物,联合GH、AGR2等激素指标检测可能提升预测效能。

关键词: 垂体腺瘤, 类固醇生成因子 1, 激素, 预后, 术后预测

Abstract: Background Some pituitary adenomas (PA) are resistant to medical therapy, motivating investigation of pituitaryrelated transcription factors as therapeutic targets. The prognostic value of steroidogenic factor1 (SF1) expression for postoperative outcomes in PA remains underexplored. Objective To analyze the relationship between SF1 expression and hormone levels and to evaluate their value in predicting postoperative recurrence in PA patients. Methods In this prospective study, 104 patients diagnosed with PA at Tangshan People's Hospital between May 2022 and March 2023 who underwent gross total resection were enrolled. Relative SF1 mRNA expression was measured in PA tissue and adjacent nontumorous tissue. Based on SF1 mRNA levels, patients were grouped into low expression (n=49) and high expression (n=55) cohorts. Baseline characteristics and hormone profiles were compared between groups. Stratified regression analyses were performed using hormone indices as independent variables and SF1 mRNA level as the dependent variable to evaluate hormonal influences on SF-1 expression. Patients were also classified by postoperative outcome into recurrence (n=40) and nonrecurrence (n=64) groups to assess the association between SF1 mRNA expression and recurrence. Receiver operating characteristic (ROC) analysis, restricted cubic spline (RCS) modeling with thresholdeffect analysis, and Kaplan-Meier survival analysis were used to evaluate predictive performance and recurrencefree survival. Results SF1 mRNA expression was significantly higher in PA tissue (1.05±0.21) than in adjacent tissue (0.38±0.07) (t=30.867, P<0.05). The SF1 highexpression group exhibited higher levels of growth hormone (GH), anterior gradient 2 (AGR2), prolactin (PRL), thyroidstimulating hormone (TSH), and adrenocorticotropic hormone (ACTH) compared with the lowexpression group (P<0.05). Stratified regression identified GH, AGR2, PRL, TSH, and ACTH as positive predictors of SF1 mRNA expression (P<0.05). Comparisons between recurrence and nonrecurrence groups demonstrated statistically significant differences in SF1 mRNA expression, tumor stage, histological differentiation, GH, AGR2, PRL, and ACTH (P<0.05). Multivariate logistic regression indicated that SF1 mRNA expression remained an independent predictor of postoperative recurrence after adjustment for covariates (P<0.05). The area under the curve (AUC) for SF1 mRNA predicting postoperative recurrence was 0.705 (95%CI=0.604-0.806; P<0.005); the optimal cutoff was 0.87, yielding sensitivity 0.806 and specificity 0.634. RCS analysis identified an inflection point at SF1=0.87; the odds ratios (OR) for recurrence per unit increase in SF1 mRNA were 1.006 (95%CI=1.002-1.011, P=0.026) before the inflection and 1.007 (95%CI=1.005-1.009, P=0.017) after it, indicating a rising recurrence risk with increasing SF1 expression. Kaplan-Meier analysis showed median recurrencefree survival of 15 months (95%CI=11.16-18.43) in the SF1 highexpression group versus 28 months (95%CI=23.54-31.54) in the lowexpression group; the difference was significant by logrank test (χ2 =7.861, P<0.001). Conclusion SF1 mRNA is markedly upregulated in PA tissue and its high expression is independently associated with elevated GH, AGR2, PRL, TSH, and ACTH levels. SF1 mRNA expression may serve as a potential biomarker to assess hormonal status and predict postoperative recurrence risk in PA patients; combined assessment with hormones such as GH and AGR2 may improve predictive accuracy.

Key words: Pituitary adenoma, Steroidogenic factor 1, Hormone, Prognosis, Postoperative prognosis

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