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肢端肥大症患者经蝶窦手术后血清蛋白质组变化:疾病活动的新生物标志物。

Serum proteome changes in acromegalic patients following transsphenoidal surgery: novel biomarkers of disease activity.

机构信息

Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA.

出版信息

Eur J Endocrinol. 2011 Feb;164(2):157-67. doi: 10.1530/EJE-10-0754. Epub 2010 Nov 8.

Abstract

CONTEXT

Transsphenoidal adenomectomy is the primary treatment for acromegaly. However, assessment of the therapeutical outcome remains problematic since the existing biomarkers of disease activity frequently show discordant results.

OBJECTIVE

To discover novel serum biomarkers of disease activity in acromegalic patients before and after surgery.

DESIGN

Serum samples of eight newly diagnosed acromegaly patients before and after transsphenoidal surgery were analyzed for proteomic changes by two-dimensional gel electrophoresis. Protein spots displaying statistically significant changes, pre- versus post-surgery, were identified by mass spectrometry (MS), tandem MS (MS/MS), and western blot analysis.

RESULTS

Six protein spots displaying decreased intensities after surgery were identified as transthyretin (two isoforms), haptoglobin α2, β-hemoglobin, and apolipoprotein A-1 (two isoforms). One protein spot, identified as complement C4B precursor, was increased after the surgery.

CONCLUSIONS

Seven serum protein spots were differentially expressed following surgery in acromegalic patients. The identified proteins represent potential novel biomarkers to assess the effectiveness of surgical treatment in acromegalic individuals. Future studies will validate the use of the identified proteins as biomarkers of disease activity after medical treatment of acromegaly.

摘要

背景

经蝶窦腺瘤切除术是肢端肥大症的主要治疗方法。然而,治疗效果的评估仍然存在问题,因为现有的疾病活动生物标志物经常显示出不一致的结果。

目的

发现新的肢端肥大症患者手术前后疾病活动的血清生物标志物。

设计

通过二维凝胶电泳分析 8 例新诊断的肢端肥大症患者手术前后的血清蛋白质组变化。通过质谱(MS)、串联质谱(MS/MS)和 Western blot 分析鉴定显示术前与术后统计学显著变化的蛋白质斑点。

结果

手术后有 6 个蛋白质斑点的强度降低,被鉴定为转甲状腺素(两种同工型)、触珠蛋白α2、β-血红蛋白和载脂蛋白 A-1(两种同工型)。一个蛋白质斑点,被鉴定为补体 C4B 前体,手术后增加。

结论

在肢端肥大症患者手术后,有 7 个血清蛋白斑点的表达不同。鉴定出的蛋白质代表评估肢端肥大症个体手术治疗效果的潜在新的生物标志物。未来的研究将验证所鉴定的蛋白质作为肢端肥大症药物治疗后疾病活动的生物标志物的用途。

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