IGF2 和 PCSK4 表达失衡与 NICTH 相关的 SFT 中 big IGF2 的过度产生有关：一项初步研究。

Imbalanced Expression of IGF2 and PCSK4 Is Associated With Overproduction of Big IGF2 in SFT With NICTH: A Pilot Study.

机构信息

First Department of Medicine, Wakayama Medical University, Wakayama, Japan.

Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.

出版信息

J Clin Endocrinol Metab. 2018 Jul 1;103(7):2728-2734. doi: 10.1210/jc.2018-00593.

DOI:10.1210/jc.2018-00593

PMID:29897468

Abstract

CONTEXT

Nonislet cell tumor hypoglycemia (NICTH) is a rare but serious paraneoplastic syndrome associated with large tumors. The high molecular weight IGF2, known as "big" IGF2, is produced by culprit tumors and leads to severe hypoglycemia. The detailed mechanism of its production in NICTH, however, remains unclear.

OBJECTIVE

To clarify the mechanism of production of big IGF2 in light of the processing of pro-IGF2 in patients with solitary fibrous tumor (SFT) and NICTH.

DESIGN

We enrolled 14 patients with SFT and divided them based on the presence or absence of hypoglycemia. In light of the processing of pro-IGF2 in SFT with hypoglycemia, we, retrospectively, compared the production levels of big IGF2 and the expression levels of IGF2 and proprotein convertase subtilisin/kexin type 4 (PCSK4), a proteolytic enzyme of pro-IGF2.

RESULTS

In all patients with NICTH, big IGF2 was detected in serum by western immunoblotting analysis. Moreover, we showed that two patients without hypoglycemia also had a small amount of big IGF2 in their serum. By immunohistochemical analysis, the protein expression level of IGF2 was significantly higher in the NICTH group than in the non-NICTH group (P = 0.043). The IGF2/PCSK4 protein expression-level ratio in the NICTH group was significantly higher than that in the non-NICTH group (P = 0.021).

CONCLUSION

In patients with SFT and hypoglycemia, an imbalance of IGF2 and PCSK4 expression could lead to increased serum levels of big IGF2.

摘要

背景

非胰岛细胞瘤性低血糖（NICTH）是一种罕见但严重的副肿瘤综合征，与大肿瘤有关。高分子量 IGF2 被称为“大”IGF2，是由罪魁祸首肿瘤产生的，导致严重的低血糖。然而，NICTH 中大 IGF2 的产生的详细机制尚不清楚。

目的

阐明孤立性纤维瘤（SFT）和 NICTH 患者前 IGF2 加工中产生大 IGF2 的机制。

设计

我们招募了 14 名患有 SFT 的患者，并根据是否存在低血糖将其分为两组。根据低血糖 SFT 中前 IGF2 的加工，我们回顾性地比较了大 IGF2 的产生水平以及 IGF2 和前蛋白转化酶枯草杆菌蛋白酶/kexin 类型 4（PCSK4）的表达水平，PCSK4 是前 IGF2 的一种蛋白水解酶。

结果

在所有 NICTH 患者中，通过 Western 免疫印迹分析在血清中检测到大 IGF2。此外，我们表明，两名无低血糖的患者血清中也有少量大 IGF2。通过免疫组织化学分析，NICTH 组 IGF2 的蛋白表达水平明显高于非 NICTH 组（P = 0.043）。NICTH 组 IGF2/PCSK4 蛋白表达水平比值明显高于非 NICTH 组（P = 0.021）。