Imbalanced Expression of IGF2 and PCSK4 is Associated with Overproduction of Big IGF2 in SFT with NICTH: A Pilot Study.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM(2018)
摘要
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 nonNICTH 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.
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