Abstract 795: GDF15, the putative mitokine factor, promotes tumor progression in thyroid cancer via STAT3 regulation

Abstract

Abstract Purpose: As mitochondrial dysfunction is an integral component during the initial stages of tumorigenesis, mechanistic insight on the interaction between these two pathways may lead to novel therapeutic approaches. The aim of this study is to investigate the role of GDF15, the putative mitokine factor in thyroid tumorigenesis. Methods: Expression levels of GDF15 was investigated using The Cancer Genome Atlas database. The role of GDF15 in tumor aggressiveness was investigated by analyzing the effects of knock-down of GDF15 on proliferation, migration, and invasion of thyroid cancer cells. Serum levels of GDF15 were measured in healthy subjects and patients with papillary thyroid cancer (PTC), and expression of GDF15 by IHC was investigated in PTC samples. To investigate the exact mechanism of GDF15 in thyroid cancer, both IPA analysis and GSEA analysis were performed using TCGA database and RNA seq data from Chungnam national university hospital. Results: TCGA data revealed the higher expression of GDF15 in tumor samples compared to in paired non-tumor samples. Thyroid cancer cells with knock-down of GDF15 revealed the decrease of proliferation, migration, and invasion compared to control cells via regulation of STAT3. Higher serum levels of GDF15 were found in patients with thyroid cancer than in control participants, and were significantly associated with tumor stage, lymphovascular invasion, and recurrence. In addition, patients with high GDF15 expression by IHC revealed the aggressive phenotype compared to patients with low GDF15 expression. Conclusions: GDF15 is a new biomarker for predicting tumor progression, and therapies targeting GDF15 may be effective for treating thyroid cancer. Citation Format: Yea Eun Kang, Jae Won Chang, Lihua Liu, Kyoungmin Lee, Mi Ae Lim, Seung-Nam Jung, Chan Oh, Ho-Ryun Won, Minho Shong, Bon Seok Koo. GDF15, the putative mitokine factor, promotes tumor progression in thyroid cancer via STAT3 regulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 795.