Gene Expression Network Analysis of ETV1 Reveals KCTD10 as a Novel Prognostic Biomarker in Gastrointestinal Stromal Tumor

Abstract

BackgroundPrognostic biomarkers are required for risk stratification therapy in the patients with gastrointestinal stromal tumor (GIST). In this study, we aimed to identify prognostic biomarkers in GIST. We assessed the prognostic value of E twenty-six variant 1 (ETV1), a recently identified transcription factor unique to GIST. We also examined the clinical utility and functions of its downstream gene, potassium channel tetramerization domain containing protein 10 (KCTD10).MethodsThe levels of ETV1 and KCTD10 were evaluated immunohistochemically in 112 patients with GIST treated at two hospitals. The functional properties of KCTD10 were examined by gene silencing assay in cultured GIST cells.ResultsImmunohistochemistry revealed that ETV1 expression in GIST had no prognostic significance. In contrast, the disease-free survival rate was 88.5% in patients with KCTD10-positive tumors and 55.8% in those with KCTD10-negative tumors (p <0.0001). KCTD10 was an independent prognostic factor (p <0.05). In the low-risk classification group, KCTD10 was significantly associated with favorable prognosis (p = 0.0008). Gene silencing of KCTD10 increased cell proliferation and invasion, suggesting that KCTD10 has a tumor-suppressive function.ConclusionsThe GIST-specific transcription factor ETV1 may have no prognostic potential, whereas its downstream gene KCTD10 is associated with a favorable prognosis. Our study indicated the novel prognostic utility of KCTD10 in GIST, and suggested its tumor-suppressive effects on GIST cells. Further validation studies of KCTD10 for clinical applications, and functional verification of KCTD10 for better understanding of molecular basis of malignant phenotypes are worth challenging in GIST.

KCTD10 Is Involved in the Cardiovascular System and Notch Signaling during Early Embryonic Development

“…Promoter analysis showed that KCTD10 can be regulated positively by SP1 and negatively by AP-2 transcription factors [5] . In a recent study, KCTD10 was reported to be regulated by a novel transcription factor ETV1 which is unique to gastrointestinal stromal tumors (GISTs), and RNAi-mediated silencing of KCTD10 increased cell invasion, suggesting that KCTD10 function as a tumor suppressor protein [7] . However, the exact functions of KCTD10 in mammalian development remain unclear.…”

SLITRK3 expression correlation to gastrointestinal stromal tumor risk rating and prognosis

“…However, it is very likely that there are other potential GIST risk-related genes, as suggested by our previous gene microarray (unpublished data). In agreement with this, the potassium channel tetramerization domain containing protein 10 (KCTD10) has been shown to correlate with GIST prognosis [31] . Future studies and identification of novel prognostic biomarkers will help further stratify risk groups and direct treatment strategies for GIST.…”

Clinical course of gastrointestinal stromal tumor diagnosed by endoscopic ultrasound‐guided fine‐needle aspiration

“…35 Kubota et al reported that ETV1 expression in GIST had no prognostic significance, but its downstream gene, KCTD10, was associated with a favorable prognosis in patients with GIST. 36 We also reported that GIST cases with DNA methylation, such as REC8, PAX3 and p16, had a poor prognosis. 37 The preoperative assessment of these biological markers may enable follow-up strategies for potentially lowmalignant GIST.…”