Supplementary Material for: Downregulation of SIRT4 Expression Is Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma

<b><i>Objective:</i></b> SIRT4, a mitochondria-localized sirtuin, represses glutamine metabolism by inhibiting glutamate dehydrogenase (GDH). The current study aimed to evaluate the clinical and biological significance of SIRT4 in esophageal squamous cell carcinoma (ESCC). <b><i>Methods:</i></b> The study comprised 172 patients with surgically resected ESCC in two independent cohorts. <i>SIRT4</i> mRNA expression was analyzed in Cohort 1 (n = 79) and SIRT4 protein expression in Cohort 2 (n = 93). The association of SIRT4 expression with clinicopathological parameters and prognosis was assessed. Furthermore, the biological role of SIRT4 in ESCC cell lines was examined. <b><i>Results:</i></b> SIRT4 expression was not correlated with any clinicopathological parameters in both cohorts. In Cohort 1, low-<i>SIRT4</i>-expression cases had poorer overall survival than high-<i>SIRT4</i>-expression cases (p = 0.016). In Cohort 2, SIRT4-negative cases had poorer overall survival and disease-free survival than SIRT4-positive cases (p = 0.011 and 0.0026). Multivariate analysis revealed that SIRT4 expression was an independent prognostic factor for overall survival (HR = 2.06, p = 0.038). The rate of distant recurrence was significantly higher in SIRT4-negative cases than in SIRT4-positive cases (39.4 vs. 7.4%; p = 0.0023). In vitro, <i>SIRT4</i> knockdown significantly increased GDH activity and promoted cell proliferation and migration. <b><i>Conclusion:</i></b> SIRT4 is a potential prognostic biomarker in ESCC

Supplementary Material for: Clinicopathological Characteristics, Surgery and Survival Outcomes of Patients with Duodenal Gastrointestinal Stromal Tumors

<i>Background:</i> Duodenal gastrointestinal stromal tumors (GISTs) are a rare subset of GISTs (3-5%), and their clinicopathological features have not been fully described. The purpose of this retrospective study was to examine these characteristics and compare the operative procedures. <i>Methods:</i> Twenty-five patients with duodenal GIST underwent complete resection, local resection (LR) or pancreaticoduodenectomy (PD) from 1990 to 2014 at our 2 hospitals. We analyzed patient characteristics, treatments, histological examinations, postoperative complications and survival outcomes. <i>Results:</i> Twelve patients (48%) with no symptoms were incidentally diagnosed for unrelated reasons. Sixteen patients (64%) had c-<i>kit</i> mutations while 6 (24%) were wild-type, including 4 with a history of neurofibromatosis type 1. Comparing LR (n = 16) and PD (n = 9), the recurrence-free survival rate was significantly worse for PD. On multivariate analysis, however, tumor size was an independent and significant prognostic factor, but not operative procedure. There was no body weight change with LR, but body weight decreased by 7% with PD.<i>Conclusion:</i> Duodenal GISTs had different characteristic genetic mutations compared to other GISTs. LR for duodenal GISTs appears to be oncologically and nutritionally feasible