RESUMO
BACKGROUND: Endoscopic therapy (ET) of gastrointestinal stromal tumors (GIST) has become a viable treatment. We intended to compare long-term outcomes of ET versus surgical resection for 2-5 cm GIST using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A multicenter retrospective study was conducted to compare the long-term outcomes of patients treated with ET and surgical resection for GIST. The multivariate Cox proportional hazards models were used to identify predictors for patients survival. To balance the clinicopathologic characteristics, a 1:1 propensity score matching (PSM) was utilized. RESULTS: A total of 749 patients with 2-5 cm GIST were enrolled, of whom 113 accepted ET and 636 underwent surgical resection. Before PSM, there was no significant difference in long-term outcomes between ET and surgical resection (5-year overall survival (OS): 93.5% vs. 91.6%, P=0.374; 5-year cancer-specific survival (CSS): 99.1% vs. 96.5%, P=0.546; 10-year OS: 71.1% vs. 78.2%, P=0.374; 10-year CSS: 93.6% vs. 92.7%, P=0.546). After adjusting for the relevant variables using the multivariable Cox proportional hazards models, we observed that the ET and surgical resection groups were similar in OS (HR 0.726, 95%CI 0.457-1.153, P=0.175) and CSS (HR 1.286, 95%CI 0.474-3.488, P=0.621). After PSM, the long-term OS and CSS of patients with 2-5 cm GIST after ET and surgical resection were comparable. CONCLUSIONS: We found that the long-term survival of patients with 2-5 cm gastric GIST after ET and surgical resection were comparable. Further high-quality studies are needed to confirm the role of ET in 2-5 cm GIST.
RESUMO
As an important regulator of intracellular protein degradation, the mechanism of the deubiquitinating enzyme family in tumour metastasis has received increasing attention. Our previous study revealed that USP3 promotes tumour progression and is highly expressed in gastric cancer (GC). Herein, we report two critical targets, COL9A3 and COL6A5, downstream of USP3, via the isobaric tags for relative and absolute quantification technique. Mechanistically, we observed that USP3 interacted with and stabilised COL9A3 and COL6A5 via deubiquitination in GC. Importantly, we found that COL9A3 and COL6A5 were essential mediators of USP3-modulated oncogenic activity in vitro and in vivo. Examination of clinical samples confirmed that elevated expression of USP3, concomitant with increased COL9A3 and COL6A5 abundance, correlates with human GC progression. These data suggest that USP3 promotes GC progression and metastasis by deubiquitinating COL9A3 and COL6A5. These findings identify a mechanism of GC metastasis regarding USP3-mediated deubiquitinating enzyme activity and suggest potential therapeutic targets for GC management.
