Abstract
Gallbladder Cancer (GBC), characterized by invasive growth and infiltrative dissemination, is difficult to diagnose and has poor prognosis. Emerging evidence demonstrates that Lysine-Specific Demethylase 1 (LSD1) has important roles in carcinogenesis, proliferation and metastasis. We studied the roles and molecular mechanisms of LSD1 in GBC. We examined LSD1 expression in 109 paired samples of GBC and normal gallbladder tissues. We found GBC tissues had upregulated LSD1 compared with normal gallbladder tissues (P = 0.003), and its high expression was associated with tumor-node-metastasis stage (P < 0.0001), Nevin's stage (P = 0.0093) and distant metastases (P = 0.0070). We found positive correlations between LSD1 expression and other proteins: epithelial-mesenchymal transition markers, C-myc and cyclin-related proteins. Inhibiting LSD1 expression in vitro impaired the proliferation and invasiveness of GBC cells and also downregulated c-myc expression and consequently inhibited GBC cell proliferation. LSD1 overexpression promotes GBC development and may be a predictor for a worsened prognosis. LSD1 may be a novel therapeutic target and prognostic tool for gallbladder cancer.
Highlights
As the fifth most common biliary tract malignancy, Gallbladder Cancer (GBC) has always been associated with high mortality and poor prognosis worldwide [1, 2]
We found that patients with GBC and lower Lysine-Specific Demethylase 1 (LSD1) expression had better overall survival after surgery, suggesting that LSD1 expression is associated with poor prognosis in patients with GBC (Fig. 2B)
To determine whether LSD1 levels are related to GBC progression, we analyzed the association between LSD1 and clinicopathologic status in GBC patients of 109 paired cDNA samples
Summary
As the fifth most common biliary tract malignancy, Gallbladder Cancer (GBC) has always been associated with high mortality and poor prognosis worldwide [1, 2]. In most countries the prognosis of GBC is extremely poor, with a 5-year survival rate of 5%–10% and median survival of only 3–6 months from the time of diagnosis [5] This phenomenon is largely due to the anatomical position of the gallbladder and the high proportion of tumors that are advanced at the time of presentation. As an oncogenic transcription factor, the C-myc protein recognizes the E-box recognition site and several related, non-canonical sequences in the promoter regions of target genes [9]. These targets affect a wide array of biological functions in different cellular models, such as cell differentiation and metastasis. We found that C-myc has a tight relationship with Lysine-Specific Demethylase 1 (LSD1), which is located downstream in the gene sequence
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
