Abstract
Gallbladder cancer is a relatively uncommon human malignant tumor with an extremely poor prognosis. Currently, no biomarkers can accurately diagnose gallbladder cancer and predict patients’ prognosis. XRCC1 is involved in tumorigenesis, progression, and chemo-resistance of several human cancers, but the role of XRCC1 in gallbladder cancer is never reported. In this study, we investigated the expression of XRCC1 and its clinicopathological and prognostic significance in gallbladder cancer, and explored the biological role of XRCC1 in gallbladder cancer cells. We found that XRCC1 was significantly up-regulated in gallbladder cancer in protein and mRNA levels. Positive XRCC1 expression was correlated with aggressive clinicopathological features and was an independent poor prognostic factor in gallbladder cancer. The ROC curves suggested that XRCC1 expression had potential clinicopathological diagnostic value in gallbladder cancer. In vitro, XRCC1 was overexpression in CD133+GBC-SD cells compared to GBC-SD cells. In functional experiment, XRCC1 knockdown had a non-significant impact on proliferation, migration, invasion, and apoptosis of CD133+GBC-SD cells. But, XRCC1 knockdown could significantly improve the sensitivity of CD133+GBC-SD cells to 5-Fluorouracil via promoting cell necrosis and apoptosis. Thus, this study indicates that XRCC1 may be a promising predictive biomarker of gallbladder cancer and a potential therapeutic target for gallbladder cancer.
Highlights
Gallbladder cancer (GBC) is a relatively uncommon human malignant tumor with an extremely poor prognosis
Previous studies reported that both x-ray repair cross-complementing group 1 (XRCC1) and CD133+cancer cells are related to tumor drug resistance so that we studied the role of XRCC1 in CD133+GBC-SD cells
Compared with GBC-SD cells, XRCC1 mRNA and protein were overexpressed in CD133+GBC-SD cells (Figure 2). These results indicated that XRCC1 might affect the unique biological features of CD133+GBC-SD cells compared to normal GBC-SD cells, such as chemo-resistance
Summary
Gallbladder cancer (GBC) is a relatively uncommon human malignant tumor with an extremely poor prognosis. Various studies about GBC were performed, GBC clinical outcome remains extremely poor. Radical resection remains the only way to cure XRCC1 in GBC. GBC, adjuvant treatments (chemotherapy and radiotherapy) are available. GBC is often resistant to chemotherapy and radiotherapy (Horgan et al, 2012). These above reasons make the prognosis of GBC unsatisfactory.
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