Abstract
Abstract Background: Mucin1 (MUC1) is a glycoprotein as a member of the mucin family. The expression has been associated with poor prognosis in patients with several types of cancer. Duodenal cancer is rare, therefore details are not known including carcinogenesis and clinical treatment. We verify the association of MUC1 expression and prognosis in patient with duodenal adenocarcinoma. We also assess the function of MUC1 in vitro. Materials and Methods: Between 1989 and 2014, eighteen patients of duodenal adenocarcinoma with surgery at Jichi Medical University Hospital were included in this study. MUC1 expression was evaluated immunohistochemically with anti-MUC1 antibody to examine the association of MUC1 expression and prognosis clinicopathologically. A human-derived duodenal cancer cell line, HuTu-80, is used for the experiments of invasiveness and proliferation in vitro. The invasive capacity was evaluated by transfection of siRNA into HuTu80 with matrigel invasion assay. Viability assay with the anti-MUC1 peptide GO201 was assessed to determine whether MUC1 associate with cell growth of duodenal adenocarcinoma. Results: Seven cases were MUC1 positive and 11 were MUC1 negative immunohistochemically. TMN staging was not associated with MUC1 expression. Kaplan-Meir analysis showed a poor prognosis with MUC1 positive patients in cumulative overall survivals (MUC1 positive : MUC1 negative, 18M : 52M; HR:20.6, 95%CI 3.247-130.7,p=0.002). Lymph node metastasis of MUC1 positive patients (71.4%) was significantly higher than MUC1 negative patients (9%) (p = 0.01). In vitro experiment, the expression of MUC1 was confirmed by RT-PCR and flowcytometry. Knockdown experiment with transduction of siRNAs to HuTu80 decreased the expression of the MUC1 gene. Transduction of siRNAs significantly reduced invasive capacity (47.02±21.65%, 95%CI 3.046-102.9, p= 0.04). Growth of HuTu80 cells was inhibited by GO201 (5 μM : 95%CI 0.109-0.3565, 10μM :95%CI 0.024-0.389 p<0.0001). Conclusions: MUC1 expression is a predictive marker for poor prognosis in patients with duodenal adenocarcinoma. Functional Interference of MUC1 core protein reduces cell growth and invasiveness. Taken together, MUC1 is associated with malignant potential and a novel target for the treatment. Citation Format: Satomi Shiba, Atsushi Miki, Hideyuki Ohzawa, Takumi Teratani, Yasunaru Sakuma, Joji Kitayama, Alan Kawarai Lefor, Naohiro Sata. MUC1 expression as a prognosis marker and a new therapeutic target in patient with duodenal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3140. doi:10.1158/1538-7445.AM2017-3140
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