Clinical relevance of CD70 expression in resected pancreatic cancer: Prognostic value and therapeutic potential

• DOI: 10.1016/j.pan.2021.01.013
• Publication Date: 2021-01-25T06:57:05Z
• Authors: Kota Nakamura; Masayuki Sho; Takahiro Akahori; Satoshi Nishiwada; Tomohiro Kunishige; Kenji Nakagawa; Minako Nagai; Tadataka Takagi; Taichi Terai; Naoya Ikeda
• Keywords: Adult; Aged, 80 and over; Male; Antineoplastic Agents; Middle Aged; Prognosis; Real-Time Polymerase Chain Reaction; Deoxycytidine; 3. Good health; Pancreatic Neoplasms; 03 medical and health sciences; Pancreatectomy; 0302 clinical medicine; Cell Movement; Chemotherapy, Adjuvant; Cell Line, Tumor; Biomarkers, Tumor; Humans; Female; Aged; CD27 Ligand; Carcinoma, Pancreatic Ductal; Cell Proliferation

Abstract BackgroundAberrant expression of CD70 in several malignancies is potentially associated with poor patient prognosis and could serve as a therapeutic target. However, the clinical relevance of CD70 expression in pancreatic cancer has not been thoroughly explored.MethodsWe evaluated CD70 expression in 166 surgical specimens obtained from human patients with pancreatic cancer. We analyzed the function of CD70 in proliferation and migration using pancreatic cancer cell lines with silenced CD70 expression.ResultsCD70 expression was positively stained in 42 patients (25%). In the whole cohort, high CD70 expression was not associated with overall survival (OS: 33.1 vs. 40.8 months, P = 0.256), although it was significantly associated with inferior OS in a population of patients that completed adjuvant chemotherapy (P = 0.027). Moreover, the incidence of hematogenous metastasis was significantly higher in patients with high CD70 expression than in those with low CD70 expression (P = 0.020). This finding was also statistically significant in multivariate analyses (P = 0.001). In vitro experiments demonstrated that CD70 expression contributed to cancer cell proliferation independently of gemcitabine treatment as well as cell migration. Furthermore, real-time polymerase chain reaction analysis of frozen surgical tissues showed a correlation between the expression of CD70 and mesenchymal markers.ConclusionsCD70 expression in pancreatic cancer might be involved in hematogenous metastasis. Furthermore, our results imply that CD70 overexpression can serve as a novel prognostic factor and a potential therapeutic target in patients who have completed adjuvant chemotherapy.