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

Pancreatology. 2021 Apr;21(3):573-580. doi: 10.1016/j.pan.2021.01.013. Epub 2021 Jan 25.

Abstract

Background: Aberrant 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.

Methods: We 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.

Results: CD70 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 (OS: 45.4 vs. 63.8 months, 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.

Conclusions: CD70 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.

Keywords: Chemotherapy; Metastasis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • CD27 Ligand / metabolism*
  • Carcinoma, Pancreatic Ductal / drug therapy
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / surgery*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chemotherapy, Adjuvant
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Pancreatectomy*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / surgery*
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Survival Analysis

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CD27 Ligand
  • CD70 protein, human
  • Deoxycytidine
  • Gemcitabine