Identification of Circulating Biomarkers and Construction of a Prognostic Signature for Survival Prediction in Locally Advanced Pancreatic Cancer After Irreversible Electroporation

Abstract

Background Irreversible electroporation (IRE) is a novel treatment for locally advanced pancreatic cancer (LAPC), but the predictive factors, based on cytokines and immunocytes of survival, are still lacking. This study aimed to establish a risk model based on cytokines and immunocytes for LAPC patients undergoing IRE treatment. Patients and Methods Peripheral blood samples were obtained from 31 LAPC patients and 8 healthy control subjects before IRE. The phenotypes of lymphocytes were analyzed by flow cytometry, and the cytokines were evaluated with Luminex microarray assay. Least absolute shrinkage and selection operator (LASSO) and Cox regression were applied to assess the prognostic factors for overall survival (OS) and progression-free survival (PFS). A receiver operating characteristic (ROC) curve and a concordance index (C-index) were used to compare the abilities to predict survival rates. Results The relationship between multiple cytokines and clinical factors was evaluated and their prognostic value was compared. The five best predictors for OS and PFS, including CA19-9, CD3 + CD4 + T cells, CD3 + CD8 + T cells, IL-17A, and TNF-α were selected and incorporated into a new immune panel. A risk model based on this immune panel was established and exhibited significantly higher values of C-indexes and AUC for OS and PFS prediction as compared with tumor marker score and TNM stage system. Conclusion We presented a risk model based on a microarray assay of cytokines and lymphocytes for LAPC patients after receiving IRE treatment for the first time. The established risk model showed relatively good performance in survival prediction and was able to facilitate tailed patient management in clinical practice.

Irreversible Electroporation Plus Anti-PD-1 Antibody versus Irreversible Electroporation Alone for Patients with Locally Advanced Pancreatic Cancer

“…Thus, apart from inducing apoptosis of tumor cells, IRE can also reconstruct the microenvironment within the tumor and induce the immune response. [9][10][11] Previous studies had shown that IRE could alleviate immune suppression and induce activation of T cells, indicating that IRE may potentiate the antitumor efficacy of immunotherapy in PDAC. 9,12 In recent years, game-changing advances have been achieved in the development of therapies of various cancers, including melanoma, lung and liver cancers with immune checkpoint inhibitors (ICIs).…”