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An Immunosuppressive Status Classifier to Predict Recurrence and Assist in Decision Regarding Postoperative Adjuvant Treatment in Gastric Cancer
41 Pages Posted: 1 Jul 2021
More...Abstract
Background: Suppression of the immune microenvironment is a crucial cause of postoperative tumor recurrence. We constructed an immune infiltration classifier based on immunosuppressive indicators to predict recurrence and guide postoperative treatment for gastric cancer (GC).
Methods: Immunohistochemical analysis was performed for 825 GC tissues to evaluate immunosuppressive indicators. An immunosuppressive recurrence score (IRS) based on six immunosuppressive indicators was determined using the Lasso Cox method to predict recurrence outcomes. The association between immune infiltration and IRS was assessed using immunohistochemistry and multiplexed immunofluorescence staining. A nomogram predicting recurrence-free survival (RFS) was constructed by integrating IRS and significant clinicopathological features using the Cox regression model.
Results: The IRS and IRS-based nomogram showed remarkable accuracy and reliability for predicting the recurrence outcome. Moreover, elevated IRS was associated with locoregional recurrence and failure of postoperative adjuvant chemotherapy. We also identified that the increased IRS indicated the inhibition of anti-tumor effect of CD8+ tumor-infiltrating lymphocytes (TILs) in the invasive margin (IM).Conclusion: IRS can predict the recurrence outcome of GC patients by comprehensively distinguishing the immune infiltration status, which assists in the selection of different adjuvant treatment options.
Funding: the National Natural Science Foundation of China, the Science and Technology Innovation Joint Fund Project of Fujian Province.
Declaration of Interest: The authors have declared no conflicts of interest.
Ethical Approval: The study was approved by the Ethics Committees of Fujian Medical University Union Hospital, Affiliated Hospital of Qinghai University, and First Affiliated Hospital of
the University of Science and Technology of China. The ethics approval number of scientific research project is 2021KY018 from Fujian Medical University Union Hospital.
Keywords: Recurrence, Immunosuppressive indicators, Immune contexture, Adjuvant therapy, Gastric cancer
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