Novel immune-risk score of gastric cancer: A molecular prediction model combining the value of immune-risk status and chemosensitivity

Abstract

Gastric cancer is still one of the most common and deadly malignancies in the world. Not all patients could benefit from chemotherapy or chemoradiotherapy due to tumor heterogeneity. Therefore, identifying different subgroups of patients is an important trend for obtaining more effective responses. However, few molecular classifications associated with chemosensitivity are based on immune-risk status. In this study, we obtained six key immune-related genes. Using these genes, we constructed a molecular model related to immune-risk status and calculated an individual immune-risk score. The score showed great efficiency and stability in predicting prognosis and identifying different subgroups where persons could benefit from postoperative adjuvant therapy. The patients could be divided into different risk groups based on the immune-related score. For patients in the low-risk group, both postoperative chemoradiotherapy and chemotherapy could significantly improve prognosis on overall survival (OS) and disease-free survival (DFS) (DFS, P < 0.001 and P = 0.041, respectively; OS, P < 0.001, P = 0.006, respectively) and chemoradiotherapy was significantly superior than simple chemotherapy (DFS, P = 0.031; OS, P = 0.027). For patients with an intermediate-risk score, postoperative chemoradiotherapy showed a statistically significant survival advantage over no anticancer treatment (P = 0.004 and P = 0.002, respectively), while chemotherapy did not. Compared with no adjuvant treatment, neither postoperative chemoradiotherapy nor chemotherapy made significant difference for patients in the high-risk group. Combining the value of immune-risk status and chemosensitivity, the immune-risk score could not only offer us prognostic evaluation and adjuvant treatment guidance, but also improve our understanding about the binding point between chemotherapy or chemoradiotherapy and the immune system, which may be helpful for further expanding the application of immunotherapy.

Keywords: chemoradiotherapy and chemotherapy; gastric cancer; immune cell infiltration; immune-related genes; immune-risk status; molecular prediction model.