Development and Validation of Tumor-Infiltrating Lymphocyte Score for Predicting the Prognosis of Patients with Gastric Cancer

Background: Gastric cancer (GC) is the fifth most common cancer worldwide. Tumor-infiltrating lymphocytes (TILs) are associated with development and progression of GC, and maybe a prognostic biomarker. Methods: We determined the expression of CD3+, CD4+, CD8+, CD20+, CD57+, and Foxp3+ TILs in tissue microarrays of 475 GC tissues by immunohistochemistry. Lymphocyte features and their ratios were used to build a multimarker TIL-Score by LASSO logistic regression. Chi-square tests and Kaplan-Meier estimation was performed to validate the efficiency of the TIL-Score for predicting GC prognosis. A nomogram and decision curve were prepared for guiding clinical decisions. Finding: Ten individual TIL factors were integrated into the TIL-Score by LASSO logistic regression. The clinicopathological analysis showed that the TIL-Score was correlated with tumor size, tumor invasion, lymph node metastasis, and lower TNM stage in the primary and validation cohorts. Patients in the high TIL-Score group had significantly higher overall survival and disease-free survival rates than patients in the low TIL-Score group in both the primary and validation cohorts. In the TIL nomogram based on independent prognostic factors, receiver operating characteristic analysis showed that the area under the curve values were 0.825 and 0.800 in the primary and validation cohorts, respectively. Decision curve analysis demonstrated that the TIL nomogram was clinically useful. Interpretation: Overall, we developed a multimarker TIL-Score and TIL nomogram useful for predicting the prognosis of patients with GC. Funding Statement: National Natural Science Foundation of China(31670922, 81672707 and 81602165), Natural Science Foundation of Zhejiang(YLQ16H190003), Wenzhou Science and Technology Bureau(Y2017002). Declaration of Interests: The authors report no conflict of interest. Ethics Approval Statement: The study was approved by the Research Ethics Committee of The Second Affiliated Hospital of Wenzhou Medical University. All subjects provided written informed consent.