Immune-Infiltration Based Signature As a Novel Prognostic Biomarker in Gastrointestinal Stromal Tumor

Abstract

Background: Accumulating evidence showed that tumor-infiltrating lymphocytes (TILs) are dominant determinants of survival outcomes in various kinds of tumors. Thus, we sought to investigate the distribution and density of TILs in gastrointestinal stromal tumors (GISTs), and develop an immune-infiltration (II) based signature to predict prognosis. Methods: The expression of 7 immune features was investigated by immunohistochemistry from 435 GIST patients in tumor center (TC) and margin (TM), respectively. Then, a 4-feature-based II-GIST signature was constructed using the LASSO Cox regression model in the training cohort and validated in another two validation cohorts. The II-GIST signature integrated CD3+ TC, CD3 + TM, CD8+ TM and CD45RO+ TM. Results: High CD3+, CD8+, CD45RO+, NKp46+ and CD20+ infiltrations, in TC or TM correlated with improved recurrence-free survival (RFS) and overall survival (OS). Kaplan-Meier analysis and the log rank test suggested that high II-GIST patients experience better RFS and OS. Multivariate analyses demonstrated that II-GIST signature is an independent prognostic factor. When stratified by tumor size, mitotic index, National Institutes of Health (NIH) risk categories and primary tumor location, II-GIST remained to be an efficient prognostic model. The receiver operator characteristic (ROC) curve demonstrated that the prognostic accuracy of II-GIST signature is superior to that of NIH risk categories. Further analysis demonstrated that moderate and high risk GIST patients with high II-GIST could gain survival benefits from adjuvant imatinib therapy. Conclusion: The novel II-GIST signature could accurately predict the survival outcomes of GIST patients. In addition, the II-GIST signature was a useful predictor for survival benefit from imatinib therapy among moderate and high risk GISTs. Funding Statement: This study was supported by National Natural Science Foundation of China, No. 81702325; Natural Science Foundation of Guangdong Province, No. 2017A030310565; 3&3 Project of the First Affiliated Hospital of Sun Yat-sen University. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University and the Second Affiliated Hospital of Guangzhou University of Chinese Medicine.