Immune-infiltration based signature as a novel prognostic biomarker in gastrointestinal stromal tumour
Zhe-Wei Wei,
Jing Wu,
Wei-Bin Huang,
Jin Li,
Xiao-Fang Lu,
Yu-Jie Yuan,
Wen-Jun Xiong,
Xin-Hua Zhang,
Wei Wang,
Yu-Long He,
Chang-Hua Zhang
Affiliations
Zhe-Wei Wei
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China
Jing Wu
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China; Center of Digestive Diseases, The Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, Guangdong 518000, China
Wei-Bin Huang
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China
Jin Li
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China; Center of Digestive Diseases, The Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, Guangdong 518000, China
Xiao-Fang Lu
Department of Pathology, The Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, Guangdong 518000, China
Yu-Jie Yuan
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China
Wen-Jun Xiong
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong 510120, China
Xin-Hua Zhang
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China
Wei Wang
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong 510120, China
Yu-Long He
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China; Center of Digestive Diseases, The Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, Guangdong 518000, China; Corresponding authors.
Chang-Hua Zhang
Center of Digestive Diseases, The Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, Guangdong 518000, China; Corresponding authors.
Background: Accumulating evidence indicates that tumour-infiltrating lymphocytes (TILs) are the primary determinant of survival outcomes in various tumours. Thus, we sought to investigate the TIL distribution and density in gastrointestinal stromal tumours (GISTs) and to develop an immune infiltration (II)-based signature to predict prognosis. Methods: The expression of 8 immune features in the tumour centre (TC) and tumour margin (TM) and PD-L1 in 435 GIST patients was investigated by immunohistochemistry. Then, a 4-feature-based II-GIST signature integrating the CD3+ TC, CD3+ TM, CD8+ TM and CD45RO+ TM parameters was developed using a LASSO Cox regression model in the training cohort and was validated in two separate validation cohorts. Findings: High CD3+ TC, CD3+ TM, CD8+ TC, CD8+ TM, CD45RO+ TM, NKp46+ TM and CD20+ TM correlated with improved survival. Patients with high II-GIST scores have better RFS and OS outcomes than those with low II-GIST scores. Multivariable analyses demonstrated that the II-GIST signature is an independent prognostic factor. The receiver operating characteristic (ROC) curve demonstrated that the prognostic accuracy of the II-GIST signature is superior to that of the NIH risk criteria. Further analysis showed that moderate- and high-risk GIST patients with high II-GIST scores could gain survival benefits from adjuvant imatinib therapy. Interpretation: The novel II-GIST signature accurately predicted the survival outcomes of GIST patients. In addition, the II-GIST signature was a useful predictor of survival benefit from imatinib therapy amongst moderate- and high-risk patients with GIST. Funding: This project was supported by National Natural Science Foundation of China (81702325), Natural Science Foundation of Guangdong Province (2017A030310565), and 3&3 Project of the First Affiliated Hospital of Sun Yat-sen University.